@article {pmid42079230,
year = {2026},
author = {Lai, HY and Yoo, Y and Tjaernberg, A and Li, R and He, Z and Travaglini, KJ and Qiao, Q and Agrawal, A and Kana, O and van Velthoven, C and Carroll, JB and Gillespie, M and Mukherjee, S and Fardo, DW and Li, XJ and Lein, E and Gabitto, MI},
title = {scVIP: personalized modeling of single-cell transcriptomes for developmental and disease phenotypes.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.04.20.717759},
pmid = {42079230},
issn = {2692-8205},
abstract = {Single-cell transcriptomics resolves cellular heterogeneity within individuals, but connecting molecular states to individual-level phenotypes requires frameworks that explicitly bridge these scales. We present scVIP, a generative model that links gene expression, cell-type composition, and phenotypic measurements within a single probabilistic model, which enables accurate phenotype prediction and interpretable trajectory inference. A cell-type-aware multi-instance learning architecture learns donor embeddings that capture progression while localizing phenotype-associated signals to specific cell populations. Applied across four settings, scVIP accurately predicts cortical developmental age (Pearson r = 0.95), characterizes Huntington's disease progression (concordance correlation coefficient = 0.90), integrates two Alzheimer's disease cohorts recovering disease-relevant microglial and astrocytic programs, and distinguishes healthy from ACPA-positive individuals and non-progressors from early RA individuals, identifying inflammatory T cell programs associated with disease. scVIP enables principled analysis of how cellular states collectively shape organism-level phenotypes across development and disease.},
}

@article {pmid42378088,
year = {2026},
author = {Yang, T and Xu, YR and Li, S and Bellier, JP and Tao, Y and Francis, AE and Stern, AM and Jin, S and Ostaszewski, BL and Lawton, TL and Pradier, L and Reczek, D and Lemere, CA and Walsh, DM and Selkoe, DJ},
title = {Immunotherapy with B28, an antibody to Aβ oligomers, potently decreases amyloid plaques, microgliosis, and memory decline in APP knock-in mice.},
journal = {Cell reports},
volume = {45},
number = {7},
pages = {117599},
doi = {10.1016/j.celrep.2026.117599},
pmid = {42378088},
issn = {2211-1247},
abstract = {Immunotherapy against amyloid β-protein (Aβ) for Alzheimer's disease (AD) has been widely approved. Breakthrough disease-modifying treatments such as lecanemab and donanemab are often followed by drugs with improved efficacy. By immunizing Trianni mice with aggregated synthetic Aβ, we obtained B28, a fully human antibody specifically selected for its neutralization of tau neuritic dystrophy induced by AD brain-derived oligomers. In a blinded trial in mutant human APP[NL-G-F] knock-in mice, weekly infusions of B28 for four months markedly reduced both amyloid plaques and Aβ oligomers, attenuated plaque-associated astrocytosis and microgliosis, preserved neurons, and lessened memory decline. Biochemical and histological analyses showed that B28 engaged both plaque-bound and diffusible Aβ, forming immune complexes and depleting free Aβ. In in vitro immunoassays, B28 had significantly higher affinity and captured more Aβ from AD brain extracts than did lecanemab. B28 is a potent, aggregate-preferring Aβ antibody that clears plaques and decreases gliosis, supporting its clinical development.},
}

@article {pmid42378151,
year = {2026},
author = {Espis, A and Marzi, C and Diciotti, S},
title = {NeuroBooster: a domain-informed self-supervised learning paradigm tailored for brain MRI analysis.},
journal = {IEEE journal of biomedical and health informatics},
volume = {PP},
number = {},
pages = {},
doi = {10.1109/JBHI.2026.3708015},
pmid = {42378151},
issn = {2168-2208},
abstract = {Self-supervised learning (SSL) has demonstrated its potential to reduce reliance on labeled data and improve generalization to independent test sets compared to traditional supervised learning (SL). However, current SSL paradigms are predominantly designed as domain-agnostic and are often evaluated on benchmark datasets like ImageNet. As already shown in other studies, SSL paradigms tailored for the medical domain can outperform domain-agnostic SSL paradigms. This study introduces NeuroBooster, a paradigm tailored for brain MRI analysis. Its core idea is to leverage automated feature extraction tools to generate anatomical features, which are then used as targets in a regression pretext task. The paradigms were evaluated and compared on a regression task, i.e., age prediction, and a classification task, i.e., the discrimination between patients with Alzheimer's disease and cognitively normal subjects. Each pre-training and fine tuning experiment was repeated across 30 randomized seeds to estimate the uncertainty, while enabling full reproducibility. Our results revealed NeuroBooster's superiority across various scenarios. Notably, with only 1% of labeled data available, NeuroBooster achieved an average mean absolute error of 5.67 years smaller than SL. These findings demonstrate NeuroBooster's efficacy and highlight its potential within brain MRI analysis, suggesting a promising direction for developing specialized SSL paradigms in this domain.},
}

@article {pmid42378300,
year = {2026},
author = {Nihat, A and Arora, P and Schmidt, C and Rayner, MLD and Linehan, J and Brandner, S and Mead, S and Collinge, J and Jat, PS},
title = {A scalable, dividing cell model for the robust propagation and quantification of human sporadic Creutzfeldt-Jakob disease prions.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {123},
number = {27},
pages = {e2600341123},
doi = {10.1073/pnas.2600341123},
pmid = {42378300},
issn = {1091-6490},
support = {MR/P019862/1//UKRI | Medical Research Council (MRC)/ ; },
mesh = {Humans ; *Creutzfeldt-Jakob Syndrome/pathology/metabolism ; Animals ; Mice ; *Prions/metabolism ; Disease Models, Animal ; Brain/pathology/metabolism ; Biological Assay/methods ; Mice, Transgenic ; Models, Biological ; },
abstract = {Prion diseases represent a unique biological paradigm with mechanistic parallels to other neurodegenerative conditions like Alzheimer's and Parkinson's diseases. However, the study of human prion pathobiology and the development of effective therapeutics has been severely constrained by the inability to propagate human prions in dividing cells-forcing reliance on costly and slow animal bioassays. Here, we report the generation of EKV cells-a humanized cell model which supports the robust, indefinite propagation of sporadic Creutzfeldt-Jakob disease (sCJD) prions. We demonstrate that these cells replicate bona fide human prion infectivity in culture-cell lysates induce lethal neurodegeneration in humanized mice that is clinically and neuropathologically indistinguishable from inoculation with sCJD-infected brain tissue. We use EKV cells to develop the Human Prion Assay (HPA), which quantifies sCJD infectivity with sensitivity comparable to gold-standard mouse bioassay, while reducing the experimental timeline from years to weeks. Furthermore, we demonstrate that established sCJD infection can be cured by an anti-prion protein antibody, validating the system as a high-throughput platform for drug discovery. This model bridges a critical translational gap, offering a renewable alternative to animal bioassays, a paradigm to dissect the biology of human sCJD prion disease and screen for therapeutic agents.},
}

Humans
*Creutzfeldt-Jakob Syndrome/pathology/metabolism
Animals
Mice
*Prions/metabolism
Disease Models, Animal
Brain/pathology/metabolism
Biological Assay/methods
Mice, Transgenic
Models, Biological

@article {pmid42378334,
year = {2026},
author = {Hafeez, AS and Mumtaz, S and Kumar, L and Amir, M and Maity, R and Ashraf, S and Khan, A and Hassan, M and Zaman, A and Asad, M and Singh, P and Faisal, AR and Dhali, A},
title = {Nationwide trends and forecasts in Alzheimer's and cerebrovascular disease-related mortality in the United States, 1999-2023: A CDC WONDER analysis.},
journal = {The Journal of international medical research},
volume = {54},
number = {6},
pages = {3000605261454837},
doi = {10.1177/03000605261454837},
pmid = {42378334},
issn = {1473-2300},
mesh = {*Alzheimer Disease/mortality ; Humans ; United States/epidemiology ; *Cerebrovascular Disorders/mortality ; Female ; Aged ; Male ; Retrospective Studies ; Aged, 80 and over ; Centers for Disease Control and Prevention, U.S. ; Forecasting ; Mortality/trends ; },
abstract = {ObjectiveTo describe nationwide mortality patterns related to Alzheimer's disease and cerebrovascular disease in United States adults aged ≥65 years and explore future trend projections.MethodsIn this retrospective study, we utilized the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research database (ICD-10 G30, I60-I69) to calculate crude and age-adjusted mortality rates per 100,000 population. Temporal trends were modeled using Joinpoint regression, and 10-year forecasts were obtained using autoregressive integrated moving average models. Subgroup analyses were performed by sex, race/ethnicity, census region, urbanization, and place of death.ResultsWe identified 199,606 Alzheimer's disease-cardiovascular disease-related deaths. Overall, age-adjusted mortality rates peaked at 24.8 in 2002, reduced to 14.2 in 2013, and then rose to 18.7 in 2020 before dropping to 16.6 in 2023. Women exhibited higher age-adjusted mortality rates than men (20.1 vs. 16.0). Individuals of White and Black ethnicity bore the greatest burden, and the South and West recorded the highest regional age-adjusted mortality rates. These rates were consistently higher in non-metropolitan areas than in metropolitan areas. Exploratory projections estimate an overall age-adjusted mortality rate of 16.6 by 2033, with persistently higher rates in women, non-Hispanic Black populations, and among those residing in the West and non-metropolitan areas.ConclusionsDespite substantial decline since the early 2000s, Alzheimer's disease-cardiovascular disease mortality remains high and unevenly distributed. Exploratory projections suggest that the burden will remain substantial, underscoring the need for targeted prevention, vascular risk reduction, and equity-focused dementia care.},
}

*Alzheimer Disease/mortality
Humans
United States/epidemiology
*Cerebrovascular Disorders/mortality
Female
Aged
Male
Retrospective Studies
Aged, 80 and over
Centers for Disease Control and Prevention, U.S.
Forecasting
Mortality/trends

@article {pmid42378690,
year = {2026},
author = {El Wahab, MMA and Saad, S and El-Enany, N and Sheribah, ZA},
title = {A Sustainable Spectrofluorimetric Quenching Approach for Determination of Pentoxifylline or Donepezil HCl via Complexation With Erythrosine B: Application to Tablets and Human Plasma.},
journal = {Luminescence : the journal of biological and chemical luminescence},
volume = {41},
number = {7},
pages = {e70542},
doi = {10.1002/bio.70542},
pmid = {42378690},
issn = {1522-7243},
support = {//The Science, Technology & Innovation Funding Authority (STDF)/ ; //The Egyptian Knowledge Bank (EKB)/ ; },
mesh = {Spectrometry, Fluorescence/methods ; *Pentoxifylline/blood/analysis ; Humans ; Donepezil ; *Erythrosine/chemistry ; Tablets/analysis ; *Indans/blood/analysis ; *Piperidines/blood/analysis ; },
abstract = {This work introduces a novel, green switch on-off spectrofluorimetric quenching method using erythrosine B (EB) for nano-trace determination of pentoxifylline (PTX) or donepezil HCl (DPZ) in tablets and spiked plasma, enabling rapid clinical monitoring. The suggested approach relies on the quenching effect of either DPZ or PTX on the intrinsic fluorescence of EB, various experimental conditions influencing fluorescence quenching were investigated and optimized. An ion pair complex is formed between the cationic amino group in either drugs and the anionic phenolic group of EB at mild acidic conditions using Britton-Robinson buffer. After excitation at 528 nm, the fluorescence quenching intensities were measured linearly at 552 nm across the range (50-1000 ng/mL) for PTX with quantification limits of 16.76 ng/mL and over the range (20-500 ng/mL) for DPZ with limit of quantification 17.56 ng/mL for DPZ. The suggested method exhibited high % recoveries, confirming its reliable applicability in complicated matrices. The validation of the suggested methodology was further performed in accordance with the International Conference of Harmonization (ICH Q2R2) recommendations. Furthermore, the method's greenness, blueness and whiteness profiles was investigated, revealing its remarkable sustainability.},
}

Spectrometry, Fluorescence/methods
*Pentoxifylline/blood/analysis
Humans
Donepezil
*Erythrosine/chemistry
Tablets/analysis
*Indans/blood/analysis
*Piperidines/blood/analysis

@article {pmid42378963,
year = {2026},
author = {Li, C and Tambo, W and Powell, K and Giliberto, L and Sciubba, D},
title = {Endogenous neuroprotection in vascular cognitive impairment and dementia.},
journal = {EBioMedicine},
volume = {129},
number = {},
pages = {106357},
doi = {10.1016/j.ebiom.2026.106357},
pmid = {42378963},
issn = {2352-3964},
abstract = {Vascular cognitive impairment and dementia (VCID), affecting millions globally with 30% higher mortality than Alzheimer's disease, lacks effective pharmacotherapies. Microvascular dysfunction emerges decades before clinical symptoms, driving irreversible neurodegeneration once established. Clinical results show that nonpharmacologic interventions demonstrate greater effectiveness: three-fold greater cognitive improvement and five-fold enhanced functional outcomes versus pharmacotherapy, while avoiding adverse effects that affect 40% of patients receiving pharmacological treatments. These interventions orchestrate convergent mechanisms: vascular restoration (reversing vasoconstriction, augmenting perfusion), metabolic reprogramming (mitochondrial/glucose optimisation), neuroinflammation resolution, oxidative stress mitigation, and synaptic preservation. Exercise, neuromodulation, dietary modification, environmental enrichment and conditioning medicine activate multilevel endogenous repair mechanisms inaccessible to pharmacological targeting. This review presents a comprehensive mechanistic framework elucidating how nonpharmacologic strategies modulate interconnected vascular/non-vascular domains. It highlights emerging bioelectronic medicine as a promising disease-modifying therapy, establishing nonpharmacologic interventions as first-line strategies that reconceptualize VCID from intractable neurodegeneration to a preventable, potentially reversible, condition.},
}

@article {pmid42379016,
year = {2026},
author = {Yi, Z and Yao, Z and Wang, F and Xu, M and Deng, C and Yao, W and Chen, X and Shi, J and Liu, F and Dong, W and Wang, X},
title = {Ribavirin mitigates Alzheimer's disease model phenotypes by enhancing lysosomal function and suppressing ISR.},
journal = {Bioorganic chemistry},
volume = {180},
number = {},
pages = {110142},
doi = {10.1016/j.bioorg.2026.110142},
pmid = {42379016},
issn = {1090-2120},
abstract = {Alzheimer's disease (AD) is a debilitating neurodegenerative disorder for which effective therapies remain an urgent unmet need. This study investigated the therapeutic potential of the synthetic nucleoside analogue ribavirin in transgenic Caenorhabditis elegans (C. elegans) models of AD. We demonstrate that ribavirin specifically reduced the paralysis rate and improved short-term non-associative learning capacity of the Aβ AD models. These functional benefits were supported by a marked reduction in Aβ aggregation in vivo and a direct inhibition of Aβ structural transition from α-helix to β-sheet in vitro. Moreover, ribavirin could stably bind to the Aβ1-42 pentamer, disrupt the existing β-sheet networks, and increase the solvent exposure of hydrophobic residues. Mechanistically, ribavirin exerted its neuroprotective effects by enhancing lysosomal activity, attenuating Aβ-induced activation of the integrated stress response (ISR) in C. elegans models. Genetic studies further revealed that the efficacy of ribavirin was functionally dependent upon AMPK signalling, suggesting critical role of AMPK pathway. Crucially, ribavirin acted selectively, as it did not broadly activate other canonical stress responses. These findings establish a strong mechanistic rationale for repurposing ribavirin as a potential neuroprotective agent targeting AD.},
}

@article {pmid42379091,
year = {2026},
author = {Athira, ET and Satija, J},
title = {Exploring peroxidase substrates driven etching of gold nanorods towards indirect detection of amyloid beta1-42.},
journal = {Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy},
volume = {363},
number = {Pt 2},
pages = {128318},
doi = {10.1016/j.saa.2026.128318},
pmid = {42379091},
issn = {1873-3557},
abstract = {Plasmonic enzyme-linked immunosorbent assay (pELISA) leverages the localized surface plasmon resonance (LSPR) property of noble metal nanoparticles to achieve enhanced sensitivity compared to conventional immunoassays. The geometric alteration of plasmonic nanoparticles through oxidative moieties generates distinct colorimetric signals that can be employed to develop an ultrasensitive point-of-care pELISA. Advancing pELISA requires a systematic exploration of enzymatic reactions and nanomaterials, allowing for the precise detection of trace biomolecules. The study systematically investigates the etching efficiency of gold nanorods (AuNRs) using the products of five horseradish peroxidase (HRP) substrates, i.e., 3,3,5,5-tetramethylbenzidine (TMB), o-phenylene diamine dihydrochloride (OPD), 2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS), 3-amino-9-ethylcarbazol (AEC), and 3,3'diaminobenzidine (DAB). Each substrate was evaluated under controlled conditions to determine its ability to induce aspect ratio-dependent spectral shifts in AuNRs, enabling quantitative colorimetric detection. UV-Vis spectroscopy reveals that only the oxidized product of TMB (TMBox2) significantly etches the AuNRs, producing a notable blue shift in the LSPR peak. The optimized etching approach was applied to develop an indirect competitive pELISA for detecting amyloid beta1-42 (Aβ1-42), a key biomarker for Alzheimer's disease. This method demonstrated a limit of detection of 0.37 pg/mL (≈83.14 fM), highlighting its potential for ultrasensitive and precise biomolecule quantification.},
}

@article {pmid42379112,
year = {2026},
author = {Surer, HK and Yaylagul, NK},
title = {Effectiveness of a structured caregiver support program for caregivers of people with Alzheimer's disease: A mixed methods study.},
journal = {Geriatric nursing (New York, N.Y.)},
volume = {72},
number = {},
pages = {104170},
doi = {10.1016/j.gerinurse.2026.104170},
pmid = {42379112},
issn = {1528-3984},
abstract = {The aim of this study was to evaluate the effect of the Structured Caregiver Support Program (SCSP) on caregiver burden, psychological well-being and psychological resilience of informal caregivers of people with Alzheimer's disease. A mixed-method research design, comprising both quantitative and qualitative research methods was used in this study. The quantitative part of the study was designed as a randomized controlled study with a pretest-posttest design. In the qualitative part of the study, a phenomenological approach was used and three focus group interviews were conducted. The quantitative findings of the study show that the SCSP produced a statistically significant difference in the intervention group compared to the control group in terms of reducing caregiver burden and improving psychological well-being and psychological resilience levels (p < 0.05). The effect sizes (Cohen's d) obtained from the post-test comparisons between groups ranged from 0.921 to 2.134, indicating a "large" effect size. In the qualitative findings of the study as a result of thematic analysis, three main themes emerged: "need for an intervention program", "changes brought about by the intervention program", and "evaluation of the intervention program". The SCSP is easy to implement and cost-effective. It can be used as a practical intervention program, especially for professionals working in health and care services.},
}

@article {pmid42379387,
year = {2026},
author = {Larrán, B and López-Alonso, M and Miranda, M and González-Martínez, Á and Rosado, B and García-Belenguer, S and Herrero-Latorre, C and Insua, D and Suárez, ML and Santamarina, G and Orjales, I},
title = {Brain mineral concentrations in canine cognitive dysfunction.},
journal = {Veterinary journal (London, England : 1997)},
volume = {},
number = {},
pages = {106766},
doi = {10.1016/j.tvjl.2026.106766},
pmid = {42379387},
issn = {1532-2971},
abstract = {Canine cognitive dysfunction (CCD) is a prevalent age-related neurodegenerative condition in dogs that shares several features with Alzheimer's disease (AD). Although mineral dyshomeostasis has been implicated in the pathogenesis of AD, its role in CCD remains largely unexplored. This retrospective study aimed to investigate regional brain mineral concentrations in 24 dogs with CCD and 15 dogs exhibiting successful cognitive aging (non-CCD). CCD diagnosis was based on the results of caregiver questionnaires, physical examination and laboratory analyses after ruling out any other intracranial disease. Four cortical regions with high β-amyloid pathology (prefrontal, parietal, temporal and occipital cortex) and one generally unaffected region (cerebellum) were analysed to determine the concentrations of 20 minerals by using plasma-based optical techniques and mass spectrometry. Compared to non-CCD dogs, CCD dogs had significantly lower concentrations of Ca, Fe, Mg, Mn and Zn, and higher levels of Cd, Mo, Ni and Pb in specific brain regions. The greatest number of significant differences were observed in the prefrontal cortex, the earliest and most consistently affected region in CCD, whereas the cerebellum remained largely unchanged. Principal component analysis distinguished CCD from non-CCD dogs and, within the CCD group, showed clustering of the cerebellum separately from cortical regions. The regional specificity of these alterations and their ability to distinguish CCD from non-CCD dogs support a link between disrupted mineral homeostasis and CCD. Notably, lower concentrations affected essential trace elements involved in antioxidant defence, neuronal signalling and neurotransmission, raising the possibility of functional implications that warrants further investigation.},
}

@article {pmid42379406,
year = {2026},
author = {Sp, D and Lee, M and Kim, J and Cho, YJ and Kim, SH and Yang, HJ},
title = {Neuro-Ocular Amyloid Characterization in Alzheimer's Disease via Cross-Site PET-MRI and Hierarchical Cross-Attention Driven Multimodal Representation Learning.},
journal = {NeuroImage},
volume = {},
number = {},
pages = {122081},
doi = {10.1016/j.neuroimage.2026.122081},
pmid = {42379406},
issn = {1095-9572},
abstract = {The eye is often described as a window to the brain and may offer a non-invasive opportunity for investigating neurodegenerative changes. Although cerebral amyloid-β (Aβ) accumulation is a well-established hallmark of Alzheimer's disease (AD), the potential of ocular regions to capture aspects of this pathology in positron emission tomography (PET) remains underexplored. Our primary objective is to conduct a radiomics-SUVR analysis to investigate the relationship between ocular regions of interest (ROI) extracted from PET imaging and regional SUVR values obtained from six brain PET regions. Our secondary objective is to address domain shifts arising from heterogeneous data distributions across imaging sites during ocular segmentation. This study included 228 participants from Chonnam National University Hospital (CNUH) and an external validation cohort of 50 participants from ADNI-4, all with paired [18]F-florbetaben PET and 3D T2-weighted MRI. For the segmentation task, we propose HCA-Net, a Hierarchical Cross-Attention Network that integrates co-registered PET and MRI using a multi-scale fusion strategy, allowing the model to better handle domain shifts in cross-site imaging conditions. For the radiomics-SUVR analysis, the segmented ocular ROI was classified into Aβ[+] and Aβ[-] groups using a CNN model. Radiomic features were then extracted and compared with corresponding regional brain SUVRs using statistical methods. While several features showed group differences at an uncorrected threshold, only one feature remained significant after correction for multiple comparisons highlighting the need for further validation. Correlation analyses identified modest associations between ocular radiomics and regional brain SUVRs, highlighting the influence of global amyloid burden on these relationships. Overall, our study presents a multimodal cross-site segmentation framework and provides preliminary evidence of neuro-ocular associations in AD through [18]F-FBB PET imaging, highlighting the need for further validation.},
}

@article {pmid42379471,
year = {2026},
author = {Yi, C and Chen, W and Shi, X and Lin, Y and Zheng, Y and Luo, G and Pei, Z and Zhang, X},
title = {DTI-ALPS Associations with Regional Amyloid Deposition and Glucose Metabolism in Mild Cognitive Impairment and Alzheimer's Disease.},
journal = {Journal of neuroradiology = Journal de neuroradiologie},
volume = {},
number = {},
pages = {101586},
doi = {10.1016/j.neurad.2026.101586},
pmid = {42379471},
issn = {0150-9861},
abstract = {OBJECTIVES: The DTI analysis along the perivascular space (DTI-ALPS) index is widely used to assess water diffusion alterations in Alzheimer's disease (AD), yet its biological interpretation remains debated. We investigated DTI-ALPS associations with regional amyloid-β (Aβ) deposition, glucose metabolism, and cognitive function in Chinese patients with AD and mild cognitive impairment (MCI), offering finer-grained imaging evidence for its pathophysiological interpretation.

METHODS: 34 AD dementia (ADD) patients, 40 MCI patients, and 52 cognitively normal controls (NCs) underwent MRI, [18]F-florbetapir ([18]F-AV45) (standardized uptake value ratio, SUVR; centiloid values, CL), and [18]F-FDG (SUVR) imaging. MRI volumetry and PET quantification used Neurophet SCALE PET software. Mediation analysis tested ALPS effects between pathology/metabolism and cognition.

RESULTS: ALPS differed significantly across groups (ADD:1.152±0.113; MCI:1.247±0.122; NC:1.302±0.121; p<0.001). Adjusted for age, sex, education, and APOE4, ALPS correlated positively with MMSE (r=0.324, p<0.001) and MoCA (r=0.311, p<0.001) and negatively with CL (r=-0.415, p<0.001). The ALPS index showed negative correlations with [18]F-AV45 PET SUVR in nearly all brain regions, with the strongest negative associations observed in the posterior cingulate (r=-0.459), paracentral (r=-0.445), superior frontal (r=-0.441), and inferior temporal (r=-0.433) regions. For [18]F-FDG PET SUVR, the ALPS index demonstrated bidirectional correlations: positive in regions including the inferior parietal (r=0.396), isthmus of cingulate (r=0.376), and precuneus (r=0.369), but negative in the paracentral (r=-0.418), precentral (r=-0.406), and cerebellar white matter (r=-0.374) (all p<0.001). Mediation analysis revealed that the ALPS index mediates the relationships between glucose metabolism/Aβ accumulation and both abstract thinking and memory. Parietal/cingulate isthmus/precuneus FDG metabolism showed significant ALPS-mediated indirect effects across cognitive domains (p<0.05).

CONCLUSIONS: The ALPS index correlates with Aβ deposition and exhibits region-specific metabolic associations in AD, mediating amyloid-metabolism-cognition pathways and predicting cognitive decline. These findings provide a region-wise correlation map of perivascular water diffusion alterations in AD, informing future research directions, though underlying mechanisms require validation.},
}

@article {pmid42379954,
year = {2026},
author = {Broatch, JR and Saner, NJ and Jackson, ML and Syeda, W and Bishop, DJ and Brodtmann, A},
title = {Exercise as a regulator of glymphatic function.},
journal = {Trends in neurosciences},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.tins.2026.06.002},
pmid = {42379954},
issn = {1878-108X},
abstract = {The glymphatic system is a brain-wide perivascular network hypothesized to facilitate the clearance of waste products that accumulate during normal brain activity, including neurotoxic proteins implicated in neurodegenerative diseases. Emerging evidence suggests that exercise may modulate glymphatic function, offering a potential mechanism to help explain the neuroprotective effects of exercise. In this review, we synthesize evidence from animal models and humans on the organization and regulation of the glymphatic system, examine its vulnerability to aging and neurodegenerative pathology, and discuss the potential roles of exercise in enhancing its function. We propose that the convergence between known regulators of glymphatic function and the physiological adaptations to exercise provides a mechanistic framework linking physical activity to glymphatic integrity and brain resilience.},
}

@article {pmid42380051,
year = {2026},
author = {Maia, M and Monteiro, AR and Martins, MS and Martinez-Gonzalez, L and Martínez, A and Remião, F and Silva, R and Sousa, E},
title = {Novel Xanthene Derivatives for Neuroprotection in Alzheimer's Disease-Synthesis and Biological Assessment.},
journal = {ChemMedChem},
volume = {21},
number = {13},
pages = {e70352},
doi = {10.1002/cmdc.70352},
pmid = {42380051},
issn = {1860-7187},
support = {UIDB/04423/2020//Fundação para a Ciência e a Tecnologia/ ; UIDP/04423/2020//Fundação para a Ciência e a Tecnologia/ ; SFRH/BD/146211/2019//Fundação para a Ciência e a Tecnologia/ ; 10.54499/2021.05964.B//Fundação para a Ciência e a Tecnologia/ ; UIDP/04378/2020//Fundação para a Ciência e a Tecnologia/ ; UIDB/04378/2020//Fundação para a Ciência e a Tecnologia/ ; },
mesh = {Humans ; *Alzheimer Disease/drug therapy/metabolism/pathology ; *Neuroprotective Agents/pharmacology/chemical synthesis/chemistry ; *Xanthenes/pharmacology/chemistry/chemical synthesis ; Amyloid beta-Peptides/metabolism/antagonists & inhibitors ; Structure-Activity Relationship ; Cell Line, Tumor ; Cell Survival/drug effects ; ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism ; Molecular Structure ; Dose-Response Relationship, Drug ; Peptide Fragments ; },
abstract = {Alzheimer's disease (AD) is recognized by the World Health Organization as a global public health priority. There is an urgent need to develop disease-modifying therapies or treatments (DMT's) to prevent, delay, or slow the progression and target the primary AD pathophysiology mechanisms. Following previous works on the activity of tricyclic compounds in neuroprotection, this work focuses on the synthesis of novel xanthene derivatives. Eighteen compounds were obtained and assessed regarding their cytotoxicity, central nervous system (CNS) penetration, P-glycoprotein (P-gp) modulation, and neuroprotective effects against iron- and amyloid-beta (Aβ)-induced cytotoxicity. Generally, the derivatives were well tolerated by differentiated human neuroblastoma SH-SY5Y cells at concentrations up to 25 μM. Regarding their ability to activate P-gp, compounds 5, 7, 9, 11, 12, and 16 showed the most significant increases in P-gp activity. Neuroprotection assays demonstrated the ability of several xanthene derivatives to counteract iron (III)- and Aβ-induced cytotoxicity. It was clearly demonstrated the P-gp involvement in compound-mediated ability to reverse the cytotoxicity induced by the Aβ25-35 peptide. Additionally, parallel artificial membrane permeability assay (PAMPA) studies showed their potential to penetrate the blood-brain barrier (BBB) and reach the CNS, which is a crucial requirement for their potential biological activity in AD.},
}

Humans
*Alzheimer Disease/drug therapy/metabolism/pathology
*Neuroprotective Agents/pharmacology/chemical synthesis/chemistry
*Xanthenes/pharmacology/chemistry/chemical synthesis
Amyloid beta-Peptides/metabolism/antagonists & inhibitors
Structure-Activity Relationship
Cell Line, Tumor
Cell Survival/drug effects
ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism
Molecular Structure
Dose-Response Relationship, Drug
Peptide Fragments

@article {pmid42380069,
year = {2026},
author = {Zhang, Y and Qiao, H and Lv, Z and Guo, R and Li, D and Song, W and Wang, D},
title = {Transcranial 810 nm Pulsed Photobiomodulation Improves Learning and Reduces Aβ42 Burden in APP/PS1 Mouse Model of Alzheimer's Disease.},
journal = {Photobiomodulation, photomedicine, and laser surgery},
volume = {},
number = {},
pages = {25785478261465371},
doi = {10.1177/25785478261465371},
pmid = {42380069},
issn = {2578-5478},
abstract = {BACKGROUND: Alzheimer's disease (AD) is a leading cause of dementia in older adults, and effective and widely applicable treatment options remain limited. Photobiomodulation (PBM) has shown promise for AD. However, reported estimates of the delivered dose after transcranial propagation vary widely, limiting translation from animal models to clinical settings.

OBJECTIVE: Building on our team's prior clinical findings, this study evaluated whether an 810 nm/10 Hz pulsed PBM regimen improves cognitive performance and reduces Aβ42 burden in APP/PS1 mice.

METHODS: APP/PS1 mice received PBM using an 810 nm LED pulsed at 10 Hz. Irradiation was delivered for 540 sec/day, 6 days/week, for 7 weeks, with a scalp-surface power density of 0.025 W/cm[2] and an energy density of 13.5 J/cm[2]. Cognitive function was evaluated using the Morris water maze, and Aβ42 burden was quantified by immunofluorescence.

RESULTS: Cortical and hippocampal Aβ42 plaque burden was reduced, p < 0.01. Exploratory correlation analyses suggested an association between hippocampal Aβ42 plaque number and reversal-learning performance in the histological subset, p = 0.02. The microglia-Aβ42 colocalization ratio increased by 7.53%, p = 0.03, indicating enhanced spatial association between microglia and Aβ42 after PBM.

CONCLUSIONS: These findings support further evaluation of this 810 nm/10 Hz pulsed PBM regimen in AD mouse models and highlight the value of standardized PBM parameter reporting in preclinical studies.},
}

@article {pmid42380191,
year = {2026},
author = {de Rojas, I and García-González, P and Olivé, C and Puerta, R and Montrreal, L and Alegret, M and Sotolongo-Grau, O and Cano, A and Marquié, M and Valero, S and Calero, M and Rábano, A and Pastor, AB and Del Ser, T and Quintela, I and Macías, J and Corma-Gómez, A and Pineda, JA and Franco-Macías, E and Buiza-Rueda, D and Bernal Sánchez-Arjona, M and Royo, JL and Mendoza, S and Lage, C and Antúnez, C and Corbatón-Anchuelo, A and Martínez-Larrad, MT and Diez-Fairen, M and Alvarez, I and Huerto Vilas, R and Arias Pastor, A and Menéndez-González, M and Martínez Rodríguez, C and Rosas Allende, I and García-Madrona, S and Frank-García, A and Martín-Montes, A and Baquero, M and , and , and Pérez-Tur, J and Bullido, MJ and Garcia-Ribas, G and Álvarez, V and Piñol-Ripoll, G and Pastor, P and Rodriguez-Rodriguez, E and García-Alberca, JM and Mir, P and Real, LM and Medina, M and Sáez, ME and Carracedo, Á and Heneka, MT and Tàrraga, L and Boada, M and Sánchez-Juan, P and Fernández, MV and van der Lee, SJ and Ruiz, A},
title = {Landscape of copy number variants in Spanish people with dementia.},
journal = {NPJ genomic medicine},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41525-026-00589-6},
pmid = {42380191},
issn = {2056-7944},
support = {FI20/00215//Instituto de Salud Carlos III/ ; CD22/00125//Instituto de Salud Carlos III/ ; PI17/01474, PI19/00335, PI22/01403 and PI22/00258//Instituto de Salud Carlos III/ ; CNV-304-PRF-866//Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas/ ; CB06/05/2004 and CB18/05/00010//Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas/ ; GR@ACE project//'la Caixa' Foundation/ ; GR@ACE project//Fundación ADEY/ ; GR@ACE project//Fundación Echevarne/ ; GR@ACE project//Grifols/ ; PID2021-122473OA-I00, PID2021-123462OB-I00 and PID2019-106625RB-I00//Spanish Ministry of Science and Innovation, Proyectos de Generación de Conocimiento/ ; PMP22/00022//NextGenerationEU/ ; Nº PR067/21//Agency for Innovation and Entrepreneurship (VLAIO)/ ; Nº 115975//EU/EFPIA Innovative Medicines Initiative Joint/ ; ADAPTED and HARPONE projects//Janssen Pharmaceutica/ ; Nº AC19/00097//Joint Program for Neurodegenerative Diseases (JPND)/ ; DESCARTES project//German Research Foundation (DFG)/ ; STAR Award//University of Texas System/ ; },
abstract = {Recent studies suggest that copy number variants (CNVs) may contribute to the missing heritability of complex diseases such as Alzheimer's disease (AD) and related dementias (ADRD). We performed a CNV analysis using genotyping data (Axiom 815 K Spanish biobank array) from the GR@ACE/DEGESCO dementia dataset (n = 20,067) of the Spanish population. Applying PennCNV and extensive quality control, 8275 controls and 7818 dementia cases were selected for gene-level case/control associations. We identified 43,833 CNVs with deletions (47%) and duplications (53%). No genome-wide significant associations were found, but nominal associations were observed in PKP3-SIGIRR and FBRSL1 loci. CNVs in 2970 genes were exclusive to dementia cases and enriched in vascular-related pathways. Notable findings included 14q11.2 duplication and VPS13B deletions in ADRD cases, the latter confirmed by optical genome mapping. Our findings suggest potential novel genes associated with ADRD in the Spanish population. However, the limited resolution of array-based technologies in detecting CNVs warrants further investigation.},
}

@article {pmid42380200,
year = {2026},
author = {Kazmi, SA and Chandra, F and Wasney, M and Cheng, J and Lum, GR and Iyer, M and Di Blasi, D and Espinoza, AN and Lopez-Romero, A and Yang, X and Garud, N and Hsiao, EY},
title = {Select microbial metabolites promote tau aggregation in a murine tauopathy model.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-74775-6},
pmid = {42380200},
issn = {2041-1723},
support = {2018-191860//Silicon Valley Community Foundation (SVCF)/ ; },
abstract = {The gut microbiome is emerging as a modifier of risk for neurodegenerative diseases, but underlying mechanisms remain poorly understood. Here, we show that the hTau.P301S mouse model for progressive tauopathy develops alterations in the composition and function of the gut microbiome that are not recapitulated in amyloid-based 5xFAD or 3xTg models for Alzheimer's disease. Disrupting the gut microbiome via chronic antibiotic treatment exacerbates cognitive deficits and tau pathology in hTau.P301S mice, demonstrating a causal influence of the microbiome on tau-driven disease progression. This corresponds with widespread alterations in microbiome-dependent metabolites in the sera and brains of hTau.P301S mice, including subsets that correlate with the severity of tau pathology. By screening against tau biosensor cells, we identify select microbial metabolites-trimethylamine-N-oxide, 3-indoxyl sulfate, phenol sulfate, thymidine, and 2'deoxyuridine-that promote tau seeding and aggregation. Systemic administration of these metabolites worsens cognitive impairment and tau pathology in hTau.P301S mice. These findings establish a mechanistic link between the gut microbiome, serum and brain metabolites, as well as tau aggregation, suggesting that select microbial metabolites could potentially serve as therapeutic targets for tau-driven diseases.},
}

@article {pmid42380532,
year = {2026},
author = {Mazahir, I and Wali, B and Rehman, AS and Deep, G and Mangla, A and Jindal, G and Khan, H and Parvez, S and Raisuddin, S},
title = {Alpha Lipoic Acid Mitigates TBI-Induced Neuroinflammation by Regulating S100B/STIM Signaling via NF-ƙB Pathway.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {42380532},
issn = {1559-1182},
mesh = {Animals ; Male ; *Brain Injuries, Traumatic/metabolism/complications/pathology/drug therapy ; Rats, Wistar ; *Signal Transduction/drug effects ; *Thioctic Acid/pharmacology/therapeutic use ; *S100 Calcium Binding Protein beta Subunit/metabolism ; *NF-kappa B/metabolism ; *Neuroinflammatory Diseases/drug therapy/metabolism/pathology/etiology ; Microglia/metabolism/drug effects/ultrastructure ; Neuroprotective Agents/pharmacology ; Maze Learning/drug effects ; },
abstract = {Alpha-lipoic acid (ALA) is a natural compound present in plants, animals, and humans. It provides neuroprotection through its antioxidant action, reducing oxidative stress and inflammation via pathways such as the Nrf-2 signalling pathway. It has shown protective effect against neuronal damage in Alzheimer's disease and Parkinson's disease. The traumatic brain injury (TBI) is a major cause of cognitive and motor impairments. TBI primarily initiates a series of secondary injury pathways, with glutamate excitotoxicity being a critical factor in neuronal degeneration. In this study, we investigated the protective effects of ALA on TBI induced by controlled cortical impact (CCI) in the cerebral cortex (CC) and hippocampus (HC) regions of the Wistar rats. TBI parameters were analysed using behavioural assays, including the Barnes maze test (BMT), beam balance test, grip strength, and Y-maze test (YMT). In addition, we measured brain water content, and analyzed histological alterations by light microscopy, microglial changes by the immunofluorescence technique, and ultrastructural changes by the transmission electron microscopy (TEM). Expression of markers of glutaminergic and calcium (Ca[2][+]) pathways was analysed by qRT-PCR and western blotting. ALA was administered following TBI induction in rats. It was shown that ALA downregulated S100B and the N-methyl-D-aspartate (NMDA) receptor subunit 2B (GRIN2B) mRNA expression. However, TBI-dependent alterations in excitatory amino acid transporter (EAAT) expression were downregulated in the CC region of adult rats with TBI. Protein expression of S100B, stromal interaction molecule (STIM), ubiquitin C-terminal hydrolase L1 (UCHL1), nuclear factor kappa (NF-ƙB), and glial fibrillary acidic protein (GFAP) was increased in the TBI group, as analysed by immunoblotting. Furthermore, expression of Iba1[+], a marker of microglial activation, was increased in TBI and mitigated by ALA. Overall, this study helps us understand the role of ALA as a mitigating compound in the TBI-induced rat model.},
}

Animals
Male
*Brain Injuries, Traumatic/metabolism/complications/pathology/drug therapy
Rats, Wistar
*Signal Transduction/drug effects
*Thioctic Acid/pharmacology/therapeutic use
*S100 Calcium Binding Protein beta Subunit/metabolism
*NF-kappa B/metabolism
*Neuroinflammatory Diseases/drug therapy/metabolism/pathology/etiology
Microglia/metabolism/drug effects/ultrastructure
Neuroprotective Agents/pharmacology
Maze Learning/drug effects

@article {pmid42380654,
year = {2026},
author = {Saha, P and Chouhan, A},
title = {QUAD: a composite risk framework integrating uncertainty, applicability domain, and model disagreement for reliable QSAR predictions.},
journal = {Journal of computer-aided molecular design},
volume = {40},
number = {1},
pages = {},
pmid = {42380654},
issn = {1573-4951},
mesh = {*Quantitative Structure-Activity Relationship ; *Amyloid Precursor Protein Secretases/antagonists & inhibitors/chemistry/metabolism ; *Aspartic Acid Endopeptidases/antagonists & inhibitors/chemistry/metabolism ; *Glycogen Synthase Kinase 3 beta/antagonists & inhibitors/chemistry/metabolism ; Uncertainty ; Humans ; *Alzheimer Disease/drug therapy ; Reproducibility of Results ; Random Forest ; Models, Molecular ; },
abstract = {Reliable prediction confidence estimation remains a major challenge in quantitative structure-activity relationship (QSAR) modeling, particularly when models are applied to structurally novel compounds or heterogeneous experimental datasets. Although several uncertainty quantification approaches have been proposed, the relative behavior of complementary reliability indicators under extrapolative validation conditions remains insufficiently characterized. In the present study, we introduce QUAD, a post-hoc reliability estimation framework integrating ensemble-based uncertainty, model disagreement, and applicability-domain (AD) risk into a unified molecule-level reliability score. The framework was evaluated using Random Forest regression and ECFP4 molecular fingerprints on two Alzheimer's disease-related benchmark datasets targeting β-site amyloid precursor protein cleaving enzyme 1 (BACE1) and glycogen synthase kinase-3β (GSK3β). Reliability behavior was systematically assessed under both conventional random train-test validation and more stringent Bemis-Murcko scaffold-based validation. In addition to evaluating the integrated QUAD framework, component-wise ablation analysis and reliability enrichment analysis were performed to investigate the relative contributions of uncertainty, disagreement, and applicability-domain information. Under conventional random-split evaluation, ensemble uncertainty demonstrated the strongest and most consistent correlation with prediction error across both datasets. For BACE1, uncertainty achieved Pearson and Spearman correlations of 0.366 and 0.338, respectively, while the integrated QUAD framework produced lower correlations (Pearson r = 0.303, Spearman ρ = 0.244). In contrast, GSK3β exhibited stronger overall reliability behavior, with QUAD retaining substantial correlation with prediction error (Pearson r = 0.439). Scaffold-based evaluation revealed pronounced dataset-dependent differences. Under scaffold extrapolation, QUAD performance deteriorated substantially in BACE1 (Pearson r = 0.071), whereas GSK3β retained comparatively robust reliability behavior (Pearson r = 0.363). Ablation analyses further demonstrated that ensemble uncertainty represented the most stable reliability indicator across validation regimes, while disagreement-based reliability estimation exhibited substantial sensitivity to structural extrapolation. Taken together, the present results indicate that integrated reliability estimation frameworks should not be interpreted as universally superior to individual uncertainty estimation approaches. Instead, the effectiveness of composite reliability estimation appears strongly dependent on dataset-specific relationships between constituent reliability indicators and validation conditions. The study further highlights the importance of scaffold-based evaluation for realistic assessment of molecule-level reliability estimation strategies in practical QSAR deployment scenarios.},
}

*Quantitative Structure-Activity Relationship
*Amyloid Precursor Protein Secretases/antagonists & inhibitors/chemistry/metabolism
*Aspartic Acid Endopeptidases/antagonists & inhibitors/chemistry/metabolism
*Glycogen Synthase Kinase 3 beta/antagonists & inhibitors/chemistry/metabolism
Uncertainty
Humans
*Alzheimer Disease/drug therapy
Reproducibility of Results
Random Forest
Models, Molecular

@article {pmid42380894,
year = {2026},
author = {Almeida-Meza, P and Dregan, A and Croak, B and Hettiaratchy, S and Fear, NT and Stevelink, SAM},
title = {Leveraging primary care data to understand military veteran health in England: feasibility study and matched-control comparison of recorded conditions.},
journal = {BMC medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12916-026-05005-5},
pmid = {42380894},
issn = {1741-7015},
support = {FiMT21/1023KCL//Forces in Mind Trust/ ; },
abstract = {BACKGROUND: Evidence on the health needs of UK veterans accessing primary care is limited. Electronic health records (EHRs) offer an opportunity to address this evidence gap if veterans are correctly identified. This study validated the identification of veterans in the Clinical Practice Research Datalink (CPRD) and assessed its feasibility for examining their health compared with non-veterans.

METHODS: We conducted a matched cohort study in CPRD, the largest primary care database in the UK, identifying veterans using military-related codes in patients' EHRs. Each veteran was matched to one or two non-veterans on age, gender, practice, and index date. Validation was undertaken through general practitioner confirmation of veteran status. We compared demographics, risk factors and recorded health conditions using descriptive statistics. Poisson regressions assessed the association between veteran status and various physical and mental health conditions.

RESULTS: 122,484 veterans and 244,573 matched non-veterans were identified. 95% were captured using definite military terms, and validation showed substantial agreement with GP records. Veterans had higher recorded prevalence across all conditions. The largest differences were observed for PTSD (adjusted prevalence ratio [aPR] 16.43, 95% CI 14.89-18.13), followed by Alzheimer's disease (aPR 2.74, 95% CI 2.56-2.92), alcohol use disorder (aPR 2.23, 95% CI 2.09-2.39), hearing loss (aPR 2.09, 95% CI 2.02-2.15), and osteoarthritis (aPR 1.98, 95% CI 1.93-2.03). Recorded prevalence was also higher among veterans for COPD (aPR 1.83, 95% CI 1.77-1.89), depression (aPR 1.83, 95% CI 1.79-1.87), prostate cancer (aPR 1.83, 95% CI 1.73-1.94), coronary heart disease (aPR 1.78, 95% CI 1.72-1.84), lower back pain (aPR 1.73, 95% CI 1.70-1.77), and myocardial infarction (aPR 1.65, 95% CI 1.56-1.75). Differences for anxiety and breast cancer were modest.

CONCLUSIONS: This study establishes a foundation for UK veterans' health research using primary care data. Provided that identification and recording of veteran status improve in NHS records, CPRD offers considerable potential to monitor veteran health trends, identify needs, and evaluate interventions at scale.},
}

@article {pmid42381088,
year = {2026},
author = {Verberk, IMW and de Koning, LA and Coomans, EM and Trieu, C and Leeuwis, AE and Hunter, J and Honigberg, L and van der Flier, WM and Vijverberg, EGB and Ossenkoppele, R and van de Giessen, E and Teunissen, CE},
title = {The potential of key Alzheimer's plasma biomarkers to mimic tau PET MUBADA-based disease staging.},
journal = {Alzheimer's research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13195-026-02085-6},
pmid = {42381088},
issn = {1758-9193},
abstract = {BACKGROUND: Patients with Alzheimer's disease (AD) with a low to intermediate tau-PET burden might benefit most from anti-amyloid treatment. Staging tau burden with plasma biomarkers would offer a scalable alternative to staging with tau-PET. This study investigated whether key plasma biomarkers P-tau217, P-tau181, Aβ42/40, GFAP and NfL can be used to accurately stage amyloid status (A-/A+) and tau-PET burden, and evaluated the relation of such a plasma-based staging system with cognitive outcomes over time.

METHODS: We included 105 participants with subjective cognitive decline (n = 27 A-, n = 18 A+), A+ mild cognitive impairment (n = 10) or A + AD-dementia (n = 50) from the Amsterdam Dementia Cohort who underwent [[18]F]flortaucipir PET-burden assessment (Tlow, Tintermediate or Thigh; based on MUBADA SUVr) and longitudinal cognitive assessment (average follow-up: 4.1 ± 3.5 years). AD-related plasma biomarkers were measured with Simoa. Discriminative performance (AUC) of each marker was compared using ROC analysis, and combined utility was assessed with logistic regression. Subsequently, cutoffs were established aiming for 90%-specificity, to regroup participants into a plasma-based staging scheme. Age-, sex- and education-adjusted linear mixed models (LMM) were performed to compare associations of plasma versus PET-based staging with longitudinal cognition.

RESULTS: 27 participants were A-TPET_low, 22 A+TPET_low, 27 A+TPET_int and 29 A+TPET_high. To discriminate A-TPET_low participants from A+TPET_low/int participants, P-tau217 performed best among all measured markers P-tau217, P-tau181, Aβ42/40, GFAP and NfL (AUC = 0.92 [95% CI: 0.856-0.985]). To discriminate A+TPET_high participants from A+TPET_low/int participants, also P-tau217 performed best among all markers (AUC = 0.74 [95% CI: 0.618-0.862]). A combination of Wald's backward-selected plasma markers did not statistically improve discriminative performance (DeLong's p > 0.05; two-marker combinations selected). Applying two cutoffs for P-tau217 as well as for the two-marker combinations, at 90% specificity to discriminate subsequent groups, we derived two plasma-based staging schemes. While the tau-PET staging scheme significantly and consistently associated with cognitive performance and decline across cognitive domains in LMMs, the plasma staging schemes did not.

CONCLUSIONS: Performance of plasma-based staging approaches developed in this study were high when discriminating individuals without amyloid pathology, while this was moderate when discriminating amyloid positive individuals with a high tau-PET burden. Our LMM findings visualize that tau staging in amyloid-positive individuals remains optimally performed with tau-PET scans.},
}

@article {pmid42381106,
year = {2026},
author = {Seok, JW and Kim, K and Kim, JU and Chun, JM},
title = {Association of inflammatory fluid biomarkers with the progression of Alzheimer's disease: a protocol for a systematic review and meta-analysis.},
journal = {Systematic reviews},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13643-026-03252-4},
pmid = {42381106},
issn = {2046-4053},
support = {NSN2512053//Ministry of Science and ICT, South Korea/ ; },
abstract = {BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disease that typically begins with mild cognitive impairment (MCI) and gradually worsens to mild, moderate, and severe dementia. There is increasing evidence that inflammatory responses in both peripheral and central compartments contribute to the pathophysiology of AD. However, meta-analyses that compare the changes in inflammatory biomarkers according to AD stages remain limited. This study aims to systematically evaluate the differences in inflammatory marker levels according to AD progression stages and to assess their potential utility as stage-specific biological indicators.

METHODS: This meta-analysis will be conducted according to the PRISMA-P guidelines. PubMed, Embase, Cochrane Library, and MEDLINE will be searched for studies involving elderly people aged 60 years or older with MCI or AD diagnosed through June 30, 2025. According to the PECO framework, the primary comparison will be each AD-related clinical stage, including MCI, mild AD, moderate AD, and severe AD, versus cognitively normal older adults. Secondary analyses will examine between-stage comparisons when sufficient data are available. The primary outcomes will be inflammatory biomarker levels measured in blood-derived samples, including serum and plasma. Cerebrospinal fluid inflammatory biomarkers will be included as predefined secondary outcomes and analyzed separately. Biomarkers of interest include IL-6, CRP, TNF-α, IL-1β, YKL-40, complement C3, C5a, IL-2, IFN-γ, GFAP, sTREM2, ferritin, and related inflammatory markers. Literature selection and data extraction will be performed independently by two reviewers. Statistical analysis will be performed using JASP to calculate the standardized mean differences (SMD) and 95% CI. A heterogeneity test, meta-regression, subgroup analysis, sensitivity analysis, and publication bias test will also be performed.

DISCUSSION: This study will systematically evaluate stage-specific changes in inflammatory biomarkers and identify potential response patterns and biological relevance of each marker in relation to AD progression. This review will examine whether some biomarkers follow nonlinear trajectories rather than linear changes, which may help explore their association with pathological mechanisms such as microglial activation and peripheral-central immune axis changes. This meta-analysis may provide foundational data for the development of inflammatory fluid biomarkers for early diagnosis and stage-specific prognosis in AD.

As this protocol is not eligible for registration in PROSPERO, a preliminary search has been performed to confirm that there are no duplicate systematic reviews.},
}

@article {pmid42381140,
year = {2026},
author = {Li, Y and Xie, K and Qian, S and Wang, Z and Zhang, H and Si, L},
title = {Quantifying Short-Term Functional Changes After Lecanemab Treatment in Early Alzheimer's Disease: An Exploratory 3-Month Follow-Up Case Report Using Eye Movement and Gait Analysis.},
journal = {Current Alzheimer research},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115672050471024260520113701},
pmid = {42381140},
issn = {1875-5828},
abstract = {INTRODUCTION: Lecanemab is a monoclonal antibody targeting amyloid-β (Aβ) and is currently used in clinical practice for the treatment of early Alzheimer's disease (AD). However, noninvasive biomarkers reflecting its early efficacy are still unclear. This exploratory case report aims to investigate the combination of eye movement and gait analysis to quantitatively monitor shortterm functional changes during lecanemab treatment.

CASE PRESENTATION: Two male patients, both diagnosed with mild Alzheimer's disease through amyloid- PET and both with the APOE ε3/ε3 genotype, received intravenous lecanemab (10 mg/kg, every two weeks) for three months. Cognitive assessments (Montreal Cognitive Assessment, Mini- Mental State Examination, Clinical Dementia Rating), eye movement tests (smooth pursuit, overlapping saccades, anti-saccades), and gait analysis under single-task and dual-task conditions were conducted at baseline and follow-up. Patient 1 (79 years old) showed stable cognitive function, significant improvement in multiple eye movement parameters, and partial improvement in gait under single-task conditions. Patient 2 (60 years old) did not follow up on cognitive function tests as scheduled and showed inconsistent changes in eye movement parameters, but improved selected gait measures under dual-task conditions, particularly a shorter turning time. Neither patient experienced Amyloid-Related Imaging Abnormalities or infusion-related adverse events during the infusion process.

CONCLUSION: This exploratory case report suggests that eye movement and gait analysis may be sensitive to short-term functional changes following lecanemab treatment, which were not consistently captured by traditional cognitive scales. These findings are hypothesis-generating and warrant further investigation in larger studies. Multimodal functional assessment may hold promise as a tool for monitoring early treatment effects in Alzheimer's disease.},
}

@article {pmid42381141,
year = {2026},
author = {Mehrabadi, S},
title = {The Role of Digital Health Technologies in Early Detection and Management of Alzheimer's Disease.},
journal = {Current Alzheimer research},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115672050415800251226061142},
pmid = {42381141},
issn = {1875-5828},
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and functional impairment, posing significant challenges for early detection and management. In recent years, digital health technologies have emerged as promising tools to enhance the diagnosis, monitoring, and treatment of AD. This review paper explores the multifaceted role of digital health technologies in the early detection and management of Alzheimer's disease. We examine the use of wearable devices that monitor cognitive function and daily activities, as well as mobile health applications designed for cognitive training and symptom tracking. Additionally, we analyze the impact of telehealth services in providing remote care, particularly for underserved populations. The integration of artificial intelligence and machine learning for analyzing behavioral and cognitive data to support early diagnosis and risk assessment is also discussed. Furthermore, we explore the concept of digital biomarkers and their potential to complement traditional diagnostic methods. Ethical considerations surrounding privacy, data security, and informed consent are addressed to ensure responsible implementation of these technologies. Finally, we highlight gaps in current research and propose future directions for integrating digital health technologies into Alzheimer's care, emphasizing the potential for personalized interventions tailored to individual patient needs. This review underscores the transformative potential of digital health to reshape Alzheimer's disease management and improve patient outcomes.},
}

@article {pmid42381155,
year = {2026},
author = {Zhao, S and Huang, Q and Nie, B and Zhang, T and Zuo, C and Zhang, G and Mao, G and Shan, B},
title = {Decomposition-based harmonization for quantitative PET imaging across scanners and radiotracers.},
journal = {Medical physics},
volume = {53},
number = {7},
pages = {e70545},
doi = {10.1002/mp.70545},
pmid = {42381155},
issn = {2473-4209},
support = {12575380//National Natural Science Foundation of China/ ; 12205329//National Natural Science Foundation of China/ ; 11975249//National Natural Science Foundation of China/ ; 12175268//National Natural Science Foundation of China/ ; },
mesh = {*Positron-Emission Tomography/instrumentation ; *Image Processing, Computer-Assisted/methods ; Phantoms, Imaging ; Humans ; Radioactive Tracers ; },
abstract = {BACKGROUND: Quantitative positron emission tomography (PET) is widely applied in oncology, neuroscience, and clinical practice. However, its quantitative accuracy is often compromised by systematic variability arising from differences in scanners, acquisition protocols, and radiotracers, which limits the reliability of multicenter studies.

PURPOSE: To develop and validate PETHarmony, a novel voxel-level harmonization framework for minimizing inter-scanner and inter-tracer variability.

METHODS: PETHarmony utilizes a linear neural network to model covariates and singular value decomposition to isolate and remove variability in voxel space. Its performance was assessed in four scenarios: (i) using paired 18 F $^{18}{
\rm F}$
-FBB PET/CT and PET/MR scans (N = 25, Huashan Hospital) to test the removal of scanner variability; (ii) using 20 repeated PET acquisitions of a NEMA NU-2 IQ phantom to validate absolute quantitative accuracy; (iii) using paired 18 F $^{18}{
\rm F}$
-FBP and 11 C $^{11}{
\rm C}$
-PiB scans from GAAIN (N = 46); and OASIS (N = 84) to evaluate cross-tracer consistency of cortical SUVR; and (iv) using unpaired multicenter data from ADNI (N = 471; 18 F $^{18}{
\rm F}$
-FBP, 18 F $^{18}{
\rm F}$
-FTP, 18 F $^{18}{
\rm F}$
-FDG) to assess the impact on Alzheimer's disease (AD) classification. All harmonization procedures were conducted using leave-one-out cross-validation or by training on unpaired data and applying the learned transformations to paired data.

RESULTS: PETHarmony effectively eliminated voxel-level discrepancies between PET/CT and PET/MR images (P < 0.05 $P < 0.05$ reduced to n.s.). Phantom validation demonstrated that recovery coefficient curves were restored and closely aligned with the reference line, indicating improved quantitative accuracy. For cross-tracer consistency, linear regression between 18 F $^{18}{
\rm F}$
-FBP and 11 C $^{11}{
\rm C}$
-PiB was markedly improved toward the line of identity (y = x, R 2 $^{2}$
= 1). Specifically, in the GAAIN cohort, the regression line improved from y = 0.52x + 0.52, R 2 ${\rm R}^
{2}$
= 0.89 to y = 0.93x + 0.13, R 2 $^{2}$
= 0.97. In the OASIS cohort, it improved from y = 0.51x + 0.55, R 2 ${\rm R}^
{2}$
= 0.87 to y = 0.95x + 0.06, R 2 ${\rm R}^
{2}$
= 0.95. Furthermore, PETHarmony improved multicenter AD classification accuracy by 15.3% (18 F $^{18}{
\rm F}$
-FBP), 18.3% (18 F $^{18}{
\rm F}$
-FTP), and 21.7% (18 F $^{18}{
\rm F}$
-FDG).

CONCLUSIONS: PETHarmony achieves robust voxel-level harmonization of multicenter PET data, significantly improving cross-scanner and cross-tracer consistency and enhancing diagnostic accuracy. It provides a practical solution for standardizing quantitative PET in multicenter oncology, neuroscience, and other clinical trials.},
}

*Positron-Emission Tomography/instrumentation
*Image Processing, Computer-Assisted/methods
Phantoms, Imaging
Humans
Radioactive Tracers

@article {pmid42381270,
year = {2025},
author = {Mirjalili, M and Brooks, H and Ma, C and Lee, A and Bikson, M and Voineskos, AN and Blumberger, DM and Fischer, CE and Flint, AJ and Herrmann, N and Kumar, S and Lanctôt, K and Mah, L and Mulsant, BH and Pollock, BG and Rajji, TK and , },
title = {Impact of Transcranial Direct Current Stimulation-Induced Electric Fields on Slowing Cognitive Decline in Older Adults With Mild Cognitive Impairment or Remitted Major Depressive Disorder: An Analysis of the PACt-MD Randomized Clinical Trial.},
journal = {Biological psychiatry},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.biopsych.2025.09.020},
pmid = {42381270},
issn = {1873-2402},
abstract = {BACKGROUND: Mild cognitive impairment and remitted major depressive disorder increase the risk of dementia. The PACt-MD (Prevention of Alzheimer's Dementia With Cognitive Remediation Plus Transcranial Direct Current Stimulation in Mild Cognitive Impairment and Depression) trial (NCT02386670) has shown that combined cognitive remediation (CR) and transcranial direct current stimulation (tDCS) improve cognitive outcomes by targeting executive function and presumably leveraging neurophysiological mechanisms. Our study investigated whether the magnitude of electric fields (EFs) induced by tDCS in the dorsolateral prefrontal cortex (DLPFC) predicted cognitive response in PACt-MD participants.

METHODS: Data from the 143 PACt-MD participants (mean [SD] age = 71.8 [6.34] years) who received active CR+tDCS and had brain magnetic resonance imaging (MRI) were analyzed. EFs were estimated using individual MRI with tDCS electrode placement at Fz (anode) and Iz (cathode). Participants were split into high- and low-EF groups based on the median. We used linear mixed models to assess the effect of EF in the left and right DLPFC on global cognitive decline, the primary outcome of PACt-MD, over 72 months. The global cognitive decline is the average of z scores on all tests on the neuropsychological battery.

RESULTS: EF magnitude in the left DLPFC was associated with global cognitive decline (likelihood ratio test: p = .026). Participants with high EF showed slower cognitive decline than those with low EF, irrespective of diagnosis and APOE ε4 status. No significant association was observed for the right DLPFC.

CONCLUSIONS: Our findings support that high EF in the DLPFC is associated with the efficacy of CR+tDCS. In future studies, tDCS dosing that results in a higher EF in the left DLPFC may improve the cognitive outcomes of CR+tDCS.},
}

@article {pmid42381275,
year = {2026},
author = {Yang, J and Mao, T and Gao, L},
title = {Role of incretins in Alzheimer's disease and their impact on behavioral aspects.},
journal = {Chinese medical journal},
volume = {},
number = {},
pages = {},
pmid = {42381275},
issn = {2542-5641},
abstract = {Recent studies highlight the therapeutic potential of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), two key incretin components, in neurodegenerative diseases, particularly Alzheimer's disease (AD). Although the incretin pathway may also affect other neurodegenerative conditions, this discussion focuses on AD. The therapeutic benefits are largely attributed to their role in enhancing energy metabolism. In vivo and in vitro studies have demonstrated that GLP-1 and GIP exert neuroprotective effects through the inhibition of oxidative stress, neuroinflammation, and neuronal apoptosis, while improving cellular metabolic function. Additionally, an emerging but often overlooked body of evidence suggests that incretin may influence human behaviors, such as eating habits, sleep patterns, physical activity, and vulnerability to substance addiction. These behavioral changes could, in turn, support neural regeneration through various molecular mechanisms. This article summarizes recent advancements in the understanding of incretin's influence on human behavior and its implications for AD.},
}

@article {pmid42381285,
year = {2026},
author = {Tan, H and Zhang, G and Du, C and Li, X and Bai, Y and Mao, L and Yang, F and Qi, Q and Zhao, N and Shi, W and Zhao, Y and Chang, M},
title = {The creation and verification of a detection model for mild cognitive impairment by employing eye-tracking and gait metrics.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261464176},
doi = {10.1177/13872877261464176},
pmid = {42381285},
issn = {1875-8908},
abstract = {BackgroundMild cognitive impairment is a prodromal stage of dementia, and early identification is crucial for prognosis.ObjectiveThis study aims to create and validate a machine learning model for diagnosing mild cognitive impairment (MCI) using eye movement and gait analysis data.MethodsTo facilitate model training and internal validation, a cohort of 235 patients was recruited from the Memory Clinic at Xi'an NO.3 Hospital between August 2024 and November 2025. In addition, data from 71 patients were randomly selected to form an independent test set. Feature selection was conducted using the Least Absolute Shrinkage and Selection Operator (LASSO) and multivariable logistic regression. Subsequently, various machine learning classifiers were compared. Model performance was assessed using metrics such as the area under the receiver operating characteristic curve (AUC) and decision curve analysis. To evaluate model interpretability, SHapley Additive exPlanations (SHAP) were employed.ResultsThe study involved 235 participants, divided into mild cognitive impairment (MCI) (n = 130) and healthy control (HC) (n = 105) groups. The final prediction model used four features: gait speed during a dual-task test, ground reaction force in a single-task test, antisaccade task accuracy, and noise rate in a saccade-to-pursuit task. The Gaussian Naive Bayes (GNB) classifier showed excellent performance with an AUC of 0.952 (95% CI: 0.923-0.981) in the validation group and 0.944 (95% CI: 0.912-0.967) in the test set.ConclusionsThe GNB model, combining eye movement and gait parameters, enables early MCI detection with high accuracy and practical clinical use.},
}

@article {pmid42381297,
year = {2026},
author = {Kim, JH and Lee, Y and Liao, Y and Schmid, CH and Kim, D and Trivedi, A and Meyers, DJ and Markides, K and Colon Vargas, M and Rosales, R and Crowe, M and Rivera-Hernandez, M},
title = {Diagnosis of Alzheimer's disease and related dementias and outmigration of older Puerto Rican Medicare Fee-for-service beneficiaries, 2012-2019.},
journal = {The journals of gerontology. Series B, Psychological sciences and social sciences},
volume = {},
number = {},
pages = {},
doi = {10.1093/geronb/gbag116},
pmid = {42381297},
issn = {1758-5368},
abstract = {OBJECTIVES: There is limited research on whether receiving a dementia diagnosis could prompt later-life migration, particularly among older Medicare beneficiaries in Puerto Rico. Prior research shows older Puerto Ricans are migrating to the mainland United States (U.S.), which may include those with an Alzheimer's Disease and Related Dementias (ADRD) diagnosis. This study examined yearly outmigration trends among older Puerto Ricans by exploring their movement patterns in 2011-2019.

METHODS: We used data from the Medicare Master Beneficiary Summary File and the Puerto Rican Community Survey and focused on Medicare Fee-for-Service enrollees aged 65 and older. The Chronic Conditions Warehouse algorithm was used to ascertain ADRD diagnosis, and migration was defined as the change of (end-of-year) residence from one year to the next. A linear probability model was used to calculate differences in the rate of outmigration between beneficiaries with and without ADRD.

RESULTS: Across the study period, the sample averaged 53,294 beneficiaries per year (43,819 [2019] to 66,625 [2012]), with 15% having a previous ADRD diagnosis each year. Overall, older Puerto Ricans previously diagnosed with ADRD were slightly more likely to move to the U.S. mainland compared to those without a diagnosis across the years (adjusted differences of b = 0.14∼0.42%), though differences were statistically significant in some years. For example, outmigration spiked (over 2.5%) among all older adults in the year of Hurricane Maria, regardless of health status.

DISCUSSION: Our results suggest that older Puerto Ricans with ADRD are more likely to migrate as they face challenges in aging in place.},
}

@article {pmid42381348,
year = {2026},
author = {Cary, GA and Young, JE and Rose, SE and Frankowski, H and Wilkins, H and Amirtha Ganesh, SS and Draper, J and Darvas, M and Bothwell, M and Jayadev, S and Reid, AN and Greenwood, A and Levey, AI and Leal, K and Carter, GW and Wiley, JC},
title = {Kat5 cKO mouse replicates biological domain signatures associated with Alzheimer's disease.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {7},
pages = {e71562},
doi = {10.1002/alz.71562},
pmid = {42381348},
issn = {1552-5279},
support = {//Emory-Sage-SGC-JAX TREAT-AD Center/ ; U54AG065187/AG/NIA NIH HHS/United States ; R01AG080585/AG/NIA NIH HHS/United States ; },
mesh = {Animals ; *Alzheimer Disease/genetics/metabolism ; Humans ; *Lysine Acetyltransferase 5/genetics/metabolism ; Mice ; Mice, Knockout ; *Hippocampus/metabolism ; Neurons/metabolism ; Amyloid beta-Protein Precursor/metabolism/genetics ; Transcriptome ; },
abstract = {INTRODUCTION: Alzheimer's disease (AD) can be caused by autosomal-dominant familial Alzheimer's disease (FAD) mutations in amyloid precursor protein (APP) or presenilin-1 and 2, which form an enzyme substrate complex. KAT5 binds to the APP intracellular domain. Recent reports of decreased γ-secretase activity in FAD mutants support KAT5 membrane sequestration.

METHODS: We compare the hippocampal transcriptome profiles of the Kat5 brain-specific knockout (KO) mouse to multiple AD datasets through alignment with the TREAT-AD AD biological domains. We examine KAT5 subcellular localization in human wild-type and AD neurons.

RESULTS: The Kat5 KO mouse demonstrates downregulation of synaptic genes, metabolic pathways, and upregulation of DNA replication and repair, cell cycle, and immune response genes. We see similar profiles in Kat5 and comparative AD datasets. KAT5 is restricted to the cytosol in human AD neurons.

DISCUSSION: This analysis supports the hypothesis that KAT5 nuclear signaling downstream of APP cleavage plays a pivotal role in neuronal homeostasis.},
}

Animals
*Alzheimer Disease/genetics/metabolism
Humans
*Lysine Acetyltransferase 5/genetics/metabolism
Mice
Mice, Knockout
*Hippocampus/metabolism
Neurons/metabolism
Amyloid beta-Protein Precursor/metabolism/genetics
Transcriptome

@article {pmid42381349,
year = {2026},
author = {Li, Y and Wang, D and Zhou, R and Yan, S and Wang, D and Wei, Y and Yao, H and Zhou, B and Lu, J and Wang, P and Liao, Z and Han, Y and Zhang, X and Zhang, Y and Liu, Y and Zhao, K and , },
title = {Human brain connectome profiles mediate the relationship between pathology burden and clinical phenotypes in Alzheimer's disease.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {7},
pages = {e71638},
doi = {10.1002/alz.71638},
pmid = {42381349},
issn = {1552-5279},
support = {T2425027//National Natural Science Foundation of China/ ; 82401858//National Natural Science Foundation of China/ ; 62201091//National Natural Science Foundation of China/ ; 2025KYQD22//Research Initiation Project for Introduced Talents of BUPT/ ; },
mesh = {Humans ; *Alzheimer Disease/pathology/genetics ; *Connectome ; *Brain/pathology ; *Cognitive Dysfunction/pathology ; Phenotype ; Female ; Aged ; Male ; Disease Progression ; Magnetic Resonance Imaging ; },
abstract = {INTRODUCTION: Mild cognitive impairment (MCI), a prodromal stage of Alzheimer's disease (AD), shows pronounced clinical heterogeneity poorly explained by pathology burden, representing a gap complicating prognosis. As the brain operates as a complex network for information integration, we hypothesized that connectome architecture mediates the link between AD pathology and clinical expression.

METHODS: We developed a framework integrating structural and functional connectomes from multi-center cohorts, performing connectome-based subtyping in MCI, with analyses of upstream pathology, downstream phenotypes, and transcriptomic associations.

RESULTS: This approach identified an "MCI-compromised" (MCI-C) subgroup characterized by extensive structural-functional connectomic disruption and an "MCI-preserved" (MCI-P) subgroup with relatively preserved connectome integrity. Despite comparable pathology, MCI-C demonstrated more severe neurodegeneration, accelerated cognitive decline, and elevated progression risk. Multiscale analyses linked these patterns to transcriptomic profiles of mitochondrial, synaptic, and neuroimmune processes.

DISCUSSION: These findings demonstrate that the connectome acts as a critical mediator, rather than a passive endophenotype, shaping AD clinical expression.},
}

Humans
*Alzheimer Disease/pathology/genetics
*Connectome
*Brain/pathology
*Cognitive Dysfunction/pathology
Phenotype
Female
Aged
Male
Disease Progression
Magnetic Resonance Imaging

@article {pmid42381352,
year = {2026},
author = {Panteleienko, L and Banerjee, G and Mallon, D and Chan, E and Fandler-Höfler, S and Oliver, R and Harvey, V and Jaunmuktane, Z and Collinge, J and Werring, DJ},
title = {Evidence for progressive neurodegeneration in iatrogenic cerebral amyloid angiopathy.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {7},
pages = {e71640},
doi = {10.1002/alz.71640},
pmid = {42381352},
issn = {1552-5279},
mesh = {Humans ; *Cerebral Amyloid Angiopathy/pathology/diagnostic imaging/etiology/complications ; Female ; Male ; Iatrogenic Disease ; Atrophy/pathology ; Magnetic Resonance Imaging ; Retrospective Studies ; Adult ; *Brain/pathology/diagnostic imaging ; Middle Aged ; Disease Progression ; Neuropsychological Tests ; Alzheimer Disease/pathology/etiology ; },
abstract = {INTRODUCTION: Iatrogenic transmission of amyloid beta can cause cerebral amyloid angiopathy (CAA) and Alzheimer's disease (AD), but the relationship between these phenotypes is unclear.

METHODS: We retrospectively analyzed standardized neuropsychological and neuroimaging data from 11 patients with iatrogenic CAA (iCAA). Brain MRI was assessed for medial temporal lobe atrophy (MTA), the posterior atrophy score for parietal atrophy, and global cortical atrophy (GCA).

RESULTS: All patients (mean age 42 ± 8.3 years) had childhood neurosurgery; 91% had confirmed cadaveric dura exposure. Six patients (55%) presented with intracerebral hemorrhage, and none showed MTA, parietal atrophy, or GCA at presentation. Over a median 5-year follow-up, 8/11 (73%) developed atrophy on at least one score, moderate to severe in three patients. Cognitive impairment was present in 9/11 (82%) at a median 3-year follow-up. AD was confirmed histopathologically in 2/4 (50%) examined cases.

DISCUSSION: Progressive brain atrophy and cognitive impairment are common in iCAA, suggesting frequent co-existing neurodegeneration and possible AD pathology. Vigilance for cognitive decline may enable earlier identification and management.},
}

Humans
*Cerebral Amyloid Angiopathy/pathology/diagnostic imaging/etiology/complications
Female
Male
Iatrogenic Disease
Atrophy/pathology
Magnetic Resonance Imaging
Retrospective Studies
Adult
*Brain/pathology/diagnostic imaging
Middle Aged
Disease Progression
Neuropsychological Tests
Alzheimer Disease/pathology/etiology

@article {pmid42381490,
year = {2026},
author = {Turk, KW and Marin, A and Karaca, M and Price, AM and Palumbo, R and Budson, AE},
title = {Reaction time as a performance validity measure in older adults with and without early-stage Alzheimer's disease.},
journal = {Applied neuropsychology. Adult},
volume = {},
number = {},
pages = {1-12},
doi = {10.1080/23279095.2026.2692527},
pmid = {42381490},
issn = {2327-9109},
abstract = {INTRODUCTION: Performance validity assessment is important in evaluating older adults with and without cognitive impairment. Performance validity tests (PVTs) such as the Test of Memory Malingering (TOMM) may inaccurately classify Alzheimer's disease (AD) patients as testing invalid despite genuine effort. We explored an alternative PVT using reaction time (RT).

METHODS: Healthy older controls (OCs; N = 20) and AD patients (N = 20) completed an auditory oddball task and the TOMM. Over two counterbalanced sessions, OCs performed honestly and simulated dementia; AD patients completed one honest session.

RESULTS: RT differed between OC honest and simulating conditions and between AD and OCs in both conditions. Using a composite reflecting RT differences between true positives and false alarms, simulators took more time generating false alarms than true positives compared to AD patients (p = 0.021; r = 0.364). The composite did not differ between OC honest and AD groups. The RT composite showed comparable specificity to the TOMM in classifying AD patients (80% vs. 75% for TOMM Trial 2 and 65% for Trial 1).

DISCUSSION: The RT composite performed similarly to the TOMM without relying as heavily on episodic memory. It warrants investigation as a complement to memory-based PVTs. Future studies should replicate these findings in larger, education-matched samples.},
}

@article {pmid42381527,
year = {2026},
author = {Lee, HJ and Yoon, B and Hong, YJ and Jeong, JH and Kim, S and Wang, MJ and Choi, SH and Ryu, JS and Kang, S and Park, KH and Yang, DW},
title = {APOE Genotype Modifies the Predictive Performance of Plasma Biomarkers for Amyloid Plaque Burden in Subjective Cognitive Decline.},
journal = {Journal of Korean medical science},
volume = {41},
number = {25},
pages = {e184},
doi = {10.3346/jkms.2026.41.e184},
pmid = {42381527},
issn = {1598-6357},
support = {P0018061/KIAT/Korea Institute for Advancement of Technology/Korea ; HI18C0530/MOHW/Ministry of Health and Welfare/Korea ; },
mesh = {Humans ; *Biomarkers/blood ; Amyloid beta-Peptides/blood ; *Cognitive Dysfunction/diagnosis/pathology/genetics ; Positron-Emission Tomography ; Glial Fibrillary Acidic Protein/blood ; Female ; Neurofilament Proteins/blood ; tau Proteins/blood ; ROC Curve ; Male ; *Plaque, Amyloid/pathology ; Retrospective Studies ; Aged ; Genotype ; *Apolipoprotein E4/genetics ; Peptide Fragments/blood ; Area Under Curve ; *Apolipoproteins E/genetics ; Alzheimer Disease/diagnosis/genetics ; Middle Aged ; },
abstract = {BACKGROUND: Apolipoprotein E (APOE) ε4 is a well-known risk factor for Alzheimer's disease (AD), with ε4 carriers exhibiting distinct clinical and biological characteristics compared to non-carriers. This study investigated whether the predictive performance of plasma biomarkers for amyloid positron emission tomography (PET) outcomes varies by APOE ε4 carrier status in individuals with subjective cognitive decline (SCD).

METHODS: We retrospectively analyzed baseline data from the Cohort Study to Identify Predictors for the Clinical Progression to Mild Cognitive Impairment or Dementia from Subjective Cognitive Decline. Plasma levels of the amyloid beta (Aβ) 42/40 ratio, glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and phosphorylated tau (pTau) 181 were quantified using Single Molecule Array technology. We assessed predictive performance of plasma biomarkers for amyloid PET outcomes using receiver operating characteristic analysis and linear regression models.

RESULTS: The study included 104 participants, with 20 APOE ε4 carriers and 84 non-carriers. Among ε4 carriers, NfL (area under the curve [AUC] = 0.909), GFAP (AUC = 0.904), and pTau181 (AUC = 0.828) showed the highest predictive accuracy. For non-carriers, the most predictive biomarkers were pTau181/Aβ42 (AUC = 0.872), Aβ42/Aβ40 (AUC = 0.794), and pTau181 (AUC = 0.761). Significant interactions between APOE and biomarkers were noted for GFAP (P = 0.005) and NfL (P = 0.010) in predicting amyloid plaque burden.

CONCLUSION: Plasma biomarkers exhibit differential predictive performance for amyloid pathology based on APOE genotype, with GFAP and NfL showing interaction with APOE genotype. These findings suggest the importance of considering APOE genotype when interpreting plasma biomarker results for AD diagnosis in individuals with SCD.

TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0003397.},
}

Humans
*Biomarkers/blood
Amyloid beta-Peptides/blood
*Cognitive Dysfunction/diagnosis/pathology/genetics
Positron-Emission Tomography
Glial Fibrillary Acidic Protein/blood
Female
Neurofilament Proteins/blood
tau Proteins/blood
ROC Curve
Male
*Plaque, Amyloid/pathology
Retrospective Studies
Aged
Genotype
*Apolipoprotein E4/genetics
Peptide Fragments/blood
Area Under Curve
*Apolipoproteins E/genetics
Alzheimer Disease/diagnosis/genetics
Middle Aged

@article {pmid42381622,
year = {2026},
author = {Preeti, and Akanksha, and Khurana, N},
title = {Pongamol as a multitarget neuroprotective candidate: an integrative analysis of in silico predictions and biological evidence.},
journal = {Natural product research},
volume = {},
number = {},
pages = {1-14},
doi = {10.1080/14786419.2026.2694726},
pmid = {42381622},
issn = {1478-6427},
abstract = {Pongamol, a bioactive flavonoid derived from Pongamia pinnata (Fabaceae), has gained attention as a potential therapeutic agent for neurological disorders. Neurodegenerative and neuropsychiatric conditions such as Alzheimer's, Parkinson's, epilepsy, anxiety and depression are driven by oxidative stress, neuroinflammation, mitochondrial dysfunction, apoptosis and neurotransmitter imbalance, while current treatments remain largely symptomatic. This study evaluates the neuroprotective potential of pongamol using integrated in silico and experimental approaches. SwissADME analysis revealed favourable pharmacokinetic properties, including good oral bioavailability, high gastrointestinal absorption, blood-brain barrier permeability and non-substrate behaviour for P-glycoprotein. Prediction of activity spectra of substances predictions indicated antioxidant, anti-inflammatory, anti-Alzheimer's, antiparkinsonian, GABAergic, nootropic and cytoprotective activities. Target mapping identified interactions with potassium channels, melatonin receptors, phosphodiesterase-4D and kynurenine pathway enzymes. These findings were further supported by limited experimental studies suggesting possible attenuation of oxidative stress, suppression of neuroinflammation, inhibition of apoptosis and improvement in cognitive and behavioural outcomes in disease models, highlighting pongamol as a promising multitarget neuroprotective candidate.},
}

@article {pmid42381975,
year = {2026},
author = {Zhang, C and Fang, D and Zhang, L},
title = {Brain Endothelial Glycocalyx as a Blood-Facing Translational Interface in Alzheimer's Disease: Beyond "Leaky" Barriers Toward Repair-First Stratification.},
journal = {Drug design, development and therapy},
volume = {20},
number = {},
pages = {619901},
pmid = {42381975},
issn = {1177-8881},
mesh = {Humans ; *Alzheimer Disease/metabolism/pathology/drug therapy ; *Glycocalyx/metabolism/pathology ; *Blood-Brain Barrier/metabolism/pathology ; Animals ; *Brain/metabolism/pathology ; },
abstract = {Alzheimer's disease (AD) pathogenesis is increasingly recognized as involving blood-brain barrier (BBB) and neurovascular unit (NVU) destabilization. The brain endothelial glycocalyx-a blood-facing glycan-rich interface-represents a critical but under-characterized determinant of BBB dysfunction in AD. In this review, we systematically reappraised glycocalyx abnormality mechanisms, distinguishing robust causal evidence from murine models from limited human observational data. We propose a four-dimensional interface-state framework (structural, glycosylation, transport, inflammatory) to stratify patients beyond binary "leaky versus intact" classifications. Glycocalyx deterioration in AD reflects compartmentalized remodeling (early mucin-domain depletion) rather than uniform shedding. A reversible therapeutic window exists in APOE4 carriers and mild cognitive impairment, but collapses with concurrent cerebral amyloid angiopathy (CAA) or amyloid-related imaging abnormalities (ARIA). Pathological glycocalyx disruption amplifies nonproductive vascular retention rather than parenchymal penetration. We advocate a hierarchical "repair-first, transport-engineering-second, exploitation-last" strategy. This repositions the glycocalyx as a decisive arbiter governing BBB-targeted interventions in AD, not merely a structural appendage.},
}

Humans
*Alzheimer Disease/metabolism/pathology/drug therapy
*Glycocalyx/metabolism/pathology
*Blood-Brain Barrier/metabolism/pathology
Animals
*Brain/metabolism/pathology

@article {pmid42382036,
year = {2026},
author = {Hofmann, A and Paczynski, M and Ponisio, MR and Saef, B and Roberts, JP and Powell, WJB and Gupta, A and Oh, I and Hofford, M and Posey, Z and Aldinger, M and Benzinger, TLS and Morris, JC and Snider, BJ and Schindler, SE},
title = {Performing multiple biomarker tests delays initiation of amyloid-targeting treatments.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {3},
pages = {e70387},
pmid = {42382036},
issn = {2352-8729},
abstract = {INTRODUCTION: With the clinical availability of amyloid-targeting treatments (ATTs), accurate and timely biomarker-based diagnosis of Alzheimer's disease (AD) has become increasingly important. Three AD biomarker modalities are commonly available in clinical practice: amyloid positron emission tomography (PET), cerebrospinal fluid (CSF) tests, and blood tests.

METHODS: We investigated the use and agreement of different biomarker modalities in a memory clinic. Further, we calculated the time until ATT initiation for patients who underwent a single test versus multiple biomarker tests.

RESULTS: The blood test agreed with amyloid PET in nine of 11 patients and CSF tests in all 14 patients. The median time from first clinic visit to ATT initiation was 4.7 months in 209 patients who underwent a single test and 8.1 months in 12 patients who underwent multiple tests.

DISCUSSION: Performing multiple biomarker tests delays initiation of ATT and should be restricted to patients with uncertain amyloid status following the first biomarker test.},
}

@article {pmid42382037,
year = {2026},
author = {Haque, M and Brookes, KJ and Shao, B},
title = {Anti-amyloid therapy eligibility in a longitudinal brain-donor cohort with post mortem confirmation.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {3},
pages = {e70400},
pmid = {42382037},
issn = {2352-8729},
abstract = {INTRODUCTION: Anti-amyloid therapies (AATs) for Alzheimer's disease (AD) demonstrate modest benefit in trials, but real-world eligibility remains uncertain. Requirements including biomarker confirmation and safety exclusions may limit access.

METHODS: Using the Brains for Dementia Research cohort, we linked longitudinal cognitive data with post mortem neuropathology to estimate trial-like AAT eligibility. Early stage was defined using harmonized cognitive thresholds. AD pathology required Thal amyloid phase ≥3 and Braak stage ≥IV. Exclusions were applied hierarchically: (1) vascular neuropathology, (2) anticoagulant use, and (3) apolipoprotein E (APOE) ε4/ε4 homozygosity.

RESULTS: Of 1230 participants, 945 had sufficient data; 232 had early, pathology-confirmed AD. Vascular pathology excluded 70.7%, anticoagulant use 19.1%, and APOE ε4/ε4 homozygosity 3.6% of remaining cases. Overall, 53 individuals (4.3% of those screened) were eligible. Eligibility declined with age and was driven primarily by vascular comorbidity.

DISCUSSION: Using a conservative pathology-anchored framework, only a small proportion of this older brain-donor cohort met trial-like eligibility criteria.},
}

@article {pmid42382038,
year = {2026},
author = {Yang, Y and Xu, J and Hou, Y and Zhou, Y and Saykin, AJ and Cheng, F},
title = {Deep contrastive learning framework identifies cell-type-specific drug targets in Alzheimer's disease.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {3},
pages = {e70406},
pmid = {42382038},
issn = {2352-8729},
abstract = {INTRODUCTION: Identifying disease-modifying drug targets is crucial for developing effective Alzheimer's disease (AD) treatments.

METHODS: We present a deep contrastive learning framework for cell type-specific AD-associated genes identification (alzCL). alzCL creates cell-type-specific representations of genes by integrating human brain single-nucleus RNA-sequencing data with the human protein-protein interactome, thereby capturing both genetic signatures and functional features.

RESULTS: By integrating human brain snRNA-seq data, alzCL outperforms the state-of-the-art models by 18% to 24% in area under the receiver operating characteristic curve. Via alzCL, we computationally identified 16, 164, and 221 AD-associated genes across astrocytes, microglia, and inhibitory neurons, respectively. Top prioritized genes (e.g., MAP3K5, P2RX4, and PRKD1) are significantly enriched in multiple AD-associated inflammatory and other pathobiological pathways. By integrating drug-target interaction data with alzCL-predicted AD-associated genes, we identified potential repurposable drugs for AD, including selonsertib and paroxetine.

DISCUSSION: AlzCL offers a deep contrastive learning framework for discovery of disease-associated genes and drug targets in AD.},
}

@article {pmid42382181,
year = {2026},
author = {DeDecker, K and Iroanyah, N and Morrison, A and Datta, J and Abejirinde, IO and Siu, CR and Stergiou-Dayment, C and Paron, S and Studzinski, CM},
title = {From community to policy: a frontline model for dementia assessment and brain health.},
journal = {Frontiers in dementia},
volume = {5},
number = {},
pages = {1821709},
pmid = {42382181},
issn = {2813-3919},
abstract = {Globally, dementia prevalence is projected to rise from approximately 55 million people in 2025 to 139 million by 2050. In Ontario, prevalence is estimated to reach 756,100 people by 2050-an increase of 202% since 2020-placing increasing strain on care partners, families, and health systems (Alzheimer Society of Canada, 2022). Throughout Ontario and Canada more broadly, existing pathways for cognitive screening, assessment, and diagnosis are constrained by limited primary care capacity, prolonged specialist wait times, and inequitable access, leaving many individuals without timely assessment or connection to supports. To help address these gaps, the Alzheimer Society of Ontario (ASO) and the Ontario Brain Institute (OBI) leveraged an existing community-delivered cognitive assessment process and enhanced it through the co-development of a provincial dementia registry-the first of its kind in Canada. This novel integrated approach embeds structured cognitive and functional assessment within community organizations, shares assessment results with primary care, and links standardized data to a provincial registry infrastructure. Together, this supports timely identification of cognitive concerns and enables the collection of a standardized minimum dataset-including cognitive, functional, demographic, and care-related information-across diverse populations. The dementia registry can serve as infrastructure to evaluate dementia-related innovations (including digital cognitive-screening tools) in real-world settings and support evidence generation to inform service planning and policy development, while strengthening earlier connection to supports and more coordinated care pathways for individuals and their care partners. This approach is aligned with emerging regulatory emphasis on real-world evidence (U.S. Food and Drug Administration, 2018; European Medicines Agency, 2021; Health Canada, 2019) and with Ontario's Improving Dementia Care in Ontario Act (2024), illustrating how co-designed, frontline-led approaches may bridge community needs and health system decision-making. Together, this work lays the groundwork for a scalable framework to advance equitable, person-centred dementia care in Ontario and beyond.},
}

@article {pmid42382525,
year = {2026},
author = {Bernhardt, AM and Höglinger, GU and Palleis, C},
title = {From clinical phenotypes to molecular stratification: early differential diagnosis of four-repeat tauopathies.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1801615},
pmid = {42382525},
issn = {1663-4365},
abstract = {Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are primary tauopathies defined by aggregation of four-repeat (4R) tau, yet early in vivo diagnosis remains limited by the dissociation between clinical phenotype and molecular pathology. Clinical presentations are heterogeneous, evolve over time, and frequently overlap with Alzheimer's disease, synucleinopathies, and mixed pathologies, particularly in corticobasal syndrome. As a result, clinical criteria provide structured phenotypic classification but have constrained specificity in early disease. This review synthesizes current evidence relevant to early diagnostic stratification in 4R tauopathies, integrating clinical criteria, supportive biomarkers of neurodegeneration, and emerging tau-directed molecular tools. The probabilistic value and limitations of contemporary criteria frameworks are discussed alongside the role of structural and functional imaging, dopaminergic imaging, and fluid markers as indicators of disease intensity and progression rather than molecular specificity. Advances in tau positron emission tomography and tau seed amplification assays are reviewed as biologically grounded approaches that directly interrogate aggregated and seed-competent tau species, with growing evidence for their potential contribution to individual-level stratification. Collectively, the literature supports a layered diagnostic approach in which clinical phenotype, supportive biomarkers, and tau-directed molecular measures are integrated to refine attribution of 4R tau pathology in vivo, a prerequisite for mechanism-based therapeutic development.},
}

@article {pmid42382677,
year = {2026},
author = {Siam, NH and Nasrin, N and Saiyara, S and Saha, H and Deb, DP and Islam, J},
title = {Medicinal Plants and Their Bioactive Phytochemicals as Emerging Therapeutic Strategies for Alzheimer's Disease: An Integrative Review of Preclinical and Clinical Evidence.},
journal = {Scientifica},
volume = {2026},
number = {},
pages = {6124916},
pmid = {42382677},
issn = {2090-908X},
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by β-amyloid deposition, tau hyperphosphorylation, mitochondrial dysfunction, oxidative stress, neuroinflammation, and blood-brain barrier disruption, collectively leading to widespread cortical and subcortical atrophy. Current FDA-approved pharmacotherapies, including acetylcholinesterase inhibitors and memantine, provide only modest symptomatic relief and fail to halt disease progression, underscoring the urgent need for alternative therapeutic approaches. Growing evidence highlights medicinal plants and their bioactive phytoconstituents as promising candidates for AD prevention and treatment because of their multitarget mechanisms, favorable safety profiles, and long history of traditional use. This review synthesizes extensive in vitro, in vivo, and clinical studies demonstrating the neuroprotective potential of plant extracts and isolated compounds that exert antioxidant, anti-inflammatory, antiamyloidogenic, anti-tau, cholinesterase-inhibitory, and synaptic-modulating effects. Key medicinal species, including Abelmoschus esculentus, Brassica oleracea, Cannabis sativa, Citrus reticulata, Lantana camara, Launaea taraxacifolia, Lawsonia inermis, Marrubium vulgare, Markhamia lutea, Persicaria minor, Pithecellobium dulce, Salvia aristata, Trigonella foenum-graecum, and Withania somnifera, show significant cognitive and neuroprotective benefits in experimental AD models. Phytochemicals such as sulforaphane, nobiletin, trigonelline, diosgenin, verbascoside, withaferin A, and withanolides strongly modulate the amyloid, tau, oxidative, and inflammatory pathways. Clinical trials further support the therapeutic potential of several plant-derived interventions for mild cognitive impairment and AD-related dementia. Collectively, these findings highlight medicinal plants and their active constituents as compelling complementary or translational strategies for AD management, warranting further mechanistic and clinical validation. This review aims to evaluate the neuroprotective potential of medicinal plants and their bioactive compounds in preventing and managing AD by summarizing evidence from in vitro, in vivo, and clinical studies.},
}

@article {pmid42382756,
year = {2026},
author = {Xing, JF and Mu, K and Yan, X and Yang, X and Zhang, D and Gao, W and Zhang, T and Yang, S and Wang, R and Zhang, W and Zhu, Y},
title = {Calibrating microglia states in Alzheimer's disease: decoding immune-metabolic networks and nano-targeted multicomponent therapies.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1843978},
pmid = {42382756},
issn = {1664-3224},
mesh = {*Alzheimer Disease/metabolism/immunology/therapy/pathology ; Humans ; *Microglia/metabolism/immunology/pathology/drug effects ; Animals ; Amyloid beta-Peptides/metabolism ; Metabolic Networks and Pathways ; },
abstract = {Alzheimer's disease treatment is shifting from pathology removal to regulating the brain microenvironment. Anti-Aβ monoclonal antibodies, such as lecanemab and donanemab, provide statistically significant disease-modifying effects but offer only modest cognitive improvement and pose safety risks, including amyloid-related imaging abnormalities. These results show that amyloid clearance is clinically relevant but not sufficient for full restoration of neuroimmune, metabolic, synaptic, and neurovascular balance. Microglia are now seen as central to Alzheimer's disease susceptibility and progression, existing along dynamic, spatially organized, sex-influenced, and genetically determined continua beyond a simple pro- or anti-inflammatory state. This review calls out three key drivers of microglial dysfunction: the TREM2-APOE lipid-sensing axis, complement-mediated synaptic elimination, and immunometabolic reprogramming-including glycolysis, mitochondrial damage, autophagy failure, NAD+ depletion, and innate immune signaling. We examine natural bioactive compounds, metabolic modulators, and biomimetic nanodelivery as promising, yet currently unproven, strategies for adjusting microglial state. Future therapies should incorporate both pathology removal and microenvironment protection, tailored by disease stage, genetic profile, sex, vascular risk, and microglial state-associated biomarkers.},
}

*Alzheimer Disease/metabolism/immunology/therapy/pathology
Humans
*Microglia/metabolism/immunology/pathology/drug effects
Animals
Amyloid beta-Peptides/metabolism
Metabolic Networks and Pathways

@article {pmid42382939,
year = {2026},
author = {Tamondong-Lachica, DR and Villanueva, CAG and Roxas-Timonera, M and Palileo-Villanueva, LM and , },
title = {Philippine Clinical Practice Guidelines for Periodic Health Examination: Lifestyle Interventions for Adults and Adolescents.},
journal = {Acta medica Philippina},
volume = {60},
number = {10},
pages = {71-89},
pmid = {42382939},
issn = {2094-9278},
abstract = {BACKGROUND: Lifestyle has a considerable impact on the prevalence and prognosis of noncommunicable diseases, which continue to be the leading causes of morbidity and mortality in the country and around the world. Cardiovascular disease, cancer, chronic lung disease, and diabetes are universally recognized as being significantly related to modifiable behaviors such as tobacco smoking, physical inactivity, and poor diet. Alzheimer's disease, multiple sclerosis, depression, and anxiety disorders have also been linked to lifestyle factors. Interventions to encourage healthy lifestyles and discourage hazardous behaviors among individuals aim to lower the burden of noncommunicable illnesses, improve survival, and improve individuals' and communities' overall quality of life.

OBJECTIVE: This Philippine clinical practice guideline (CPG) was developed to provide recommendations on nonpharmacologic approaches to promote healthy lifestyles among adults and adolescents.

METHODS: The Periodic Health Examination 2 (PHEX2) Lifestyle Advice Task Force proceeded through the preparation and prioritization, CPG generation, CPG appraisal, and implementation based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to CPG development recommended by the Department of Health (DOH). Nonpharmacological interventions of interest for this guide-line were clinical interventions that pertain to strategies done or recommended by individual providers to patients, likely in a clinic setting. Evidence review experts systematically reviewed existing clinical practice guidelines, appraised, and summarized the evidence. For questions on specific advice on healthy diet and physical activity, the ADAPTE methodology was applied after appraising existing CPGs with the AGREE II instrument. A multisectoral panel formulated recommendations through a formal consensus based on the evidence summaries. The CPG was externally reviewed prior to publication. In addition to general questions on financial and intellectual conflicts of interest (COI), typically associated with the pharmaceutical industry, specific questions related to lifestyle, such as involvement with weight loss clinics or programs, wellness centers, tobacco, and e-cigarettes, were included.

RESULTS: Nineteen (19) recommendations were made by the consensus panel, including adopting the WHO guidelines on physical activity and diet. During the consensus panel meetings, the impact of lifestyle-focused interventions on disease prevention was primarily considered, as well as the effect of these interventions on the prognosis of established diseases.

CONCLUSIONS: The Philippine Guidelines on PHEX Phase 2 Lifestyle Advice CPG is a systematic synthesis of evidence to address lifestyle or nonpharmacologic interventions in preventing diseases and promoting better health. More evidence on the effectiveness and safety outcomes of lifestyle-related interventions, direct evidence for the prevention of internet addiction and internet gaming disorder, longer follow-ups for effects of electronic nicotine delivery systems (ENDS), and studies on cost-effectiveness, patients' preferences, and health equity impact assessments are needed to make more robust recommendations on a healthy lifestyle.},
}

@article {pmid42383056,
year = {2026},
author = {Liu, DZ and Cheng, GL and Hu, CF and Li, RY and Yang, CC and Chen, NC and Li, X and Jiang, DY and Chang, JY},
title = {Alternative splicing-based therapeutics for neurodegenerative diseases: a dual-database bibliometric and NLP-driven analysis (2000-2025).},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1849726},
pmid = {42383056},
issn = {2296-858X},
abstract = {BACKGROUND: Neurodegenerative diseases (NDDs) are driven by complex molecular dysregulation, among which aberrant alternative splicing (AS) has emerged as a critical pathogenic mechanism. Despite the rapid development of splicing-targeted therapeutics, including antisense oligonucleotides (ASOs) and small molecules, comprehensive big-data syntheses mapping this translational landscape remain scarce. This study systematically analyzes the global research trends, conceptual frameworks, and clinical evolution of AS-based therapeutics for NDDs using an integrated bibliometric and natural language processing (NLP) approach.

METHODS: A dual-database retrieval strategy utilized the Web of Science Core Collection (WoSCC) and PubMed. The analysis targeted literature published between January 1, 2000, and December 31, 2025. A primary dataset of 620 records was extracted from WoSCC for comprehensive bibliometric mapping and Latent Dirichlet Allocation (LDA) topic modeling. A parallel analysis incorporated 10 targeted clinical trials and randomized controlled trials (RCTs) from PubMed using CLARA clustering to characterize high-evidence research. Bibliometric analyses, encompassing network topologies, citation bursts, and keyword evolution, were visualized using VOSviewer, CiteSpace, SCImago, and R.

RESULTS: Publication output exhibited sustained linear growth from 2000 to 2025. The United States and Western Europe emerged as the dominant collaborative hubs, while China exhibited high productivity but limited international integration. LDA topic modeling identified three core conceptual axes: molecular mechanisms, disease-specific pathological models (e.g., ALS, Alzheimer's, and SMA), and translational methodological frameworks. Keyword trajectories delineated a transition from fundamental in vitro exploration to in vivo models, culminating in clinical "drug discovery" and "RNA" therapeutics. CLARA clustering of clinical trials demonstrated a stark concentration of splicing-modifying interventions in pediatric spinal muscular atrophy (SMA), revealing a dual-track paradigm of supportive care and molecular interventions.

CONCLUSION: This multi-database bibliometric and NLP-driven study delineates the structural landscape of AS-based therapeutics for NDDs. It identifies a definitive paradigm shift from descriptive molecular biology to clinically actionable splicing interventions. These insights highlight the necessity to expand targeted RNA platforms beyond SMA into adult neurodegenerative populations, providing a strategic roadmap for future translational research.},
}

@article {pmid42383163,
year = {2026},
author = {van Alphen, JL and Pozzi, FE and Booij, J and Barkhof, F and Ten Kate, M and Teunissen, CE and van der Flier, WM and Lemstra, AW},
title = {Longitudinal biomarkers in dementia with Lewy bodies: A systematic review and meta-analysis.},
journal = {Clinical parkinsonism & related disorders},
volume = {15},
number = {},
pages = {100470},
pmid = {42383163},
issn = {2590-1125},
abstract = {INTRODUCTION: Dementia with Lewy bodies (DLB) is the second most prevalent neurodegenerative dementia. It is clinically and biologically heterogeneous, yet longitudinal biomarker studies assessing different aspects of neuropathological processes in DLB are scarce. We systematically reviewed the literature to identify biomarkers suitable for tracking disease progression in DLB and to evaluate potential outcome measures for clinical trials by examining which biomarkers show longitudinal changes correlating with clinical progression.

METHODS: Following PRISMA guidelines, we searched CENTRAL, MEDLINE, Embase, Scopus, and Web of Science for longitudinal biomarker studies in DLB (sample size ≥10, follow-up duration ≥6 months). We conducted meta-analysis of three structural MRI-studies assessing whole-brain atrophy.

RESULTS: Of 9162 titles screened, 17 studies met selection criteria including ±460 patients with MCI-LB/DLB. 15 studies included imaging biomarkers (MRI, SPECT, PET) and two studies included fluid biomarkers (plasma, CSF). Except for DAT-SPECT, most studies addressed non-DLB specific neurodegeneration or Alzheimer's disease (AD) pathology. Structural MRI-studies showed greater longitudinal atrophy in AD and mixed DLB + AD versus DLB and controls. Meta-analysis confirmed that DLB-patients were comparable to controls (p = 0.37), but showed lower atrophy rates than AD (p = 0.01). Amyloid-PET and biofluid studies suggested that amyloid accumulation follows typical progression, even in non-AD diagnoses. DAT-SPECT and FDG-PET demonstrated longitudinal changes correlating with clinical progression, showing promise as monitoring biomarkers.

CONCLUSION: No single biomarker currently suffices to track disease progression in DLB. DAT-SPECT and FDG-PET showed promise, but further research is warranted on these and alternative, more disease-specific, accessible and feasible modalities to improve disease monitoring in future clinical trials.},
}

@article {pmid42383392,
year = {2026},
author = {Sabouri, E and Shahmoradi, T and Keshvari, NZ and Khodaee, P and Saleki, K and Rezaei, N},
title = {Role of Toll-like receptors and oral-gut-brain axis in neurodegenerative and neuropsychiatric disorders.},
journal = {Reviews in the neurosciences},
volume = {},
number = {},
pages = {},
pmid = {42383392},
issn = {2191-0200},
abstract = {The oral-gut-brain axis is a path connecting the gastrointestinal tract and the central nervous system (CNS). The gut microbiota influences the immune system, metabolism, and nerve cells through the production of neurotransmitters and microbial metabolites that can cross the blood-brain barrier (BBB). The interplay between neuroinflammation and altered oral and gut microbiota is a bidirectional complex path modulated by inflammatory mediators. Recent studies suggest a potential role for Toll-like receptor (TLR) signaling pathways in the induction of neuroinflammation via the oral-gut-brain axis. As neuroinflammation is one of the key elements in the pathophysiology of neurodegenerative and neuropsychiatric disorders, this review was conducted to reflect on the pathophysiological pathways and clinical evidence on the role of TLR and inflammasome signaling pathways via oral-gut-brain axis in neurodegenerative diseases such as cognitive impairment, Alzheimer's disease, Multiple sclerosis, Parkinson's disease, Huntington's disease, and Amyotrophic lateral sclerosis, and psychiatric disorders such as major depressive disorder, anxiety disorders, schizophrenia, bipolar disorders, and Autism spectrum disorders. Because the contributing factors have not been fully understood yet, further studies could help provide novel therapeutic opportunities.},
}

@article {pmid42383593,
year = {2026},
author = {Kpetou, R and Raposo Pereira, F and Segobin, S and La Corte, V and Villain, N and Groussard, M and Jauny, G and Platel, H and Hinault, T and , },
title = {Multilayer brain connectivity and long-term cognitive changes in individuals at risk for Alzheimer's disease.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261464453},
doi = {10.1177/13872877261464453},
pmid = {42383593},
issn = {1875-8908},
abstract = {BackgroundAmong aging individuals, some develop Alzheimer's disease (AD) while others remain cognitively stable. Understanding how structural and functional brain changes interact, could clarify this heterogeneity particularly among individuals at increased risk for AD.ObjectiveThis study aims to explore how structure-function connectivity changes relate to subsequent long-term cognitive trajectories in older adults with SMC and varying amyloid burden.MethodsWe analyzed data from the INSIGHT-preAD cohort, which includes older individuals with subjective cognitive complaints followed neuropsychologically over five years. Multiplex connectome integrating resting-state EEG functional connectivity and diffusion-weighted imaging-based structural connectivity was used to characterize brain network organization. We computed the multiplex participation coefficient (PC) as an index of structure-function similarity and examined its association with individual cognitive trajectories across the follow-up period.ResultsSignificant differences in multiplex connectivity were observed among amyloid positive participants who later progressed to AD compared to amyloid positive stable (e.g., non-progressors) and amyloid negative controls. Specifically, higher PC values in the delta band were observed in amyloid positive individuals who later developed AD. This pattern, particularly within the default mode network, was associated with subsequent cognitive decline suggesting that delta band structure-function similarity may represent a potential candidate marker of cognitive vulnerability and progression in AD.ConclusionsMost studies investigating AD have primarily examined functional or structural connectivity separately. By integrating both modalities using a multiplex approach, our study provides interesting preliminary evidence that structure-function connectivity may capture network-level changes associated with cognitive trajectories along AD continuum.},
}

@article {pmid42383821,
year = {2026},
author = {Zheng, Y and Kang, L and Yang, X and Zhou, R and Chen, H and Wang, W and Xu, X and Xu, W and Liu, J and Li, B and Deng, Y},
title = {Stage-dependent relationship between sleep duration and cortical tau deposition in cognitively impaired individuals: A cross-sectional study.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261462419},
doi = {10.1177/13872877261462419},
pmid = {42383821},
issn = {1875-8908},
abstract = {BackgroundChanges in sleep characteristics are critical in the course of Alzheimer's disease (AD).ObjectiveWe aimed to explore the relationship between sleep duration and tau pathology progression in patients with AD and mild cognitive impairment (MCI).MethodsThis cross-sectional study included 172 patients (70 with MCI and 102 with AD). Sleep duration and disturbances were assessed through standardized questionnaires, while tau deposition and cerebrospinal fluid clearance were evaluated using tau-PET and diffusion tensor image analysis along the perivascular space (DTI-ALPS), along with comprehensive cognitive assessments. The data were adjusted for variables such as demographic factors, clinical symptoms, and medications.ResultsSleep duration showed a positive association with tau deposition in the MCI stage (total sleep: β = 0.18, p = 0.014; nighttime sleep: β = 0.20, p = 0.007) but negatively associated in the AD stage (total sleep: β = -0.18, p = 0.039; nighttime sleep: β = -0.20, p = 0.039). Patients with sleep disturbances demonstrated lower tau burdens (group difference = 0.62, p = 0.005). Mediation analysis revealed a significant indirect effect of depression in the sleep-tau relationship (total sleep: β = -0.26, p = 0.040; nighttime sleep: β = -0.24, p = 0.040).ConclusionsThis study first revealed the stage-dependent characteristics of sleep-tau relationships, highlighting the MCI stage as a critical research focus.Clinical TrialThe study was registered with ClinicalTrials.gov (NCT05623124). URL: https://clinicaltrials.gov/study/NCT05623124.},
}

@article {pmid42383918,
year = {2026},
author = {Chambliss, AB},
title = {The Emerging Role of Blood-Based Biomarkers in Predicting Alzheimer's Disease.},
journal = {The journal of applied laboratory medicine},
volume = {11},
number = {4},
pages = {997},
doi = {10.1093/jalm/jfag054},
pmid = {42383918},
issn = {2576-9456},
}

@article {pmid42383928,
year = {2026},
author = {Romero-Murillo, S and Cartas-Cejudo, P and De Miguel, M and Extramiana, L and Fernandez-Irigoyen, J and Santamaria, E},
title = {Unveiling the post translational modification code in Alzheimer's pathogenesis: crosstalk between phosphorylation and acetylation.},
journal = {Expert review of proteomics},
volume = {},
number = {},
pages = {},
doi = {10.1080/14789450.2026.2698463},
pmid = {42383928},
issn = {1744-8387},
}

@article {pmid42384085,
year = {2026},
author = {Sanchez, DL and Bennett, IJ},
title = {Normalization method for relative cerebral blood flow influences sex and cognitive status effects in nondemented older adults.},
journal = {Brain imaging and behavior},
volume = {20},
number = {4},
pages = {},
pmid = {42384085},
issn = {1931-7565},
mesh = {Humans ; Male ; Female ; *Cerebrovascular Circulation/physiology ; Aged ; *Cognitive Dysfunction/physiopathology/diagnostic imaging ; *Cognition/physiology ; Sex Characteristics ; Magnetic Resonance Imaging/methods ; Aged, 80 and over ; *Brain/diagnostic imaging/physiopathology ; Perfusion Magnetic Resonance Imaging ; Hippocampus/diagnostic imaging ; Neuropsychological Tests ; },
abstract = {Cerebral blood flow (CBF) is lower in males than females in cortical gray matter, but these sex effects are unknown in the hippocampus. Potential interactions between sex and cognitive status on CBF, which may contribute to the greater risk for females to develop mild cognitive impairment (MCI), are also understudied. Moreover, these effects may vary when regional CBF is normalized relative to individual differences in reference region CBF (residual rCBF) compared to more common difference scores (traditional rCBF). The current study examined effects of sex, cognitive status, and their interaction on residual and traditional rCBF in the cortical lobes and hippocampus in 111 cognitively unimpaired older adults (CU; 61.3%) and 49 older adults diagnosed with MCI (46.9% female) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) with T1-weighted and perfusion-weighted magnetic resonance imaging data. As expected, rCBF was significantly lower in males than females in the occipital lobe, p = 0.010, but was unexpectedly significantly higher in males than females in the hippocampus, p < 0.001, with the sex effect being larger for traditional rCBF in the occipital lobe and residual rCBF in the hippocampus, ps < 0.024. Cognitive status significantly interacted with rCBF metric and region, ps < 0.014, but yielded no significant between group difference for any metric in any region, ps > 0.06. There were no significant interactions between sex and cognitive status, ps > 0.10. Taken together, these findings indicate that effects of sex on rCBF are region specific, independent of cognitive status, and vary with rCBF normalization method in non-demented older adults.},
}

Humans
Male
Female
*Cerebrovascular Circulation/physiology
Aged
*Cognitive Dysfunction/physiopathology/diagnostic imaging
*Cognition/physiology
Sex Characteristics
Magnetic Resonance Imaging/methods
Aged, 80 and over
*Brain/diagnostic imaging/physiopathology
Perfusion Magnetic Resonance Imaging
Hippocampus/diagnostic imaging
Neuropsychological Tests

@article {pmid42384109,
year = {2026},
author = {Spallazzi, M and Zilioli, A and Ruffini, L and Imbimbo, BP},
title = {Number needed to treat and harm for lecanemab and donanemab in early Alzheimer disease.},
journal = {Journal of neurology},
volume = {273},
number = {7},
pages = {},
pmid = {42384109},
issn = {1432-1459},
}

@article {pmid42384167,
year = {2026},
author = {Bi, Q and Zhang, L and Zhang, J and Wang, X and Zuo, C and Zhao, S and Wang, Z and Zhao, Z and Wan, H},
title = {Glucagon-like peptide-1 receptor agonists in neurodegenerative diseases: a bibliometric analysis of global research trends and research hotspots from 2006 to 2025.},
journal = {Naunyn-Schmiedeberg's archives of pharmacology},
volume = {},
number = {},
pages = {},
pmid = {42384167},
issn = {1432-1912},
abstract = {This study aimed to systematically characterize the global research landscape, collaboration patterns, knowledge structure, and emerging hotspots of glucagon-like peptide-1 receptor agonists in neurodegenerative diseases using bibliometric methods. Publications related to glucagon-like peptide-1 receptor agonists and neurodegenerative diseases were retrieved from the Web of Science Core Collection from 2006 to 2025. Only English-language articles and reviews were included. Bibliometric analyses were performed using Bibliometrix, VOSviewer, and CiteSpace to evaluate annual publication trends, country and institutional contributions, author collaborations, journal distribution, citation structures, keyword co-occurrence, thematic evolution, and citation bursts. A Scopus-based sensitivity analysis was conducted to assess the robustness of the main bibliometric findings. A total of 1,202 publications were included, with annual output increasing from 2 in 2006 to 241 in 2025, particularly after 2020. China, the USA, and England were the leading contributors and major collaboration hubs. Shanxi Medical University, Lancaster University, and the National Institute on Aging were among the most productive institutions, while major journals included International Journal of Molecular Sciences, Neuropharmacology, European Journal of Pharmacology, Frontiers in Endocrinology, Frontiers in Pharmacology, and Journal of Alzheimer's Disease. Keyword and citation analyses indicated a thematic shift from exendin-4, Alzheimer's disease, Parkinson's disease, and neuroprotection toward semaglutide, neuroinflammation, cognitive impairment, clinical efficacy, evidence synthesis, and combination therapy. Research on glucagon-like peptide-1 receptor agonists in neurodegenerative diseases has expanded rapidly over the past two decades. Current bibliometric evidence suggests that this field has evolved from preclinical exploration toward broader translational and clinical research, with increasing attention to neuroinflammation, metabolic dysfunction, cognitive outcomes, and newer incretin-based therapies. However, the therapeutic implications of glucagon-like peptide-1 receptor agonists for neurodegenerative diseases remain to be further validated by high-quality mechanistic studies and well-designed clinical trials.},
}

@article {pmid42384283,
year = {2026},
author = {Mostafa, SS and Mohammed, RA and Abbas, AY and Othman, MA},
title = {The protective role of melatonin on the brain in a rat model of Alzheimer's disease.},
journal = {Metabolic brain disease},
volume = {41},
number = {1},
pages = {},
pmid = {42384283},
issn = {1573-7365},
mesh = {Animals ; *Melatonin/pharmacology/therapeutic use ; *Alzheimer Disease/chemically induced/drug therapy/metabolism/pathology/prevention & control ; Male ; Rats ; *Neuroprotective Agents/pharmacology/therapeutic use ; *Brain/drug effects/metabolism/pathology ; Disease Models, Animal ; Aluminum Chloride ; Maze Learning/drug effects ; Microglia/drug effects/metabolism ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha/metabolism ; },
abstract = {Alzheimer's disease is an age-related neurodegenerative disorder characterized by progressive cognitive decline and multiple biochemical and structural abnormalities in the brain. Accumulating evidence suggests that aluminum exposure may contribute to neurodegenerative process including those observed in AD and was linked to neuronal damage and cognitive impairment. Melatonin (Mel) is a neurohormone that regulates circadian rhythm and possesses antioxidant, anti-inflammatory and neuroprotective properties. The current study investigated the potential protective roles of Mel in a rat model of AD induced by aluminum chloride (AlCl3). Forty adult male rats were divided into 4 experimental groups: a control group, an AlCl3-treated group, an AlCl3+Mel-treated group, and a Mel-only group. AlCl3 was administered orally for four weeks. Cognitive performance and spatial learning were assessed using Morris water maze test. Plasma levels of the pro inflammatory cytokines; interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) were measured using enzyme linked immunosorbent assay. Histopathological examination of the frontal cortex was performed using hematoxylin and eosin staining, and immunohistochemistry was conducted using the neuronal marker NeuN, microglial marker Iba1, and inflammatory markers IL-6 and TNF-α. Mel treatment significantly improved learning and memory performance in the Morris water maze test. It also reduced plasma levels of IL-6 and TNF-α. Using immunohistochemistry, Mel increased NeuN expression, while reducing Iba1, IL-6 and TNF-α expression. These findings showed that Mel attenuated frontal cortical neurodegeneration and neuroinflammation in this model of AD, suggesting that Mel may represent a promising neuroprotective therapeutic strategy for AD.},
}

Animals
*Melatonin/pharmacology/therapeutic use
*Alzheimer Disease/chemically induced/drug therapy/metabolism/pathology/prevention & control
Male
Rats
*Neuroprotective Agents/pharmacology/therapeutic use
*Brain/drug effects/metabolism/pathology
Disease Models, Animal
Aluminum Chloride
Maze Learning/drug effects
Microglia/drug effects/metabolism
Rats, Sprague-Dawley
Tumor Necrosis Factor-alpha/metabolism

@article {pmid42384500,
year = {2026},
author = {Wang, Y and Jiao, CN and Gao, YL and Cui, XC and Zheng, CH and Liu, JX},
title = {Exploring Complex Genetic Mechanisms in Brain Imaging Genetics via a New Multi-task Learning Method.},
journal = {IEEE transactions on computational biology and bioinformatics},
volume = {PP},
number = {},
pages = {},
doi = {10.1109/TCBBIO.2026.3709159},
pmid = {42384500},
issn = {2998-4165},
abstract = {Brain imaging genetics generally combines genotype data with brain structure and functional measures to investigate the genetic basis of neurological disorders. Multimodal brain imaging data carry different but complementary information, which can clearly measure the same brain. Multi-task sparse canonical correlation analysis (MTSCCA) is often used to analyze the bi-multivariate correlation between genotype data and multimodal imaging features; however, it lacks the capacity to identify class-specific biomarkers and to deeply capture complex genetic mechanisms. In this paper, a linear discrimination and decomposition method based on MTSCCA (LDMTSCCA) is proposed to solve above problems. Specifically, LDMTSCCA first extracts disease-related genetic information using sparse linear discriminant analysis, and then employs parameter decomposition to learn multi-level expression patterns of genetic loci. To better explore intricate genetic mechanisms, LDMTSCCA jointly incorporates disease states, parameter decomposition, and network connectivity constraints into the association analysis between multilocus genetic information and multimodal neuroimaging phenotypes. The proposed method is compared with the traditional single task, multi-task, multi-view, and deep learning-based canonical correlation analysis methods in Alzheimer's Disease Neuroimaging Initiative, which shows that LDMTSCCA not only achieves the highest canonical correlation coefficients but also identifies multi-level biomarkers.},
}

@article {pmid42384774,
year = {2026},
author = {Walker, KA and Blew, C and Duggan, MR and Joynes, C and Gomez, GT and Drouin, S and Cordon, J and Chen, J and Zhang, J and File, B and Nanasi, T and Lehallier, B and Oh, H and Surapaneni, A and Grams, ME and Palta, P and Sullivan, KJ and Pichet Binette, A and Wu, L and Zhu, J and Leonard, H and Singleton, AB and Fornage, M and Gottesman, RF and Mosley, TH and Chatterjee, N and Boerwinkle, E and Ferrucci, L and Coresh, J and Schlosser, P},
title = {Alzheimer's disease proteome-wide association study implicates adaptive immunity and identifies risk genes LILRB1 and SIRPA.},
journal = {Science translational medicine},
volume = {18},
number = {856},
pages = {eadx4852},
doi = {10.1126/scitranslmed.adx4852},
pmid = {42384774},
issn = {1946-6242},
mesh = {Humans ; *Alzheimer Disease/genetics/immunology ; *Genome-Wide Association Study ; *Genetic Predisposition to Disease ; Quantitative Trait Loci/genetics ; *Proteome/metabolism ; *Adaptive Immunity/genetics ; *Receptors, Immunologic/genetics ; Risk Factors ; *Antigens, CD/genetics ; },
abstract = {The rapid expansion of plasma proteomic data and protein quantitative trait loci (pQTLs) provides an opportunity to identify genes that confer disease risk through their effect on plasma protein abundance. We conducted an Alzheimer's disease (AD) proteome-wide association study (PWAS) integrating publicly available plasma cis-pQTL data (1348 European American and 1385 African American genetically determined protein models) with AD dementia GWAS summary statistics. Whereas the African American PWAS identified one candidate [apolipoprotein E (APOE)] and multiple suggestive genes, the European American PWAS identified 18 genes with putative causal relationships with AD through cis regulation of plasma protein abundance. Thirteen of these candidate genes were additionally supported by colocalization and complementary causal-inference analyses such as summary data-based Mendelian randomization. Four of these proteins were not previously detected in AD GWAS [complement decay-accelerating factor (CD55), leukocyte immunoglobulin-like receptor B1 (LILRB1), scavenger receptor class A member 5 (SCARA5), and signal regulatory protein alpha (SIRPA)]. A subset of candidate gene-associated proteins was associated with 8- and 20-year dementia risk, markers of AD pathology, and a CSF proteomic signature enriched for immune and metabolic processes. Putative causal proteins were enriched for adaptive (lymphocyte-mediated) immunity and, compared with GWAS candidates, showed less enrichment for synaptic and amyloid regulatory processes. LILRB1 and SIRPA, two immunoregulatory proteins not previously implicated in AD GWAS, showed the strongest mechanistic link to AD in the European American PWAS. These results shed additional light on AD etiology and enable the prioritization of potential AD therapeutic targets in peripheral circulation.},
}

Humans
*Alzheimer Disease/genetics/immunology
*Genome-Wide Association Study
*Genetic Predisposition to Disease
Quantitative Trait Loci/genetics
*Proteome/metabolism
*Adaptive Immunity/genetics
*Receptors, Immunologic/genetics
Risk Factors
*Antigens, CD/genetics

@article {pmid42384796,
year = {2026},
author = {Hu, H and Guo, D and Pu, Y and Abuduaini, Y and Wang, X and Francks, C and Thompson, PM and Kong, XZ},
title = {Variations of global brain asymmetry are associated with aging and related diseases.},
journal = {Science advances},
volume = {12},
number = {27},
pages = {eadu9309},
doi = {10.1126/sciadv.adu9309},
pmid = {42384796},
issn = {2375-2548},
mesh = {Humans ; *Aging/pathology ; *Brain/physiopathology/pathology/diagnostic imaging ; Female ; *Functional Laterality ; *Alzheimer Disease/physiopathology/diagnostic imaging/genetics/pathology ; Male ; Magnetic Resonance Imaging ; *Parkinson Disease/physiopathology/diagnostic imaging/genetics/pathology ; Aged ; Cognition ; Machine Learning ; },
abstract = {Lateralization is a hallmark of brain organization, yet the structural basis underlying this phenomenon remains a critical, unresolved question in cognitive and systems neuroscience. In this study, we applied multivariate machine learning techniques to investigate variations of global brain asymmetry and their associations with cognitive functions, aging, and aging-related diseases, using large-scale datasets. Our findings revealed substantial and previously unknown structural differences between the hemispheres, and established key associations between structural asymmetries and lateralized functions. At the population level, we identified unique aging trajectories of hemispheric differences and uncovered diagnosis-specific variations in patients with Alzheimer's and Parkinson's disease, and in APOE ε4 carriers at genetic risk. Notably, we identified a "left hemi-aging" pattern that challenges the conventional "right hemi-aging" model. Together, these results advance our understanding of functional lateralization in the human brain and highlight the potential of global brain asymmetry as a biomarker for brain aging and related diseases.},
}

Humans
*Aging/pathology
*Brain/physiopathology/pathology/diagnostic imaging
Female
*Functional Laterality
*Alzheimer Disease/physiopathology/diagnostic imaging/genetics/pathology
Male
Magnetic Resonance Imaging
*Parkinson Disease/physiopathology/diagnostic imaging/genetics/pathology
Aged
Cognition
Machine Learning

@article {pmid42385110,
year = {2026},
author = {Lichter, DG},
title = {Neuropathogenesis of Seizures in Patients With Alzheimer Disease and Lewy Body Dementia: Is There a Difference, and Does It Matter?.},
journal = {Neurology},
volume = {107},
number = {2},
pages = {e218344},
doi = {10.1212/WNL.0000000000218344},
pmid = {42385110},
issn = {1526-632X},
}

@article {pmid42385111,
year = {2026},
author = {Tort-Merino, A and Esteller-Gauxax, D and Pérez-Millan, A and Castellví, M and Bosch, B and Sánchez-Rodríguez, MM and Rigol, A and Rubio, G and Morante-Serra, C and Mir-Sala, L and Patricio, V and Juncà-Parella, J and Torres-Coll, J and Guillén, N and Martín-Sobrino, I and Massons, M and Canasto, P and Alcón, D and Fernández-Villullas, G and Puey, R and Comas-Albertí, A and Antonell, A and Borrego-Écija, S and Falgàs, N and Sánchez-Valle, R and Lladó, A and Balasa, M},
title = {Neuropsychological Profile and Cognitive Trajectories of Patients With Biomarker Evidence of Alzheimer Disease or Dementia With Lewy bodies.},
journal = {Neurology},
volume = {107},
number = {2},
pages = {e218201},
doi = {10.1212/WNL.0000000000218201},
pmid = {42385111},
issn = {1526-632X},
mesh = {Humans ; Female ; *Alzheimer Disease/psychology/blood/complications ; *Lewy Body Disease/psychology/blood/complications ; Male ; Aged ; Neuropsychological Tests ; Biomarkers/blood/cerebrospinal fluid ; Longitudinal Studies ; Retrospective Studies ; alpha-Synuclein/cerebrospinal fluid ; *Cognition ; tau Proteins/blood/cerebrospinal fluid ; Amyloid beta-Peptides/cerebrospinal fluid/blood ; Aged, 80 and over ; },
abstract = {BACKGROUND AND OBJECTIVES: Alzheimer disease (AD) and dementia with Lewy bodies (DLB) often coexist, yet the cognitive effect of mixed AD and α-synuclein pathology in vivo remains unclear. We aimed to (1) characterize baseline neuropsychological profiles, (2) assess plasma biomarker associations, and (3) examine longitudinal cognitive trajectories in patients with AD, DLB, and mixed pathology in a memory clinic cohort.

METHODS: This was a retrospective longitudinal study including participants from an academic memory clinic cohort with available CSF and blood samples at baseline who completed a comprehensive cognitive assessment. Baseline neuropsychological performance was compared between groups using analysis of covariance controlling for age, sex, and education. Associations between plasma biomarkers and cognition were examined using multiple linear regression models. Linear mixed-effects models examined longitudinal change across groups, with time from baseline, diagnosis, the diagnosis-by-time interaction, baseline age, sex, and years of education as fixed effects, and intercept as a random effect.

RESULTS: A total of 350 participants (mean age 70.1 ± 6.6 years; 48.6% female) were included: AD alone (n = 249), AD with α-synuclein pathology (n = 31), DLB alone (n = 33), and DLB with AD pathology (n = 37). At baseline, patients with AD showed greater impairment than those with DLB in memory and language (all p < 0.01). Compared with AD alone, patients with AD and α-synuclein pathology showed poorer performance in visual attention/processing speed (F[1,259] = 7.71, p < 0.01) and ideomotor apraxia (F[1,244] = 4.02, p < 0.05). Conversely, patients with DLB and AD pathology performed worse than those with isolated DLB in visual memory (F[1,38] = 5.38, p < 0.05), constructional praxis (F[1,59] = 6.26, p < 0.01), and executive function (F[1,40] = 5.68, p < 0.05). Memory (p < 0.01) and language (p < 0.05) best differentiated groups with mixed pathology. Plasma phosphorylated tau at threonine 217 was broadly associated with worse performance across cognitive domains in patients with AD (p < 0.05). Longitudinally, patients with AD showed steeper decline than those with DLB in memory (β = 0.184, SE = 0.069, p < 0.01) and language (β = 0.206, SE = 0.074, p < 0.01). Within AD, those with α-synuclein pathology exhibited steeper decline in encoding (β = -0.186, SE = 0.075, p < 0.05) and delayed total recall (β = -0.178, SE = 0.082, p < 0.05). Among mixed-pathology patients, those with primary AD diagnosis showed greater decline across memory (β = -0.324, SE = 0.104, p < 0.01), language (β = -0.359, SE = 0.109, p < 0.01), and visuospatial function (β = -0.356, SE = 0.175, p < 0.05).

DISCUSSION: Distinct neuropsychological profiles and trajectories emerge in AD and DLB depending on underlying pathology. Identifying mixed pathology in vivo is clinically relevant for accurate diagnosis and prognosis and has implications for outcome measures and patient stratification in clinical trials.},
}

Humans
Female
*Alzheimer Disease/psychology/blood/complications
*Lewy Body Disease/psychology/blood/complications
Male
Aged
Neuropsychological Tests
Biomarkers/blood/cerebrospinal fluid
Longitudinal Studies
Retrospective Studies
alpha-Synuclein/cerebrospinal fluid
*Cognition
tau Proteins/blood/cerebrospinal fluid
Amyloid beta-Peptides/cerebrospinal fluid/blood
Aged, 80 and over

@article {pmid42385113,
year = {2026},
author = {Ting, SKS and Saffari, SE and Zhan, SJ and Gosavi, TD and Hameed, S and Li, W and Mukesh Shah, J and Lin, SZZ and Sim, J and Chiew, HJ and Ng, KP and Ng, ASL},
title = {Neuropathologic Correlates of Seizures in Patients With Alzheimer Disease and Dementia With Lewy Bodies.},
journal = {Neurology},
volume = {107},
number = {2},
pages = {e218277},
doi = {10.1212/WNL.0000000000218277},
pmid = {42385113},
issn = {1526-632X},
mesh = {Humans ; Female ; Male ; *Lewy Body Disease/pathology/complications/epidemiology ; *Alzheimer Disease/pathology/complications/epidemiology ; *Seizures/pathology/epidemiology ; Retrospective Studies ; Aged ; Aged, 80 and over ; *Brain/pathology ; Cohort Studies ; Cerebral Amyloid Angiopathy/pathology ; },
abstract = {BACKGROUND AND OBJECTIVES: Seizures are a recognized comorbidity in dementia, with varying prevalence across Alzheimer disease (AD) and dementia with Lewy bodies (DLBs). Although previous studies have demonstrated an increased seizure risk in AD, the neuropathologic substrates underlying seizure susceptibility-particularly across dementia subtypes-remain incompletely understood. We aimed to identify distinct clinicopathologic correlates of clinically active seizures in AD and DLB using a large autopsy-confirmed cohort.

METHODS: We conducted a retrospective cohort study using data from the National Alzheimer's Coordinating Center (2005-December 2022). Autopsy-confirmed AD and DLB cases were included. Individuals with a history of stroke or traumatic brain injury were excluded. The primary outcome was clinically active seizures, defined as seizures occurring within 3 years before or after the diagnosis of dementia. Neuropathologic exposures included Braak stage, cerebral amyloid angiopathy (CAA), frontotemporal lobar degeneration, and vascular pathologies. Multivariable logistic regression models were used to examine associations between pathologic features and seizure occurrence, adjusting for relevant demographic covariates.

RESULTS: A total of 3,498 participants were included, comprising 3,040 with AD (mean age, 73.4 years; 48.5% female) and 458 with DLB (mean age, 75.1 years; 31.4% female). Active seizures were identified in 174 participants with AD (5.7%) and 13 with DLB (2.8%). In AD, Braak stage VI (vs V) was associated with higher odds of active seizures (adjusted odds ratio [OR], 1.81; 95% CI 1.20-2.82; p = 0.007), as was moderate to severe CAA (adjusted OR, 1.38; 95% CI 1.01-1.90; p = 0.045). In DLB, AD-related pathologic features were not associated with seizures. By contrast, vascular pathology was significantly associated with seizure occurrence, including microinfarcts (adjusted OR, 5.11; 95% CI 1.64-16.4; p = 0.005) and infarcts (adjusted OR, 4.11; 95% CI 1.27-12.9; p = 0.015).

DISCUSSION: In this autopsy-confirmed cohort, seizure susceptibility was associated with advanced tau pathology and CAA in AD. In DLB, exploratory analyses suggested a possible association between vascular pathology and seizures; however, these findings should be interpreted cautiously. Overall, the results support potentially distinct pathologic contributions to seizure susceptibility across dementia subtypes. Limitations include the use of advanced-stage pathologic samples, which may limit generalizability to earlier disease stages.},
}

Humans
Female
Male
*Lewy Body Disease/pathology/complications/epidemiology
*Alzheimer Disease/pathology/complications/epidemiology
*Seizures/pathology/epidemiology
Retrospective Studies
Aged
Aged, 80 and over
*Brain/pathology
Cohort Studies
Cerebral Amyloid Angiopathy/pathology

@article {pmid42385118,
year = {2026},
author = {Morrill, VN and Pike, JR and Hu, J and Fornage, M and Surapaneni, A and Walker, KA and Knopman, DS and Mosley, TH and Coresh, J and Schneider, ALC and Smith, JR and Gottesman, RF},
title = {Genetic Risk for Alzheimer Disease, Midlife Hypertension, and Dementia: The ARIC Neurocognitive Study.},
journal = {Neurology},
volume = {107},
number = {2},
pages = {e218280},
doi = {10.1212/WNL.0000000000218280},
pmid = {42385118},
issn = {1526-632X},
mesh = {Humans ; *Hypertension/genetics/epidemiology ; Female ; *Alzheimer Disease/genetics/epidemiology ; *Dementia/genetics/epidemiology ; Male ; Middle Aged ; Genetic Risk Score ; *Genetic Predisposition to Disease ; Risk Factors ; Prospective Studies ; White People/genetics ; Black or African American/genetics ; United States/epidemiology ; Incidence ; },
abstract = {BACKGROUND AND OBJECTIVES: Genetics represent a nonmodifiable risk factor for Alzheimer disease (AD), with 60%-80% heritability. Midlife hypertension is a modifiable risk factor for both dementia and death. Our primary objective was to determine how genetic risk for AD modifies the association between hypertension and dementia.

METHODS: The Atherosclerosis Risk in Communities Study is an ongoing community-based prospective cohort study of 4 US centers. We analyzed White and Black participants free of dementia at age 55 years with genotypes and blood pressure measured at visit 1 (1987-1989). Three genetic risk groups (low, medium, high) were defined based on tertiles of a race-specific AD polygenic risk score. Dementia was ascertained through cognitive testing, informant interviews, hospitalization, codes and death records. Death was ascertained through the National Death Index. We examined the association of midlife hypertension with incident dementia within 3 genetic risk groups using Cox proportional-hazards and cumulative incidence function estimations. We used age 55 years as the time origin, with left truncation to allow entry at ages older than 55 years; age on December 31, 2022, was the administrative censoring date.

RESULTS: Among 8,931 White and 2,666 Black participants, the median follow up time was 26.6 and 23.8 years, the mean age was 54.0/53.5 years, and 53.0%/62.5% were female, respectively. After adjusting for demographics, midlife hypertension was significantly associated with dementia incidence across all genetic risk groups among White participants (low risk hazard ratio [HR] 1.29; 95% CI 1.07-1.55, medium risk HR 1.34; 95% CI 1.13-1.58, high risk HR 1.19; 95% CI 1.03-1.38) and among Black participants at high genetic risk (HR 1.31; 95% CI 1.04-1.66). Associations for low and medium genetic risk Black participants were consistent but not statistically significant. There were no significant differences in association of hypertension with dementia by AD genetic risk group. Individuals with hypertension had a 0%-2% higher probability of developing dementia by age 80 and a 6%-13% lower probability of dementia-free survival to age 80 years vs those without hypertension, across race and genetic risk groups.

DISCUSSION: Genetic risk for AD does not modify the association between hypertension and dementia. These data support the fact that all individuals with hypertension are likely to benefit from antihypertensive treatment.},
}

Humans
*Hypertension/genetics/epidemiology
Female
*Alzheimer Disease/genetics/epidemiology
*Dementia/genetics/epidemiology
Male
Middle Aged
Genetic Risk Score
*Genetic Predisposition to Disease
Risk Factors
Prospective Studies
White People/genetics
Black or African American/genetics
United States/epidemiology
Incidence

@article {pmid42385334,
year = {2026},
author = {Kim, W and Hwang, Y and Yang, Y and Kim, MG and Jang, H and Choi, SH and Seong, JK and Yoo, RE and Lee, WJ},
title = {Distinct spatial patterns of perivascular spaces enlargement for multiple and Co-existing pathologies of cognitive impairment.},
journal = {The journal of prevention of Alzheimer's disease},
volume = {13},
number = {8},
pages = {100631},
doi = {10.1016/j.tjpad.2026.100631},
pmid = {42385334},
issn = {2426-0266},
abstract = {BACKGROUND: This study examines how amyloid-β and vascular pathology independently and jointly relate to regional perivascular space (PVS) burden on T2-weighted MRI.

METHODS: In 307 cognitively impaired participants retrospectively identified from the Seoul National University dementia cohort, PVS were automatically quantified in the basal ganglia (BG) and lobar white matter regions from 2D T2-weighted MRI. Amyloid-β and vascular pathology positivity were defined by [18F]Florbetaben PET and small vessel disease markers. Group differences among pathology-negative (n=36), vascular-only (n=106), amyloid-only (n=48), and mixed (n=117) subgroups, as well as amyloid-vascular interactions, were assessed using analysis of covariance and multivariable linear regression.

RESULTS: BG PVS were greater in participants with vascular burden than in pathology-negative participants (F=26.97, p<0.001; Cohen's d=1.28), independent of amyloid-β. Lobar PVS were higher in single-pathology than pathology-negative participants across the parietal, temporal, and occipital regions (F=8.25-18.04, Cohen's d=0.66-0.98, all p≤0.014), with no additional increase in the mixed group. Greater amyloid-β retention was associated with parietal, temporal, and occipital PVS in VB- participants (β [95% CI]=0.55 [0.19, 0.92], 0.69 [0.35, 1.02], 0.40 [0.16, 0.64], respectively). Among AB- participants, vascular burden was associated with BG PVS (β [95% CI]=0.65 [0.40, 0.89]). Multivariable regression demonstrated less-than-additive AB×VB interactions in parietal, temporal, and occipital PVS (β [95% CI]=-0.65 [-1.08, -0.23], -0.74 [-1.13, -0.35], -0.42 [-0.70, -0.14], respectively).

CONCLUSIONS: Distinct regional PVS patterns reflect spatially selective and severity-dependent glymphatic-related structural alterations associated with amyloid-β and vascular pathologies, supporting PVS as a quantitative imaging biomarker for disentangling mixed pathways of cognitive impairment.},
}

@article {pmid42385487,
year = {2026},
author = {Oh, MJ and Lee, J and Jose, J and Bong, JH and Park, M},
title = {Construction of a bio-mimetic outer membrane layer via autodisplay of scFv onE. colifor SPR-based amyloid-β detection.},
journal = {Colloids and surfaces. B, Biointerfaces},
volume = {267},
number = {},
pages = {115947},
doi = {10.1016/j.colsurfb.2026.115947},
pmid = {42385487},
issn = {1873-4367},
abstract = {The development of highly sensitive biointerfaces is essential for the early diagnosis of Alzheimer's disease, characterized by the accumulation of amyloid-β(Aβ). In this study, a functionalized outer membrane layer using an scFv autodisplay system was constructed to enhance the performance of Surface Plasmon Resonance (SPR) biosensors. The single-chain variable fragment (scFv) against Aβ was genetically fused to an autotransporter and successfully expressed on the Escherichia coli outer membrane (OM). The biological activity and orientation of the autodisplayed scFv were validated via flow cytometry and fluorescence microscopy, showing a 35-fold higher binding affinity to Aβ compared to non-engineered controls. For the construction of the biointerface, isolated OM fractions were immobilized onto a gold substrate, forming a stable OM layer as confirmed by FT-IR spectroscopy. SPR analysis demonstrated that the scFv autodisplaying OM layer exhibited superior sensitivity with a limit of detection below 0.1 μg/mL and highly specific, concentration-dependent binding to Aβ. Crucially, the inherent physicochemical properties of the OM layer effectively minimized non-specific interactions, eliminating the need for additional blocking agents and ensuring structural stability even after washing steps. These findings establish the scFv autodisplay on an OM layer as a robust, scalable, and orientation-controlled platform for the label-free detection of biomarkers in complex biointerfaces.},
}

@article {pmid42385569,
year = {2026},
author = {Arruda Maciel, C and Oliveira da Silva, KG and Galbim de Paula, V and Alves Santana, V and Teles de Menezes, MCJ and Campos Gomes Pinto, F},
title = {Clinical response after cerebrospinal fluid shunting in complex versus pure idiopathic normal pressure hydrocephalus: A systematic review and meta-analysis.},
journal = {Clinical neurology and neurosurgery},
volume = {269},
number = {},
pages = {109557},
doi = {10.1016/j.clineuro.2026.109557},
pmid = {42385569},
issn = {1872-6968},
abstract = {BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) frequently coexists with neurodegenerative or vascular disease, but shunt outcomes in these complex presentations remain poorly synthesized.

METHODS: We performed a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 systematic review and meta-analysis of shunt outcomes in pure iNPH and complex iNPH. Binary outcomes were global shunt response and urinary improvement. Continuous outcomes were harmonized into cognition, gait, general function, and incontinence and summarized as standardized mean change with raw-score standardization (SMCR). Prespecified primary comparative estimates used random-effects models with Hartung-Knapp confidence intervals (CIs).

RESULTS: Nineteen unique analytical studies were included. In direct head-to-head binary comparisons, global shunt response was directionally lower in complex iNPH but did not reach statistical significance under the prespecified random-effects Hartung-Knapp model (odds ratio [OR] 0.31, 95% CI 0.09-1.10; k = 3). Urinary improvement did not clearly differ between phenotypes (OR 0.85, 95% CI 0.58-1.25; k = 3). Within complex iNPH, continuous pre-post estimates varied by domain and were imprecise: cognition was directionally positive, gait was near null with marked heterogeneity, and incontinence showed a small positive estimate. Direct continuous complex-minus-pure comparisons did not show a consistent deficit across domains. Exploratory time meta-regression suggested a phenotype-by-time interaction for incontinence, but this signal was based on sparse follow-up support and should be considered hypothesis-generating.

CONCLUSIONS: Low- to very-low-certainty evidence suggests that complex iNPH is associated with greater uncertainty and possibly lower global response than pure iNPH, but lower odds of response should not be interpreted as absence of response. Counseling should be phenotype-aware and domain-specific, particularly when Alzheimer-related biomarkers, parkinsonism, vascular burden, or other neurodegenerative features coexist with suspected iNPH.},
}

@article {pmid42385584,
year = {2026},
author = {Kiprov, DD and Green, AP and Boyinapalli, P},
title = {Technological advances in selective plasma adsorption: The MTx.100 column and the emergence of subtractive precision medicine.},
journal = {Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis},
volume = {65},
number = {4},
pages = {104484},
doi = {10.1016/j.transci.2026.104484},
pmid = {42385584},
issn = {1473-0502},
abstract = {Therapeutic plasma exchange (TPE) is well-established for autoimmune, hematological, and neurological disease but is intrinsically non-selective: protective immunoglobulins, coagulation factors, and albumin are depleted alongside pathogenic substances, and reliance on donor-derived replacement fluid carries logistical and immunological costs. The MTx.100 column (Marker Therapeutics AG) is a selective plasma adsorption device that addresses these limitations through hydrophobic-affinity adsorption. It targets pro-inflammatory cytokines, protein-bound metabolic waste, hydrophobic environmental contaminants, and microparticulates while preserving immunoglobulins, coagulation factors, electrolytes, and the patient's own signaling proteins. Plasma is treated and conserved, eliminating replacement-fluid dependency. Clinical experience encompasses approximately 1000 procedures globally. A prospective single-arm multicenter trial in 107 critically ill COVID-19 patients (424 procedures) demonstrated 28-day mortality of 37.4% against an FDA-agreed performance goal of 88.1% (p < 0.0001); propensity-matched analysis showed approximately three-fold higher survival odds versus standard of care (OR 3.0; 95% CI 1.56-5.85; p = 0.0008), with significant reductions in inflammatory and metabolic markers and no serious adverse events attributable to the column or procedure. Hospital case reports across polytrauma, post-LVAD implantation, and toxin-induced hepatitis demonstrated hemodynamic and electrolyte stability and favorable clinical trajectories. Across 114 elective outpatient procedures, vital signs and electrolytes remained stable throughout treatment, and third-party laboratory analyses confirmed measurable reduction of PFAS, microplastics, and persistent organic pollutants in treated patients. Within the emerging framework of subtractive precision medicine, selective plasma adsorption offers a complementary paradigm to additive pharmacotherapy for conditions characterized by inflammatory and toxic burden. A pilot trial in Alzheimer's disease is underway.},
}

@article {pmid42385586,
year = {2026},
author = {Khatri, BO},
title = {Therapeutic plasma exchange in Alzheimer's disease: From clinical trial to real-world evidence.},
journal = {Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis},
volume = {65},
number = {4},
pages = {104481},
doi = {10.1016/j.transci.2026.104481},
pmid = {42385586},
issn = {1473-0502},
abstract = {This article examines the expanding role of therapeutic plasma exchange (TPE) in Alzheimer's disease (AD), alongside recent developments in diagnostic approaches, disease mechanisms, and emerging disease-modifying treatments. Although AD has historically been considered a disorder defined by amyloid and tau pathology, contemporary models increasingly emphasize a multifactorial systems-biology framework that includes immune dysregulation, oxidative stress, vascular injury, impaired protein clearance, and synaptic dysfunction. Within this evolving model, TPE has emerged as a biologically rational, broadly acting therapeutic strategy that contrasts mechanistically with selective anti-amyloid monoclonal antibodies. This article reviews the global burden of AD and the need for safer disease-modifying therapies; current understanding of AD pathophysiology and biomarker-based diagnosis; available symptomatic and disease-modifying treatments; the AMBAR trial and the earlier pilot work that supported it; real-world cohort evidence; the author's clinical experience with TPE in AD; the mechanism of action of TPE in comparison with anti-amyloid monoclonal antibodies; the evolution of TPE from acute hospital-based therapy to chronic outpatient disease management; and future directions for TPE in neurodegenerative disease.},
}

@article {pmid42385644,
year = {2026},
author = {Luo, J and Rasmussen, IJ and Thomassen, JQ and Frikke-Schmidt, R},
title = {Causal insights of modifiable cardiovascular risk factors for dementia risk - potential for efficient prevention and improved brain health.},
journal = {Atherosclerosis},
volume = {419},
number = {},
pages = {120824},
doi = {10.1016/j.atherosclerosis.2026.120824},
pmid = {42385644},
issn = {1879-1484},
abstract = {BACKGROUND: The 2024 Lancet Commission report identifies 14 modifiable risk factors that may prevent half of dementia. The causal nature of these associations remains however unclear. We aimed to establish robust causal estimates for modifiable cardiovascular risk factors and dementia, offering tangible targets for effective dementia prevention.

METHODS: We selected independent variants from the largest genomic consortia to date (N = 439,214 to 3,037,499) for each modifiable risk factor and generated polygenic risk scores for participants of European ancestry in the UK Biobank (N = 408,788). We conducted univariable and multivariable linear Mendelian randomization, assessed genetic shapes by nonlinear approaches, and performed several sensitivity analyses, including sex stratification.

RESULTS: Genetic predisposition to high low-density-lipoprotein cholesterol (LDL-C) (1.12, 1.01-1.23), non-high-density-lipoprotein cholesterol (1.30, 1.26-1.35), triglycerides (1.19, 1.01-1.41), body mass index (1.04, 1.02-1.07), systolic (1.14, 1.09-1.20) and diastolic (1.10, 1.02-1.19) blood pressure, type 2 diabetes (1.04, 1.00-1.09) and smoking (1.18, 1.06-1.32), were associated with increased risk of all-cause dementia, while longer education was associated with a reduced risk (0.58, 0.33-0.99). Results for Alzheimer's disease and vascular dementia were directionally similar. Moreover, genetically predicted high physical activity level was associated with low risk of Alzheimer's disease (0.58, 0.33-0.99) only. Sensitivity analyses supported the main results, and no nonlinear shapes were detected.

CONCLUSION: These findings provide causal insights into modifiable cardiovascular risk factors for dementia and unfold a substantial potential for dementia prevention by timely treatment of high LDL-C, triglycerides, hypertension, and diabetes, alongside smoking cessation and maintenance of normal weight.},
}

@article {pmid42385702,
year = {2026},
author = {Zhou, Z and Luquette, LJ and Dong, G and Kim, J and Ku, J and Kim, K and Ramesh, N and Bae, M and Caplin, A and Shao, DD and Sahile, B and Essuman, K and Goodman, E and Miller, MB and Huang, AY and Nathan, WJ and Nussenzweig, A and Park, PJ and Lagier-Tourenne, C and Lee, EA and Walsh, CA},
title = {Recurrent patterns of TOP1-mediated neuronal genomic damage shared by major neurodegenerative disorders.},
journal = {Cell},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cell.2026.06.013},
pmid = {42385702},
issn = {1097-4172},
abstract = {Amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer's disease (AD) represent two major categories of neurodegenerative disorders-TAR DNA-binding protein 43 (TDP-43) and tau proteinopathies-for which the mechanisms driving neuronal death remain unclear. Single-cell whole-genome sequencing of 469 neurons from C9ORF72 ALS, C9ORF72 FTD, AD, and control brains revealed increased somatic single-nucleotide variants (sSNVs) and insertions/deletions (sIndels) in all three diseases. Mutational signature analysis identified a disease-associated sSNV signature consistent with oxidative damage and an sIndel process affecting 22% of ALS, 76% of FTD, and 61% of AD neurons-but only 2% of control neurons-resembling signature ID4, previously linked to topoisomerase 1 (TOP1)-mediated mutagenesis. Rapid approach to DNA adduct recovery (RADAR) assays confirmed increased TOP1-DNA covalent complexes, and duplex sequencing confirmed the increased sIndels and identified single-strand events as likely precursor lesions. TOP1-associated sIndel mutagenesis and genome instability thus represent a mechanism shared by both TDP-43 and tau neurodegeneration.},
}

@article {pmid42385975,
year = {2026},
author = {Abhishek, and Singh, S},
title = {ARBUTIN AS A THERAPEUTIC CANDIDATE FOR AUTISM: CURRENT EVIDENCE AND MECHANISTIC INSIGHTS INTO PI3K/Akt/mTOR and Nrf2 PATHWAYS.},
journal = {European journal of pharmacology},
volume = {},
number = {},
pages = {179103},
doi = {10.1016/j.ejphar.2026.179103},
pmid = {42385975},
issn = {1879-0712},
abstract = {Arbutin is a natural glycoside that protects neurons and is useful in a variety of neurological conditions. There is a need to further explore its scientific properties as arbutin regulates mitochondrial function, control apoptotic proteins, lowers oxidative stress, enhance behavioral and cognitive outcomes and thus may be considered a potential target for Parkinson's, Alzheimer's, neuroinflammation, epilepsy and Huntington's disease. Arbutin via PI3K/Akt/mTOR and Nrf2 signaling pathways, helps to balance redox equilibrium, mitochondrial integrity and neuronal survival, plays a major role in mediating these effects. Autism Spectrum Disorder (ASD) is closely associated with dysfunction of these pathways, which cause oxidative2 stress, synaptic deficits and neuroinflammation. While reducing NF-κB mediated pro-inflammatory cytokines including TNF-α, IL-1β and IL-6, arbutin increases Akt phosphorylation and Nrf2 nuclear translocation, activating antioxidant enzymes like SOD, GSH, HO-1 and NQO1. These coordinated molecular processes may help preserve neuronal homeostasis, inhibit apoptosis and decrease ROS induced neuronal damage. Arbutin may enhance synaptic plasticity and potentially modulate the pathogenic pathways underlying ASD and other neurodevelopmental disorders by concurrently regulating oxidative stress, mitochondrial dysfunction and neuroinflammation. Taken together these finding suggest arbutin may act as a promising therapeutic candidate capable of restoring neuronal homeostasis and translating mechanistic understanding into potential therapeutic applications. Arbutin is a promising phytochemical with potential relevance for autism and associated neurological diseases due to its combined molecular actions. However, direct experiment and clinical evidence supporting the role of arbutin in ASD remains limited.},
}

@article {pmid42372237,
year = {2026},
author = {Marschner, RA and da Silva, FM and Crispim, D and Saraiva Gonçalves, CA},
title = {Muscle-Brain Crosstalk in Alzheimer's Disease: Exercise-Associated FNDC5/Irisin Pathways in Preclinical Models - A Systematic Review.},
journal = {Aging and disease},
volume = {},
number = {},
pages = {},
doi = {10.14336/AD.2026.0427},
pmid = {42372237},
issn = {2152-5250},
abstract = {Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive decline, synaptic dysfunction, neuroinflammation, and altered amyloid-β processing. Growing evidence suggests that physical exercise exerts neuroprotective effects partly mediated by myokines released from skeletal muscle. Among these, irisin, a cleavage product of fibronectin type III domain-containing protein 5 (FNDC5), has emerged as a potential component of muscle-brain communication involved in neuroplasticity and memory-related pathways. This systematic review summarizes evidence from preclinical in vivo studies investigating exercise-induced FNDC5 expression and irisin-related signaling pathways in experimental models of AD. A literature search was conducted in PubMed and EMBASE following PRISMA guidelines to identify studies evaluating the effects of physical exercise on FNDC5 expression, irisin-related pathways, and cognitive outcomes in animal models of AD. Ten preclinical studies met the inclusion criteria and were included in the qualitative synthesis, encompassing both behavioral and mechanistic evidence. Overall, the evidence indicates that physical exercise was associated with increased FNDC5 expression, activation of irisin-related pathways, and downstream neuroprotective mechanisms including PPARGC1A, AMPK, SIRT1, and BDNF signaling. These molecular adaptations were associated with improvements in synaptic plasticity, reductions in neuroinflammation and oxidative stress, and attenuation of amyloid-related pathology. Behavioral assessments across multiple paradigms also demonstrated improvements in learning and memory following exercise interventions. Collectively, the available preclinical evidence suggests that FNDC5/irisin-related signaling is associated with neuroprotective effects of physical exercise in experimental models of AD as part of a broader exercise-induced response. Further studies are needed to clarify the underlying mechanisms and translational relevance of this pathway in AD.},
}

@article {pmid42372338,
year = {2026},
author = {Ersözlü, E and Preis, L and Aktuz, A and Droste, L and Erman, A and Gref, D and Strentz, KS and Hellmann-Regen, J and , },
title = {Drawing a line: Differentiating mild from moderate dementia using the functional activities questionnaire.},
journal = {The journal of prevention of Alzheimer's disease},
volume = {13},
number = {8},
pages = {100630},
doi = {10.1016/j.tjpad.2026.100630},
pmid = {42372338},
issn = {2426-0266},
abstract = {BACKGROUND: Accurate differentiation between mild and moderate dementia is increasingly important, particularly as amyloid-targeting therapies are restricted to early disease stages. Functional impairment in instrumental activities of daily living is a hallmark of progression beyond mild dementia. The informant-based Functional Activities Questionnaire (FAQ) is widely used, but empirically validated cut-offs distinguishing mild from moderate dementia remain insufficiently defined.

METHODS: The optimal cut-off score was derived from the entire National Alzheimer's Coordinating Center (NACC) Uniform Data Set as a discovery cohort (n = 34,513) and validated in two independent multicentric cohorts (Alzheimer's Disease Neuroimaging Initiative (ADNI) n = 381 and Frontotemporal Lobar Degeneration Neuroimaging Initiative (FTLDNI) n = 74). The dementia staging was based on the Clinical Dementia Rating (CDR) global score. Functional impairment was assessed using the 10-item FAQ. Receiver operating characteristic analyses in NACC identified optimal thresholds, which were applied unchanged in validation cohorts. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated, and discordant cases were examined to identify factors associated with misclassification.

RESULTS: In NACC, the FAQ demonstrated excellent discrimination of moderate dementia (AUC=0.947, 95% CI 0.944-0.949). A cut-off value of ≥18 maximized discrimination (sensitivity 96%, specificity 87%). A higher threshold of ≥23 improved specificity (92%), while maintaining sensitivity (83%). In ADNI and FTLDNI, the sensitivity of ≥18 threshold yielded 92% and 94%, respectively. Moreover, older age and lower cognitive performance were associated with higher odds of misclassification.

CONCLUSIONS: The FAQ robustly differentiates mild from moderate dementia across diverse cohorts. A threshold of ≥18 prioritizes sensitivity, whereas ≥23 favors specificity, supporting context-dependent functional staging in clinical and research settings. Individuals with FAQ scores between 18 and 22 may benefit from more detailed clinical staging.},
}

@article {pmid42372723,
year = {2026},
author = {Tyagi, M and de Hoog, E and Grega, M and Sullivan, KR and Walker, AC and Chadha, R and Northrop, A and Fábián, B and Hummer, G and Fuxreiter, M and Hyman, BT and Shepherd, JD},
title = {Arc mediates intercellular tau transmission via extracellular vesicles.},
journal = {Cell},
volume = {},
number = {},
pages = {},
pmid = {42372723},
issn = {1097-4172},
abstract = {Tau pathology spreads cell to cell, but the mechanisms of intercellular tau transmission remain unclear. We find that the neuronal gene Arc is critical for the release of tau in neuronal extracellular vesicles (EVs) via a direct protein-protein interaction. Brain EVs purified from transgenic rTg4510 mutant tau mice (rTg[WT]) crossed with Arc knockout mice (rTg[Arc KO]) contain less tau and reduced tau seeding potential. Both Arc and tau are co-packaged in mouse and human brain-derived EVs. Moreover, Arc levels in brain-derived EVs isolated from human Alzheimer's disease (AD) brains show a strong positive correlation with phosphorylated EV-tau levels. rTg[Arc KO] mice have increased accumulation of intracellular tau and a modest increase in cell toxicity early in disease progression. Strikingly, intercellular tau transmission is almost absent in Arc KO mice. These results show that Arc is critical for the packaging of tau in EVs, which plays a significant role in intercellular tau transmission.},
}

@article {pmid42372923,
year = {2026},
author = {Lin, Z and Hu, L and Liu, Y and Ning, W and Wang, S and Fu, ZY and Guan, L},
title = {Rational design, synthesis, and biological evaluation of chalcone hybrids including benzoylpiperazin (phenylacetylpiperazin)-thiophene as anti- Alzheimer's agents.},
journal = {Bioorganic & medicinal chemistry letters},
volume = {},
number = {},
pages = {130716},
doi = {10.1016/j.bmcl.2026.130716},
pmid = {42372923},
issn = {1464-3405},
abstract = {A series of chalcone hybrids including benzoylpiperazin (phenylacetylpiperazin)-thiophene were designed, synthesized and evaluated their inhibitory activities against cholinesterase (ChE). All compounds displayed good inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Among them, compound 2e displayed the most inhibitory activity against AChE, BChE and β-amyloid (Aβ42) with IC50 values 7.01, 5.39 and 4.47 μM, respectively. Meanwhile, 2e was found anti-Alzheimer's disease (AD) effect by significantly alleviating lipopolysaccharide (LPS)/Aβ-induced neurotoxicity, reducing the levels of reactive oxygen species (ROS), pro-inflammatory cytokines, and exert anti-inflammatory effects by regulating the NF-κB (Nuclear factor kappa-light-chain-enhancer of activated B cells) pathway. Furthermore, the molecular modeling studies showed that 2e target both catalytic active site as well as peripheral anionic site of AChE, BChE and Aβ42, and possess strong bind affinity. In addition, in silico ADMET and toxicity predictions demonstrated favorable oral absorption and potential blood-brain barrier (BBB) permeability for 2e. The rationale remains partly overstated. The novelty claim should more precisely distinguish this scaffold from previously reported chalcone, piperazine, thiophene, and multitarget ChE/Aβ inhibitors. The phrase "anti-Alzheimer's agents" should be softened, because the data are limited to enzyme assays, Aβ assays, BV-2 cellular models, docking, and computational predictions.},
}

@article {pmid42372976,
year = {2026},
author = {Price, TM and Tucker, AE and Funk, KE},
title = {Molecular and Environmental Drivers of Tau Post-Translational Modifications and Tau Pathology.},
journal = {Ageing research reviews},
volume = {},
number = {},
pages = {103223},
doi = {10.1016/j.arr.2026.103223},
pmid = {42372976},
issn = {1872-9649},
abstract = {Tau is an intrinsically disordered protein that functions to support cytoskeletal stability by binding microtubules in neuronal axons. While tau is involved in healthy neuronal function, it can become pathogenic by forming protein aggregates leading to neurologic diseases collectively known as tauopathies, which include Alzheimer's disease, frontotemporal dementia, and chronic traumatic encephalopathy. Post-translational modifications, including phosphorylation, O-GlcNAcylation, acetylation, methylation, ubiquitination, and protein truncation are molecular drivers that promote tau aggregation and subsequent disease development. There is a growing, but incomplete, understanding of the complex crosstalk that occurs among distinct modifications and how they orchestrate tau pathogenesis in concert. The drivers of tau post-translational modifications are not fully understood, but environmental factors, such as traumatic brain injuries, microbial infections, alcohol abuse, chronic stress, and heavy metal pollutants, increase risk of tau pathology formation. In this article we review the current literature describing the molecular changes that increase tau aggregation propensity, the environmental factors that promote those changes, and the multifactorial crosstalk that modulates tau pathogenesis. Our goal is to outline the biological pathways and molecular factors that drive tau pathogenesis in order to identify potential points of behavioral and/or therapeutic intervention for tauopathies.},
}

@article {pmid42373039,
year = {2026},
author = {Gao, K and Bao, J and Song, Y and Lin, CP and Iturria-Medina, Y and Biswal, BB and Wang, P},
title = {Beyond gray matter: unveiling the critical role of white matter in Alzheimer's disease.},
journal = {Progress in neuro-psychopharmacology & biological psychiatry},
volume = {},
number = {},
pages = {111816},
doi = {10.1016/j.pnpbp.2026.111816},
pmid = {42373039},
issn = {1878-4216},
abstract = {Alzheimer's disease (AD) has traditionally been regarded as a disorder primarily affecting gray matter, while growing evidence highlights the significant role of white matter pathology in its progression. This review aims to assess the current state of knowledge regarding white matter abnormalities and elucidate the potential impact of white matter on the pathogenesis and progression of AD. White matter alterations, including inflammation, hyperintensities, structural and functional changes, often precede gray matter atrophy and cognitive decline during AD progression. Advanced imaging and histopathological studies suggest that white matter degeneration is not merely a downstream consequence of gray matter pathology; it may represent an independent, perhaps initiating, pathological pathway in AD progression. Moreover, white matter lesions in individuals with AD may be modifiable by both pharmacological and non-pharmacological interventions, supporting the potential for reducing white matter damage and improving cognitive functions.},
}

@article {pmid42373045,
year = {2026},
author = {Bulycheva, I and Watanabe, Y and Kitamura, K and Kabasawa, K and Saito, T and Takahashi, A and Kobayashi, R and Oshiki, R and Yamazaki, O and Watanabe, K and Takachi, R and Murai, U and Tsugane, S and Nakamura, K},
title = {Association between high dietary polyphenol intake and reduced risk of dementia: a 12-year cohort study.},
journal = {Clinical nutrition ESPEN},
volume = {},
number = {},
pages = {103438},
doi = {10.1016/j.clnesp.2026.103438},
pmid = {42373045},
issn = {2405-4577},
abstract = {BACKGROUND & AIMS: Dietary polyphenols may play a modifiable role in reducing the risk of dementia; however, current evidence remains limited and inconclusive. This study aimed to investigate whether dietary polyphenol intake, taking caffeine intake into account, is associated with dementia risk in middle-aged and older people.

METHODS: Participants of this 12-year cohort study were 13,473 community-dwelling individuals aged 40-74 years (51.9% female). Dietary intake data were collected from 2011 to 2013 using a validated food frequency questionnaire. Polyphenol intake was adjusted for energy intake using the residual method. The outcome was incident dementia determined using Japan's long-term care insurance database. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs). Covariates included demographic factors, body size, lifestyle habits, and disease history (myocardial infarction, stroke, diabetes mellitus). An additional multivariable analysis was conducted, further adjusting for energy-adjusted caffeine intake.

RESULTS: The mean age of participants was 59.1 years. During follow-up, 337 males and 331 females developed dementia. Higher polyphenol intake was associated with a lower risk of dementia (multivariable-adjusted P for trend <0.0001), with the highest quintile (Q5) having a reduced risk of dementia (HR = 0.62, 95%CI: 0.49-0.78) compared to the lowest quintile (Q1, reference). After further adjusting for energy-adjusted caffeine intake, this association remained significant (P for trend = 0.0149), with Q5 having an HR of 0.70 (95%CI: 0.52-0.95). In males, higher polyphenol intake was associated with a lower hazard of dementia (multivariable-adjusted P for trend = 0.0002), with Q4 and Q5 having a lower hazard (Q4: HR = 0.59, 95% CI: 0.42-0.83; Q5: HR = 0.55, 95%CI: 0.40-0.76) compared to Q1. In females, higher polyphenol intake was associated with a lower hazard of dementia (multivariable-adjusted P for trend = 0.0106), with Q5 having a lower hazard (HR = 0.68, 95%CI: 0.49-0.96) compared to Q1.

CONCLUSION: High polyphenol intake is robustly associated with a decreased risk of dementia in middle-aged and older individuals, with the association remaining even after accounting for caffeine intake.},
}

@article {pmid42373097,
year = {2026},
author = {Chen, X and Wang, Z and Wang, J and Kong, D and Wang, X and Lu, L and Nelson, PT and Zhou, FM and Liao, FF},
title = {Distinctly altered TRPC3 and TRPC6 expression patterns in human Alzheimer's disease cortex and hippocampus.},
journal = {Brain pathology (Zurich, Switzerland)},
volume = {},
number = {},
pages = {e70118},
doi = {10.1111/bpa.70118},
pmid = {42373097},
issn = {1750-3639},
support = {R01-NS120327/NH/NIH HHS/United States ; R01-AG072703/NH/NIH HHS/United States ; P01 AG078116/NH/NIH HHS/United States ; P30 AG072946/NH/NIH HHS/United States ; 2023Y9286//Joint Funds for the Innovation of Science and Technology, Fujian province, China/ ; 2024J011004//Fujian Provincial Natural Science Foundation/ ; //Fujian Research and Training Grants for Young and Middle-aged Leaders in Healthcare, China/ ; },
abstract = {Calcium dysregulation is increasingly recognized as a convergent mechanism underlying neuronal vulnerability and glial overactivation in Alzheimer's disease (AD). Transient Receptor Potential Canonical (TRPC) channels are potential key modulators of Ca[2+] signaling in multiple cell types in central nervous system (CNS), mediating different pathophysiological roles. However, their cell type-specific remodeling and cellular origins of these changes in human AD tissue remain poorly defined. This study investigated their expression patterns with main focus on the two closely related members of TRPC3 and TRPC6 across human AD brains and two relevant mouse models. Formalin-fixed paraffin-embedded cortical and hippocampal tissues from AD patients and age-matched controls were examined using immunohistochemistry. Spatial relationships between TRPC3/TRPC6 and glial fibrillary acidic protein (GFAP)-positive astrocytes were assessed in adjacent serial sections. TRPC3 expression was markedly increased in AD cortex and hippocampus whereas TRPC6 was significantly reduced primarily in pyramidal neurons. TRPC3-positive regions showed close spatial correspondence with reactive astrocytes, particularly in the hippocampal and subcortical white matter regions, suggesting a partial astrocytic origin. TRPC6 exhibited negligible overlap with GFAP. These observations were reproduced in brain sections of both 5xFAD and PS19 transgenic (Tg) mice compared to their littermate controls. Our findings reveal a conserved pattern of divergent TRPC remodeling across human and mouse models with AD pathology. In addition, TRPC1 expression was significantly reduced in AD samples while TRPC4 and TRPC5 had no significant change in expression. Taken together, selected TRPC family members may undergo differential remodeling during AD pathogenesis, with TRPC3 and TRPC6 showing the most prominent and consistent alterations.},
}

@article {pmid42373113,
year = {2026},
author = {Weiss, SM and Watt, JA and Ewa, V and Straus, SE},
title = {Lecanemab use for early Alzheimer disease in Canada.},
journal = {CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne},
volume = {198},
number = {25},
pages = {E973-E976},
doi = {10.1503/cmaj.260193},
pmid = {42373113},
issn = {1488-2329},
}

@article {pmid42373496,
year = {2026},
author = {Wang, AM and Wang, YX and Ma, YH and Yang, XY and Guo, GY and Song, WC and Wang, SZ and Shi, FY},
title = {[Study on the risk factors of development for mild cognitive impairment to Alzheimer's disease based on the competitive risk joint model].},
journal = {Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi},
volume = {47},
number = {6},
pages = {1158-1164},
doi = {10.3760/cma.j.cn112338-20251013-00718},
pmid = {42373496},
issn = {0254-6450},
support = {81803337, 81872719//National Natural Science Foundation of China/ ; ZR2023MH313//Natural Science Foundation of Shandong Province/ ; 2019-10-156//Shandong Provincial Higher Education Youth Talent Introduction and Cultivation Program/ ; },
mesh = {*Alzheimer Disease ; Humans ; *Cognitive Dysfunction ; Risk Factors ; Boosting Machine Learning Algorithms ; Disease Progression ; Random Forest ; Female ; },
abstract = {Objective: To identify the risk factors for the progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD) using a competing risks joint model. Methods: This study was based on the Alzheimer's Disease Neuroimaging Initiative database. Three gradient boosting tree algorithm, namely CatBoost, XGBoost, and LightGBM, were employed to reduce the dimensionality of the high-dimensional lipoprotein and metabolite data (including 250 amino acids, lipids, and energy metabolism-related components, etc.). A random survival forest model (RSF) was used to screen out key demographic, cognitive function scores and metabolic variables. A competing risk joint model was constructed to identify the risk factors for the progression from MCI to AD. Results: A total of 8 lipoprotein and metabolite variables were identified by the three algorithms [creatinine, lactate, glycine, large high-density lipoprotein phospholipids percent (L_HDL_PL_PCT), acetic acid, tyrosine, β-hydroxybutyric acid and valine]. The RSF model identified 14 main variables, including cognitive function indicators [Functional Activities Questionnaire (FAQ), Alzheimer's Disease Assessment Scale-13 items (ADAS13), Alzheimer's Disease Assessment Scale word recognition item 4 (ADASQ4), and Alzheimer's Disease Assessment Scale-11 items (ADAS11)], lipoprotein and metabolites (acetic acid, L_HDL_PL_PCT, β-hydroxybutyrate, glycine, and creatinine), and baseline characteristics [age, years of education, marital status, retirement status, and apolipoprotein E ε4 allele (APOE-ε4)]. The univariate competing risk joint model showed that the longitudinal changes of ADAS11, ADAS13, ADASQ4, FAQ, and glycine, as well as baseline age, marital status, and APOE-ε4, were positively associated with the progression of MCI to AD (P<0.05). The results of the multivariate competing risk joint model further indicated that the longitudinal changes of ADAS13, ADASQ4, FAQ, and glycine, as well as baseline age, marital status, and APOE-ε4 were positively associated with AD incidence (P<0.05). Conclusions: Longitudinal increases in ADAS13, ADASQ4, FAQ, and glycine, as well as older age, unfavorable marital status, and APOE-ε4 carriage at baseline, were all risk factors for progression from MCI to AD.},
}

*Alzheimer Disease
Humans
*Cognitive Dysfunction
Risk Factors
Boosting Machine Learning Algorithms
Disease Progression
Random Forest
Female

@article {pmid42373580,
year = {2026},
author = {Lee, J and Olafson, E and Toth, B and Casavant, E and Schauer, S and Bittner, T and Meyer, MR and Verghese, PB and Venkatesh, V and West, T and Braunstein, JB and Biever, A and Calderon, E and Mandl, M and Bayfield, A and Hoogenraad, CC and Teng, E and Monteiro, C and Anania, VG and Bohórquez, SMS and Yeh, FL},
title = {Evaluation of CSF and plasma tau species as fluid surrogate candidates for tau PET in prodromal to moderate Alzheimer's disease.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {7},
pages = {e71604},
pmid = {42373580},
issn = {1552-5279},
support = {//Genentech Inc/ ; },
mesh = {Humans ; *tau Proteins/cerebrospinal fluid/blood/metabolism ; *Alzheimer Disease/diagnostic imaging/cerebrospinal fluid/blood/metabolism ; *Positron-Emission Tomography ; Female ; Biomarkers/cerebrospinal fluid/blood ; Male ; Aged ; Prodromal Symptoms ; Middle Aged ; Phosphorylation ; },
abstract = {INTRODUCTION: Positron emission tomography (PET) is a valuable tool for assessing tau pathology in Alzheimer's disease (AD), but it is not widely accessible. Clarifying the relationship between fluid tau species and tau PET in AD may allow for the identification of fluid biomarkers that could serve as more accessible surrogates for tau PET.

METHODS: Cerebrospinal fluid (CSF) and plasma tau species levels were assessed across prodromal to moderate AD subjects (CSF: n = 53, plasma: n = 181) via immunoassays and liquid chromatography-mass spectrometry. Fluid measures were correlated with [[18]F]GTP1 tau PET at baseline for head-to-head comparisons across analytes.

RESULTS: CSF C2N-eMTBR-tau243, tau phosphorylated at threonine 205 (p-tau205), p-tau217, and a peptide from the tau-441 microtubule-binding region (MTBR) (MTBR/243-254) exhibited the highest correlations with [[18]F]GTP1 standardized uptake value ratio. Plasma p-tau181 and p-tau217 demonstrated correlation rankings with tau PET similar to those observed with corresponding CSF analytes.

DISCUSSION: CSF C2N-eMTBR-tau243, MTBR/243-254, p-tau205, and p-tau217 demonstrated comparable strong correlations with tau PET. These findings may guide future development of plasma biomarker surrogates for tau PET.},
}

Humans
*tau Proteins/cerebrospinal fluid/blood/metabolism
*Alzheimer Disease/diagnostic imaging/cerebrospinal fluid/blood/metabolism
*Positron-Emission Tomography
Female
Biomarkers/cerebrospinal fluid/blood
Male
Aged
Prodromal Symptoms
Middle Aged
Phosphorylation

@article {pmid42373784,
year = {2026},
author = {Li, Y and Ulrich, JD and Holtzman, DM},
title = {Adaptive immunity in the pathogenesis of neurodegeneration.},
journal = {Nature immunology},
volume = {27},
number = {7},
pages = {1375-1389},
pmid = {42373784},
issn = {1529-2916},
support = {AG085374//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; AG069701//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; AG078106//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; AG083977//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; NS090934//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; },
mesh = {Humans ; *Adaptive Immunity/immunology ; *Neurodegenerative Diseases/immunology/pathology/therapy ; Animals ; Microglia/immunology ; *Central Nervous System/immunology/pathology ; Astrocytes/immunology ; Immunity, Innate ; },
abstract = {Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and others, are a group of neurological disorders characterized by progressive neuronal loss in the central nervous system (CNS) and the deterioration of CNS function. Multiple lines of evidence have highlighted activation of innate immune cells in the CNS, namely microglia and astrocytes, as hallmark pathological features in neurodegeneration and key drivers of disease progression. Advances in genetic, neuropathological and experimental studies also underscore the potential role of the adaptive immune system in disease pathogenesis. Here we summarize the current understanding of how adaptive immunity can shape the progression of neurodegenerative diseases and highlight cross-disease parallels and potentially shared mechanisms. We also examine cellular events leading to the recruitment of peripheral immune cells to the CNS, as well as candidate antigens driving the adaptive immune response. Last, we discuss potential therapeutic strategies to treat neurodegeneration via the manipulation of adaptive immune cells.},
}

Humans
*Adaptive Immunity/immunology
*Neurodegenerative Diseases/immunology/pathology/therapy
Animals
Microglia/immunology
*Central Nervous System/immunology/pathology
Astrocytes/immunology
Immunity, Innate

@article {pmid42373786,
year = {2026},
author = {Guo, AX and Fisher, TM and Comandante-Lou, N and De Jager, PL and Liddelow, SA},
title = {Innate immune signaling and functions in astrocytes.},
journal = {Nature immunology},
volume = {27},
number = {7},
pages = {1364-1374},
pmid = {42373786},
issn = {1529-2916},
support = {AARF-24-1313800/ALZ/Alzheimer's Association/United States ; U01 AG061356/AG/NIA NIH HHS/United States ; },
mesh = {*Astrocytes/immunology/metabolism ; Humans ; *Immunity, Innate/immunology ; Animals ; *Signal Transduction/immunology ; Toll-Like Receptors/metabolism/immunology ; Innate Immunity Recognition ; Inflammasomes/metabolism/immunology ; },
abstract = {Astrocytes, long considered supportive cells of the central nervous system (CNS), have critical roles in innate immunity. This Review explores immune signaling pathways in astrocytes, including pattern recognition through Toll-like receptors, nucleic acid sensors and inflammasomes. These pathways enable the detection of danger signals and initiate protective responses and endogenous innate immune functions. Downstream signaling pathways, including the interferon, NF-κB and STAT3 pathways, mediate astrocyte reactivity and drive cytokine secretion, antiviral responses, phagocytosis and many other immune functions. While these responses are crucial for CNS health, their dysregulation can contribute to chronic inflammation and neurodegeneration in conditions such as Alzheimer's disease, Parkinson's disease, multiple sclerosis and amyotrophic lateral sclerosis. Additionally, astrocytes exhibit regional heterogeneity in their immune behaviors, which may influence disease trajectories. We highlight unresolved questions regarding the immune functions of astrocytes, their interplay with professional immune cells and their dual protective and pathological roles.},
}

*Astrocytes/immunology/metabolism
Humans
*Immunity, Innate/immunology
Animals
*Signal Transduction/immunology
Toll-Like Receptors/metabolism/immunology
Innate Immunity Recognition
Inflammasomes/metabolism/immunology

@article {pmid42373968,
year = {2026},
author = {Gardner, KL and Lange, TE and Perna, MK and Wells, SI and Williams, MT and Vorhees, CV and Cox, M and Solomon, MB and Privette Vinnedge, LM},
title = {DEK Loss Induces Task-specific Deficits in Learning and Memory and Reprograms the Hippocampal Transcriptome in Mice.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {42373968},
issn = {1559-1182},
mesh = {Animals ; *Hippocampus/metabolism ; Male ; *Poly-ADP-Ribose Binding Proteins/deficiency/metabolism/genetics ; *Chromosomal Proteins, Non-Histone/deficiency/metabolism/genetics ; Female ; *Oncogene Proteins/deficiency/metabolism/genetics ; *Transcriptome/genetics ; Mice, Knockout ; *Memory/physiology ; Mice, Inbred C57BL ; Mice ; Maze Learning ; Behavior, Animal ; DNA-Binding Proteins ; },
abstract = {DEK is an estrogen-responsive chromatin-remodeling protein broadly expressed in the murine and human brain, with high expression in memory-relevant regions such as the hippocampus. Prior work from our group and others has linked DEK loss to cellular features associated with Alzheimer's disease and Alzheimer's disease-related dementias. Notably, our group has demonstrated that DEK expression declines with increasing dementia severity in women, but not in age-matched men, suggesting a sex-specific relationship between DEK loss and cognitive vulnerability. Together, these findings support a potential neuroprotective role for DEK; however, functional consequences of DEK loss in vivo were unknown. Here, we examined behavioral and molecular consequences of Dek loss using male and female constitutive knockout (cKO) mice assessed across cognitive, sensorimotor, and affective domains. Across assays, Dek cKO mice of both sexes exhibited intact locomotor activity, anxiety-related behavior, sensorimotor gating, and fear-associated memory. In contrast, female Dek cKO mice displayed selective impairments in cognitive flexibility despite preserved spatial learning and memory, a phenotype not observed in males and indicative of female-specific vulnerability following DEK loss. This sex difference, observed during Morris water maze reversal learning, suggests disruption of hippocampal-prefrontal circuitry. Guided by known sex differences in hippocampal DEK expression, transcriptomic profiling of hippocampal tissue revealed shared and sex-specific consequences of Dek deficiency, including alterations in cytoskeletal organization, neuronal signaling, chromatin regulatory mechanisms, and cellular stress pathways. Collectively, these findings demonstrate sex- and cognitive-domain-specific effects of DEK loss and support further investigation of DEK in executive function and hippocampal-prefrontal cortex-mediated cognition.},
}

Animals
*Hippocampus/metabolism
Male
*Poly-ADP-Ribose Binding Proteins/deficiency/metabolism/genetics
*Chromosomal Proteins, Non-Histone/deficiency/metabolism/genetics
Female
*Oncogene Proteins/deficiency/metabolism/genetics
*Transcriptome/genetics
Mice, Knockout
*Memory/physiology
Mice, Inbred C57BL
Mice
Maze Learning
Behavior, Animal
DNA-Binding Proteins

@article {pmid42374181,
year = {2026},
author = {Gong, R and Wang, H and Cao, L and Niu, H and Rominger, A and Luo, Z and Ni, R},
title = {Targeting the crosstalk between Alzheimer's disease and gastrointestinal cancers.},
journal = {Molecular medicine (Cambridge, Mass.)},
volume = {},
number = {},
pages = {},
doi = {10.1186/s10020-026-01545-x},
pmid = {42374181},
issn = {1528-3658},
abstract = {Epidemiological studies have revealed an inverse association between Alzheimer's disease and cancer. Here, we discuss the mechanisms involved in the relationship between Alzheimer's disease and gastrointestinal cancers, particularly pancreatic and gastric-colorectal cancers. The gut‒brain axis and pancreas‒brain axis connect the central nervous system with peripheral organs and form immune‒metabolic networks. We focus on bidirectional tumor-brain communication, involving cell-death pathways, apoptosis, metabolic dysregulation, microbiota, metabolic dysregulation, neuroinflammation, immune system and sensory-sympathetic circuits, and neural remodeling. Furthermore, we discuss potential integrated, multitarget therapeutic strategies, including metabolic regulation, microbiome interventions, and immune modulation. Prospective longitudinal cohorts incorporating prediagnostic exposures and molecular pathology are needed to establish temporality.},
}

@article {pmid42374285,
year = {2026},
author = {Pedersen, EK and Nielsen, A and Nicolaisdóttir, DR and Øksnebjerg, L and Tannebæk, K and Janbek, J and Waldemar, G and Nielsen, TR},
title = {Associations between a psychosocial intervention and quality of life and caregiver-related outcomes in family caregivers of people with dementia: the Danish DemTool trial.},
journal = {BMC geriatrics},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12877-026-07835-7},
pmid = {42374285},
issn = {1471-2318},
abstract = {BACKGROUND: People with dementia often need comprehensive support, depending on the stage of the disease, from both family members and healthcare professionals. Caring for a person with dementia can be stressful and impact the caregiver's health and wellbeing. Studies show that family caregivers of people with dementia frequently experience stress, depression, and reduced quality of life. We aimed to assess the association between the psychosocial intervention (DemTool) and caregiver wellbeing and quality of life among family caregivers of people with dementia.

METHOD: DemTool trial was a pragmatic, cluster-controlled trial. The intervention was delivered by primary care dementia coordinators across 30 Danish municipalities from 2020 to 2023, with 15 serving as the intervention group and 15 as treatment as usual. The primary outcome measures were the Neuropsychiatric Inventory Caregiver Distress Scale (NPI-D) and the European Quality of Life Visual Analog Scale (EQ VAS). Both measures were completed at baseline and follow-up, alongside secondary quality of life outcomes. To estimate group differences in primary and secondary outcomes, we applied analysis of variance (ANOVA) and analysis of covariance (ANCOVA).

RESULTS: A total of 245 family caregivers were included in the study (181 in the intervention group and 64 in the treatment-as-usual group). Most participants were females caring for a spouse. Baseline scores for caregiver wellbeing and quality of life were similar across groups. The DemTool intervention was associated with a significant between-group difference in change from baseline in caregiver-related quality of life as measured by the Carer Experience Scale (CES), favoring the intervention. This was evident in the analysis adjusted for baseline scores (p = 0.05) and remained significant when further adjusting for caregiver-related covariates (p = 0.02). No statistically significant between-group differences were observed for the remaining wellbeing and quality-of-life outcomes.

CONCLUSION: No effects of DemTool were found on traditional health-related quality-of-life outcomes. However, a positive association was found between the intervention and the CES, underlining the importance of selecting outcomes that are directly related to the targeted effects of the intervention.

TRIAL REGISTRATION: The study protocol was registered in the ClinicalTrials.gov system, registration number: NCT07355829.},
}

@article {pmid42374489,
year = {2026},
author = {Saul, E and Chauveau, L and Landeau, B and Lasserve, J and Montagne, B and Foyard, E and Poisnel, G and Chételat, G and de Flores, R and , },
title = {Structural and molecular determinants of medial temporal lobe network vulnerability in aging and Alzheimer's disease.},
journal = {Alzheimer's research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13195-026-02125-1},
pmid = {42374489},
issn = {1758-9193},
support = {667696//European Union's Horizon 2020 Research and Innovation Program/ ; },
abstract = {BACKGROUND: The medial temporal lobe is organized into two memory-critical networks: the anterior-temporal and posterior-medial systems. While these systems show selective vulnerability to aging and Alzheimer's disease, the underlying structural and molecular determinants of this susceptibility remain unclear. We aimed to characterize the specific white matter pathways supporting these networks, investigate how amyloid-β and neuroinflammation interact to impact their integrity, and determine if structural changes relate to functional connectivity alterations.

METHODS: In 88 cognitively unimpaired (CU) older adults (≥ 65 years) from the Age-Well cohort (NCT02977819), we combined longitudinal diffusion MRI tractography, resting-state fMRI, amyloid-β PET (Florbetapir), and plasma glial fibrillary acidic protein (GFAP). We reconstructed fiber pathways of the perirhinal (anterior-temporal system hub) and parahippocampal (posterior-medial system hub) cortices and quantified their microstructural integrity, network connectivity, and relationships to pathology.

RESULTS: The anterior-temporal and posterior-medial systems relied on partly distinct structural pathways. Both involved the inferior longitudinal and cingulum bundles, but the anterior-temporal system was specifically associated to their inferior portions, as well as thalamic radiations, and callosal fibers, whereas the posterior-medial system relied more on their superior portions and the inferior fronto-occipital fasciculus. We identified a non-linear, inverted U-shaped association between pathway integrity and amyloid-β burden, suggesting dynamic structural changes across early pathological stages. Crucially, plasma GFAP moderated this relationship for the posterior-medial pathway: the negative impact of amyloid-β on structural integrity was exacerbated in individuals with higher astroglial reactivity, highlighting a synergistic pathological effect. Finally, in high amyloid-β individuals, increased anterior-temporal functional connectivity correlated with lower anterior-temporal pathway integrity, suggesting that network higher FC may represent a maladaptive response to early amyloid-β deposition leading to white matter integrity loss.

CONCLUSIONS: Together, our findings reveal distinct mechanisms of vulnerability within medial temporal networks: while the posterior-medial system is primarily sensitive to the synergistic effects of amyloid-β and astroglial reactivity, the anterior-temporal system shows lower structural integrity linked to higher FC in the presence of amyloid. By providing a mechanistic framework for these early disruptions, this study advances the understanding of preclinical Alzheimer's disease and identifies specific structural-functional signatures that could serve as sensitive biomarkers for targeted interventions.},
}

@article {pmid42374501,
year = {2026},
author = {Bregman, N and de Barros, NP and Nathan, T and Levy, MH and Sima, D and Van Eyndhoven, S and Bar-David, A and Aizenstein, O and Niry, D and Atlan, L and Awad, AA and Ash, E and Omer, N and Shiner, T},
title = {Lecanemab in practice: AI-derived MRI predictors of benefit and Amyloid Related Imaging Abnormalities (ARIA).},
journal = {Alzheimer's research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13195-026-02127-z},
pmid = {42374501},
issn = {1758-9193},
abstract = {INTRODUCTION: Lecanemab, a monoclonal antibody targeting amyloid beta, has demonstrated meaningful clinical benefits in early Alzheimer's disease (AD), yet real-world data is needed to optimize patient selection and enhance safety monitoring, particularly with respect to amyloid-related imaging abnormalities (ARIA). Integration of quantitative and AI-derived MRI biomarkers may improve risk stratification and prediction of clinical trajectory.

METHODS: We conducted a retrospective real-world study of eighty-two patients with biomarker-confirmed early AD who initiated lecanemab at Tel Aviv Sourasky Medical Center between November 2023 and June 2025. Baseline MRI included volumetric T1-weighted imaging and susceptibility-weighted imaging (SWI). Automated whole-brain, regional cortical, and hippocampal volumes, and percentiles were extracted using FDA-cleared AI tools (icobrain by icometrix). Microhaemorrhage (MH) burden was assessed by both human and AI-assisted reads. Cognitive outcomes were evaluated using change in Mini-Mental State Examination (MMSE). Linear regression models assessed MRI predictors of cognitive response, and multivariable logistic regression identified predictors of ARIA.

RESULTS: Patients exhibited significantly lower cerebral volumes at treatment initiation. Mean whole brain percentile, mean gray-matter (GM) percentile, and mean white matter percentile were 11.45%, 8.6% and 38% respectively. Higher baseline GM volume predicted less MMSE decline at 12 months (β = 0.64, FDR-corrected p < 0.003). Hippocampal and white-matter volumes were not associated with cognitive outcomes. Seventeen patients (20.7%) developed ARIA. Baseline MH burden was the strongest predictor of ARIA (human rated OR=3.48 per MH, p=0.015, icobrain rated OR=3.25, p=0.01), while APOE ε4 carriage showed a strong directional trend which did not reach significance. Aspirin use and hypertension were not associated with ARIA. Agreement between icobrain and experts for MH ratings was excellent with a single-measure intraclass correlation coefficient (ICC) of 0.89 (95% CI: 0.83-0.93).

CONCLUSIONS: AI-derived MRI markers, particularly GM volume and MH burden, provide valuable predictors of cognitive response and ARIA risk in patients treated with lecanemab. Integrating quantitative neuroimaging into clinical workflows may enhance personalized treatment decisions and improve real-world implementation of Amyloid-targeting therapies.},
}

@article {pmid42374538,
year = {2026},
author = {Moon, SH and Kim, MH and Ryoo, JH},
title = {Smoking cessation duration and risk of Alzheimer's disease: a nationwide cohort study in Korea.},
journal = {Alzheimer's research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13195-026-02132-2},
pmid = {42374538},
issn = {1758-9193},
support = {RS-2024-00509118//Ministry of Health and Welfare/ ; },
abstract = {BACKGROUND: Smoking is a modifiable risk factor for Alzheimer's disease, yet the temporal pattern of risk reduction following smoking cessation remains unclear. We investigated whether Alzheimer's disease risk declines according to the duration of sustained smoking cessation in a large nationwide cohort.

METHODS: Using the Korean National Health Insurance Service database (2002-2023), we identified 1,403,636 adults with stable longitudinal smoking patterns based on repeated biennial health examinations. Smoking status was classified as never smokers, current smokers, or sustained quitters, with cessation duration categorised into 2-year intervals (< 2, 2-3, 4-5, 6-7, ≥ 8 years). Incident Alzheimer's disease was defined as at least two separate NHIS insurance claims. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals, adjusting for demographic, lifestyle, and metabolic factors.

RESULTS: During a mean follow-up of 10.5 years, 58,519 incident Alzheimer's disease cases were identified. Compared with current smokers, sustained quitters exhibited progressively lower hazards of Alzheimer's disease with increasing duration of abstinence, demonstrating a dose-response pattern. Individuals who had quit for < 2 years showed a risk reduction relative to current smokers (adjusted HR 0.899; 95% CI 0.819-0.986), while those with ≥ 8 years of abstinence had substantially lower risk (adjusted HR 0.582; 95% CI 0.423-0.801). When referenced to never smokers, those with < 2 years of abstinence retained excess risk, whereas cessation for ≥ 2 years was associated with Alzheimer's disease risk approaching that of never smokers.

CONCLUSIONS: Sustained smoking cessation was associated with a graded reduction in Alzheimer's disease risk, with approximately 2 years of abstinence needed to approach never-smoker risk.},
}

@article {pmid42374761,
year = {2026},
author = {Xing, Z and Jiang, X and Yang, W and Wang, Y and Zhang, X and Zhao, C},
title = {Corrigendum to: Lithium Chloride Improves Electrophysiological and Memory Deficits in Rats with Streptozotocin-Induced Alzheimer's Disease.},
journal = {Current Alzheimer research},
volume = {23},
number = {1},
pages = {75},
doi = {10.2174/1567205023999260119152707},
pmid = {42374761},
issn = {1875-5828},
abstract = {In the published version of this article [1], the email address of the co-corresponding author, Zheng Xing, was missing from the corresponding address section. This has now been corrected. The original article can be found online at: https://www.eurekaselect.com/article/149786 Details of the error and the correction are provided below: Original: Address correspondence to this author at the Department of Pharmacy, The Second People's Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical University, Changzhou, Jiangsu, 213004, P.R. China; E-mail: zhaochen3339@njmu.edu.cn (C.Z.); Corrected: Address correspondence to these authors at the Department of Pharmacy, The Second People's Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical University, Changzhou, Jiangsu, 213004, P.R. China; E-mails: zhaochen3339@njmu.edu.cn (C.Z.); xingzheng@cczu.edu.cn (Z.X.).},
}

@article {pmid42374762,
year = {2026},
author = {Boudi, A and He, J and El Kader, IA and Liu, X and Mouhafid, M},
title = {Corrigendum to: Advancing Alzheimer's Disease Diagnosis Using VGG19 and XGBoost: A Neuroimaging-Based Method.},
journal = {Current Alzheimer research},
volume = {23},
number = {1},
pages = {76},
doi = {10.2174/1567205023999260119151250},
pmid = {42374762},
issn = {1875-5828},
abstract = {The publisher identified that references 42 and 43 were duplicated in the published version of this article [1]. The error has now been corrected. The original article can be found online at: https://www.benthamscience.com/article/150567 Details of the error and the correction are provided below: Original: [42] Muksimova S, Umirzakova S, Iskhakova N, Khaitov A, Cho YI. Advanced convolutional neural network with attention mechanism for Alzheimer's disease classification using MRI. Comput Biol Med 2025; 190, 110095. [43] Muksimova S, Umirzakova S, Iskhakova N, Khaitov A, Cho YI. Advanced convolutional neural network with attention mechanism for Alzheimer's disease classification using MRI. Comput Biol Med 2025; 190: 110095. http://dx.doi.org/10.1016/j.compbiomed.2025.110095 PMID: 40158456 Corrected: [42] Muksimova S, Umirzakova S, Iskhakova N, Khaitov A, Cho YI. Advanced convolutional neural network with attention mechanism for Alzheimer's disease classification using MRI. Comput Biol Med 2025; 190, 110095. http://dx.doi.org/10.1016/j.compbiomed.2025.110095 PMID: 40158456 [43] Olaimat MA, Bozdag S, Saeed F. TA-RNN: An attention-based time-aware recurrent neural network architecture to predict progression of Alzheimer's disease. Alzheimer's Dement 2024; 20(S1).},
}

@article {pmid42374773,
year = {2026},
author = {Kim, H and Liu, E and Kajiyama, B and Song, J and Paun, O and Han, SG and Gallagher-Thompson, D},
title = {Development of K-iCare: a culturally adapted stress management intervention for Korean American dementia family caregivers.},
journal = {Aging & mental health},
volume = {},
number = {},
pages = {1-11},
doi = {10.1080/13607863.2026.2693238},
pmid = {42374773},
issn = {1364-6915},
abstract = {OBJECTIVES: We developed the Korean version of iCare (K-iCare), a cognitive behavioral therapy (CBT)-based stress management intervention for Korean American family caregivers of individuals with Alzheimer's disease and related dementias (ADRD).

METHODS: Using the Framework for Reporting Adaptations and Modifications-Enhanced (FRAME), K-iCare was developed through a five-stage process: (1) initial modifications by the research team; (2) feedback from two focus groups comprising former Korean American ADRD family caregivers and Korean American community service providers; (3) refinement of K-iCare; (4) validation by focus group participants and the original iCare developers; and (5) finalization for implementation.

RESULTS: Intervention materials were translated into Korean with systematic cultural and linguistic adaptations. The number of chapters was consolidated from nine to five, and caregiving scenarios were replaced with culturally relevant examples reflecting Korean American caregiving norms. The intervention format was revised from self-paced, asynchronous modules to synchronous weekly small-group sessions delivered in a hybrid format and led by a bilingual, bicultural, doctoral-level interventionist with expertise in ADRD care. Supporting materials (e.g. fidelity monitoring checklists) were developed to promote consistent intervention delivery.

CONCLUSION: The next phase will evaluate the feasibility and acceptability of K-iCare and generate preliminary estimates of intervention-associated change and outcome variability.},
}

@article {pmid42374809,
year = {2026},
author = {Jiang, B and Yan, Y and Xu, C and Zhao, X and Qi, F and Xu, S and Yang, W and Liu, X and Feng, L},
title = {Herpes zoster as a vaccine-preventable risk factor increases the risk of dementia: A nested case-control study in Chinese population.},
journal = {Human vaccines & immunotherapeutics},
volume = {22},
number = {1},
pages = {2681253},
doi = {10.1080/21645515.2026.2681253},
pmid = {42374809},
issn = {2164-554X},
mesh = {Humans ; *Herpes Zoster/complications/prevention & control/epidemiology ; Case-Control Studies ; Female ; China/epidemiology ; Risk Factors ; *Dementia/epidemiology/etiology ; Male ; Aged ; Middle Aged ; Aged, 80 and over ; East Asian People ; },
abstract = {Herpes zoster, a vaccine-preventable disease caused by the reactivation of varicella-zoster virus, has been linked to an increased risk of dementia in high-income countries. However, evidence from populations with low vaccination coverage remains limited. To address this gap, we conducted a nested case-control study using electronic health records from Yichang, China. A total of 51,843 incident dementia patients aged 50 y and older were matched with 338,877 controls by sex, age, and visit date. A documented clinical history of herpes zoster was significantly associated with an elevated risk of all-cause dementia (adjusted odds ratio [aOR] = 1.48; 95% confidence interval [CI]: 1.41-1.56), with the highest risk observed among individuals with herpes zoster involving the central nervous system (aOR = 1.59, 95%CI: 1.46-1.73). Among the dementia cases with prior HZ diagnosis, both Alzheimer's disease (aOR = 1.44, 95%CI: 1.14-1.79) and vascular dementia (aOR = 1.82, 95%CI: 1.49-2.21) showed increased risks following herpes zoster infection, with vascular dementia demonstrating a stronger association and more rapid progression (median time from first herpes zoster diagnosis to dementia onset: 1.5 y versus 2.2 y for Alzheimer's disease). The findings, derived from a population with minimal herpes zoster vaccination coverage, identify herpes zoster as a potentially modifiable risk factor for dementia. These also underscore the potential dual public health benefit of herpes zoster vaccination in preventing both acute infection and long-term cognitive decline.},
}

Humans
*Herpes Zoster/complications/prevention & control/epidemiology
Case-Control Studies
Female
China/epidemiology
Risk Factors
*Dementia/epidemiology/etiology
Male
Aged
Middle Aged
Aged, 80 and over
East Asian People

@article {pmid42375090,
year = {2026},
author = {Lee, HY and Hossain, MK and Jang, GH and Lee, H and Kim, YM and Chae, HJ},
title = {Behavioral and Biochemical Evaluation of a Curcumin-Loaded Nano-Liposomal Formulation in a Scopolamine-Induced Mouse Model of Cognitive Impairment.},
journal = {Biomolecules & therapeutics},
volume = {34},
number = {4},
pages = {866-881},
doi = {10.4062/biomolther.2026.062},
pmid = {42375090},
issn = {1976-9148},
abstract = {Scopolamine-induced cognitive impairment in mice models acute cholinergic dysfunction associated with early functional features of Alzheimer's disease (AD). This study evaluated the neuroprotective potential of curcumin-loaded nanoliposomes (Cur-NL), a bioavailable curcumin formulation, using behavioral, molecular, and biochemical approaches. Male mice received oral Cur-NL (250, 500, or 1000 mg/kg) for 30 days, followed by a single intraperitoneal injection of scopolamine (2 mg/kg). Cognitive performance was assessed by the open field test and Barnes maze. Acetylcholinesterase (AChE) activity, acetylcholine (ACh) levels, hippocampal gene expression, and reactive oxygen species (ROS) accumulation were analyzed to investigate underlying mechanisms. Cur-NL significantly improved spatial learning and memory and restored cholinergic balance by normalizing AChE activity and ACh levels. Treatment also attenuated hippocampal neuroinflammation, oxidative stress, and ROS accumulation. Cur-NL modulated genes related to amyloid processing and synaptic plasticity, suppressing App and Bace1 and upregulating Adam10 and Bdnf. Network analyses supported the involvement of cholinergic, inflammatory, and synaptic signaling pathways. These findings indicate that Cur-NL confers multitarget neuroprotection in a scopolamine-induced model and may serve as a candidate for managing early cholinergic-related cognitive decline. Important limitations should be acknowledged: curcumin concentrations in plasma and brain were not quantified, and a free-curcumin comparator was not included. The findings should therefore be interpreted as evidence of efficacy of the tested Cur-NL preparation, not as a comparative demonstration of nano-liposomal superiority over free curcumin. Direct pharmacokinetic and head-to-head comparative studies are required to establish the formulation-specific contribution of nano-liposomal delivery.},
}

@article {pmid42375607,
year = {2026},
author = {Lee, N and Youn, K and Kwon, H and Kim, DH and Ho, CT and Jun, M},
title = {Fucoxanthin attenuates carbonyl stress and neuroinflammation by modulating MGO/RAGE/NF-κB axis in Aβ-induced models.},
journal = {Frontiers in pharmacology},
volume = {17},
number = {},
pages = {1811183},
pmid = {42375607},
issn = {1663-9812},
abstract = {INTRODUCTION: Amyloid-β (Aβ) accumulation is a central pathological feature of Alzheimer's disease (AD) and a major driver of disease progression. Recent evidence suggests that carbonyl stress associated with Aβ plays a critical role in AD pathology by promoting neuroinflammation and neuronal damage. In particular, methylglyoxal (MGO), a highly reactive carbonyl compound, contributes to activation of the receptor for advanced glycation end products (RAGE) and NF-κB-dependent inflammatory signaling, leading to synaptic dysfunction. The present study investigated whether fucoxanthin, a marine-derived carotenoid, attenuates Aβ-induced carbonyl stress and inflammatory responses associated with MGO/RAGE/NF-κB-related signaling.

METHODS: PC12 neuronal cells were pretreated with fucoxanthin (0.1-5 μM) and exposed to aggregated Aβ25-35 (10 μM) to assess its effects on carbonyl stress-associated inflammatory signaling. In parallel, an Aβ1-42 intracerebroventricular injection mouse model was used to validate the in vitro findings. Mice were orally administered fucoxanthin (100 or 200 mg/kg/day) for 15 days and assessed for serum MGO levels, hippocampal RAGE/NF-κB activation, microglial activation, and synaptic marker expression.

RESULTS: Fucoxanthin significantly reduced the expression of pro-inflammatory mediators, including COX-2, iNOS, IL-1β, and TNF-α in Aβ-exposed neuronal cells. This anti-inflammatory effect was associated with inhibition of NF-κB nuclear translocation and downregulation of RAGE expression. Consistent with these in vitro findings, fucoxanthin treatment in Aβ1-42-injected mice alleviated systemic and hippocampal carbonyl stress, as evidenced by decreased serum MGO levels and suppression of hippocampal RAGE/NF-κB activation. These effects were accompanied by reduced microglial activation (Iba-1) across hippocampal subregions and significant restoration of both presynaptic and postsynaptic markers, indicating preservation of synaptic integrity.

CONCLUSION: These findings demonstrate the neuroprotective role of fucoxanthin in mitigating Aβ-induced carbonyl stress by targeting the MGO/RAGE/NF-κB axis, thereby suppressing neuroinflammation and preserving synaptic integrity in Aβ-induced cellular and mouse models. Fucoxanthin emerges as a promising pharmacological candidate targeting carbonyl stress-associated mechanisms in AD.},
}

@article {pmid42375805,
year = {2025},
author = {Castro-Fuentes, R and Socas-Pérez, R},
title = {Unveiling the significance of dog domestication in cognitive dysfunction: Are wolves protected?.},
journal = {Open veterinary journal},
volume = {15},
number = {2},
pages = {6126-6145},
pmid = {42375805},
issn = {2218-6050},
mesh = {Animals ; *Wolves ; Dogs ; *Domestication ; *Cognitive Dysfunction/etiology/epidemiology ; *Dog Diseases/etiology ; Risk Factors ; Aging ; },
abstract = {Over the course of their long coexistence with humans, dogs have developed a stronger bond with humans than with any other domestic species. This close relationship has promoted notable parallels in both genetics and lifestyle, thereby facilitating the development of comparable pathological conditions, including several central nervous system disorders. Canine cognitive dysfunction (CCD) is a spontaneous model of neurodegeneration that shares clinical features, neuropathological characteristics, and risk factors with human Alzheimer's disease (AD). However, the potential role of dog domestication in increasing CCD susceptibility remains poorly explored. In this sense, the gray wolf (Canis lupus), a direct ancestor of the domestic dog (Canis lupus familiaris), represents a comparative model of great interest, as the information available on its neuropathology and behavior associated with aging is very limited. To provide a preliminary framework for assessing how domestication may have shaped vulnerability to cognitive decline in canids, this study employed a database-driven analytical approach to evaluate the degree of impact of various risk factors shared by AD and CCD-including aging, oxidative stress, inflammation, sleep disturbances, and periodontal disease-in domestic dogs and gray wolves kept in captivity or semi-captivity. Our results indicate that domestic dogs have more pronounced key risk factors for CCD than captive or semi-captive gray wolves. This finding suggests that wolves may be less vulnerable to age-related cognitive dysfunction, possibly reflecting differences in evolutionary or domestication processes. Nevertheless, given the scarcity of neuropathological and behavioral data on aged wolves, these conclusions should be interpreted with caution, and further direct investigations are warranted. Domestication may have increased susceptibility to age-related cognitive dysfunction in dogs by enhancing exposure to key risk factors, as oxidative stress, inflammation, and lifestyle-related conditions. Recognizing these domestication-linked vulnerabilities highlights the need for preventive health strategies in dogs and provides a valuable comparative framework for understanding neurodegenerative processes across species within a One Health perspective.},
}

Animals
*Wolves
Dogs
*Domestication
*Cognitive Dysfunction/etiology/epidemiology
*Dog Diseases/etiology
Risk Factors
Aging

@article {pmid42375925,
year = {2026},
author = {Sujanthi, S and Ravishankkar, AM and Ponmaniraj, S and Nanthini, S},
title = {Magnetic resonance imaging-based Alzheimer's disease detection using an EfficientNet-CMSACCN framework.},
journal = {Cytotechnology},
volume = {78},
number = {4},
pages = {146},
pmid = {42375925},
issn = {0920-9069},
abstract = {Alzheimer's Disease (AD) is a degenerative neurological condition characterized by memory loss, cognitive deterioration, and brain tissue shrinkage. Detecting it at an early stage is difficult due to variations in disease progression and the restricted scope of single-modality neuroimaging methods. Magnetic Resonance Imaging (MRI)-based Alzheimer's diagnosis, such as magnetic resonance imaging, offers complementary structural and functional insights, but existing deep learning methods often struggle with data imbalance, high computational complexity, and limited generalization. To fill these research gaps, design an MRI-based EfficientNet feature extraction framework for Alzheimer's stage classification. EfficientNet, equipped with compound scaling, depthwise-separable layers, and squeeze-and-excitation components, enables precise characterization of cortical structures and whole-brain variations while preserving computational efficiency. Extracted features are classified using a Compression-based Multi-Scale Attention Convolutional Network (C-MSACCN), which integrates attention mechanisms and compression strategies to enhance accuracy and reduce model complexity. Furthermore, the Improved Cellular Neighbours Optimiser (ICNO) fine-tunes hyperparameters, striking a balance between exploration and exploitation for optimal convergence and robustness. With 99.9% accuracy, precision, recall, and F1-score on datasets, the model outperforms prior work. Validation confirms consistency, and visualisation methods highlight disease-relevant regions to provide clinical insight.},
}

@article {pmid42376002,
year = {2026},
author = {Paitel, ER and Pettigrew, C and Moghekar, A and Miller, MI and Faria, AV and Albert, M and Na, CH and Worley, P and Soldan, A},
title = {Associations of cerebrospinal fluid measures of synaptic function with white matter microstructure and cognition in older adults.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1851829},
pmid = {42376002},
issn = {1663-4365},
abstract = {INTRODUCTION: Lower levels of several synaptic proteins in cerebrospinal fluid (CSF) have been associated with greater cognitive decline among older adults, but there is limited understanding of their associations with brain structure. This study is among the first to examine the cross-sectional relationship between levels of three synaptic proteins (VGF, NPTX2, and GluA4) with magnetic resonance imaging (MRI) measures of white matter microstructure and volumes, and with cognitive performance. We also examined whether relationships between synaptic protein levels and white matter measures are influenced by CSF Alzheimer's disease (AD) biomarker levels [ratio of p-tau181/(Aβ42/Aβ40)].

METHODS: Participants included 151 middle-aged and older adults without dementia (132 cognitively unimpaired, 19 mild cognitive impairment, M age = 69.3 years). White matter volumes and microstructure [fractional anisotropy (FA), mean diffusivity (MD)], derived from MRI scans, were assessed in three regions: global cerebral, medial temporal lobe, and cerebellar peduncles.

RESULTS: In linear regression analyses, lower levels of NPTX2, VGF, and GluA4 were associated with lower FA and higher MD, even after accounting for CSF AD biomarker levels. Synaptic proteins were not associated with white matter volumes. Additionally, lower FA, higher MD, and lower VGF levels were associated with poorer executive function performance. An exploratory mediation analysis showed that cerebral white matter MD statistically mediated the relationship between VGF and executive performance.

DISCUSSION: These findings provide preliminary, cross-sectional support that VGF may act on cognition via white matter microstructure. Together the results suggest that white matter microstructure may represent one pathway linking synaptic proteins levels to cognitive performance among older adults. Future research is needed to advance understanding of the specific mechanisms driving these relationships.},
}

@article {pmid42376437,
year = {2026},
author = {Dominguez, LJ and Veronese, N and Ragusa, FS and Seminara, F and Baio, SM and Vernuccio, L and Catanese, G and Barbagallo, M},
title = {Prevention of cognitive decline and dementia: Current evidence on lifestyle factors and dietary patterns.},
journal = {EXCLI journal},
volume = {25},
number = {},
pages = {690-724},
pmid = {42376437},
issn = {1611-2156},
abstract = {Cognitive decline and dementia represent major and growing global health challenges, driven largely by population aging and increased longevity. Currently, more than 55 million people worldwide live with dementia, a figure projected to rise to approximately 153 million by 2050. Alzheimer's disease accounts for the majority of cases, and despite extensive research, effective disease-modifying therapies remain limited. Consequently, increasing attention has shifted toward prevention strategies targeting modifiable risk factors. Accumulating evidence indicates that dementia is not an inevitable consequence of aging and that up to 45 % of cases may be attributable to potentially modifiable lifestyle and environmental factors operating across the life course. Lifestyle behaviors-including diet, physical activity, smoking, alcohol consumption, sleep, and social and cognitive engagement-have emerged as key targets for intervention. In particular, adherence to healthy dietary patterns such as the Mediterranean, DASH, and MIND diets has been associated with better cognitive outcomes, while unhealthy dietary patterns may increase risk. However, findings across studies remain heterogeneous, and uncertainties persist regarding causality, optimal exposure timing, and specific lifestyle components. Recent large prospective cohorts, meta-analyses, umbrella reviews, and multidomain intervention trials have advanced understanding of these associations but have also highlighted important gaps, including limited randomized evidence and underrepresentation of diverse populations. This narrative review critically synthesizes current evidence on lifestyle factors and dietary patterns associated with cognitive decline and dementia risk, focusing on recent high-quality studies. By integrating findings across domains, it aims to clarify areas of consensus and uncertainty, inform prevention strategies, and identify priorities for future research and public health action. See also the graphical abstract(Fig. 1).},
}