@article {pmid42828019,
year = {2026},
author = {Kucukbagriacik, Y and Saribas, GS and Ates, K and Ozturk, C and Kahyaoglu, E and Kislal, S and Akgul, CC and Karacalioglu, AO and Goksoy, C and Kantarcioglu, M},
title = {Exploratory effects of coffee-derived exosome-like nanoparticles in a fibrillar amyloid-beta 1-42-induced neurodegenerative rat model: evidence from fluorodeoxyglucose positron emission tomography and phosphorylated tau/amyloid precursor protein expression.},
journal = {PeerJ},
volume = {14},
number = {},
pages = {e21739},
pmid = {42828019},
issn = {2167-8359},
mesh = {Animals ; Male ; *Amyloid beta-Peptides/metabolism ; Rats, Sprague-Dawley ; *tau Proteins/metabolism ; *Nanoparticles/chemistry/administration & dosage ; *Exosomes/chemistry ; Peptide Fragments ; Rats ; Phosphorylation ; Disease Models, Animal ; *Coffee/chemistry ; Fluorodeoxyglucose F18 ; *Alzheimer Disease/drug therapy/diagnostic imaging/metabolism ; *Amyloid beta-Protein Precursor/metabolism ; Positron-Emission Tomography ; },
abstract = {BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-beta 1-42 (Aβ1-42) accumulation, tau pathology, and metabolic dysfunction. This exploratory study evaluated the effects of coffee-derived exosome-like nanoparticles (CELNs) on selected metabolic and histopathological endpoints in a fibrillar Aβ1-42-induced neurodegenerative rat model.

METHODS: Fifty male Sprague-Dawley rats were randomly divided into five groups (N = 10 each): Control (C), sham (SF), a fibrillar Aβ1-42-induced neurodegenerative rat model (AD), AD treated with a low dose of CELNs (AD + LE, 10 mg/kg/day), and AD treated with a high dose of CELNs (AD + HE, 20 mg/kg/day) for 14 days. CELNs were quantified and characterized using the bicinchoninic acid method, scanning electron microscopy, and nanoparticle tracking analysis (NTA). Micro-positron emission tomography/computed tomography fluorodeoxyglucose (MicroPET/CT FDG) imaging of the central nervous system was performed in all groups at the end of treatment. Subsequently, all animals were sacrificed, and hippocampal tissues were subjected to histopathological analysis.

RESULTS: MicroPET imaging demonstrated a significant, dose-dependent increase in cerebral glucose metabolism in AD rats treated with CELNs compared with the untreated AD group. Histopathological evaluations were consistent with the imaging data: in AD groups receiving CELNs, phospho-tau and beta-amyloid precursor protein expression were significantly reduced in the hippocampal cornu ammonis 2 (CA2) and dentate gyrus regions compared with the untreated AD group.

CONCLUSIONS: In this exploratory fibrillar Aβ1-42-induced neurodegenerative rat model, oral CELN administration was associated with dose-dependent partial improvements in cerebral glucose metabolism and region-specific reductions in hippocampal phosphorylated tau (p-Tau) and amyloid precursor protein (APP) immunoreactivity. However, these are preliminary biomarker-level findings that support further investigation of CELNs; definitive confirmation of functional and cognitive benefits requires additional behavioral, biodistribution, and experimental validation.},
}

Animals
Male
*Amyloid beta-Peptides/metabolism
Rats, Sprague-Dawley
*tau Proteins/metabolism
*Nanoparticles/chemistry/administration & dosage
*Exosomes/chemistry
Peptide Fragments
Rats
Phosphorylation
Disease Models, Animal
*Coffee/chemistry
Fluorodeoxyglucose F18
*Alzheimer Disease/drug therapy/diagnostic imaging/metabolism
*Amyloid beta-Protein Precursor/metabolism
Positron-Emission Tomography

@article {pmid42828025,
year = {2025},
author = {Zhang, S and Wang, Z and Kharrazi, H},
title = {RaiLED-AD: Rationale-Guided Knowledge Transfer for Alzheimer's Disease Prediction from Electronic Health Records.},
journal = {Proceedings. IEEE International Conference on Bioinformatics and Biomedicine},
volume = {2025},
number = {},
pages = {7673-7680},
pmid = {42828025},
issn = {2156-1125},
support = {R01 AG068002/AG/NIA NIH HHS/United States ; },
abstract = {In Alzheimer's Disease and Related Dementia (ADRD) prediction, Electronic Health Records (EHRs) provide rich but fragmented information. Without a coherent clinical narrative, models tend to rely on a few dominant signals (e.g., age-related patterns) rather than capturing the underlying clinical mechanisms. Such reliance becomes problematic in younger-onset cases, where these signals are less informative. To address this challenge, we propose RaiLED-AD, a dual-encoder teacher-student framework where the student learns from serialized EHR data and the teacher leverages LLM-generated narratives that capture temporal and relational patterns. A hybrid objective with soft-label supervision and hierarchical contrastive alignment transfers these reasoning signals to the student, which operates independently at inference. On a real-world EHR cohort, RaiLED-AD consistently improves ADRD prediction over baselines and achieves substantial gains in the challenging younger-onset subgroup (index age <65). These results highlight the potential of integrating LLM-derived reasoning signals with structured EHR models for early-stage ADRD risk prediction.},
}

@article {pmid42828275,
year = {2026},
author = {Law, KW and Engstrom, AC and Lohman, T and Quiring, M and Kapoor, A and Alitin, JPM and Wang, DJJ and Gaubert, A and Rodgers, K and Head, E and Valencia, CI and Joyce, JL and Ferrer, F and Nation, DA},
title = {Older adults in more disadvantaged neighborhoods exhibit brain vascular dysfunction.},
journal = {Cerebral circulation - cognition and behavior},
volume = {11},
number = {},
pages = {100562},
pmid = {42828275},
issn = {2666-2450},
abstract = {Neighborhood disadvantage is a risk factor for dementia, but the mechanisms involved are not well understood. In this study, we explored the relationship between neighborhood deprivation and whole-brain cerebrovascular reactivity (CVR) in 132 older adults without a history of clinical stroke or dementia. Participants underwent brain MRI and venipuncture. Relative neighborhood deprivation was quantified using the Area Deprivation Index. Spontaneous CVR was calculated as the percent change in resting cerebral blood flow per unit change in end-tidal CO2. Greater neighborhood deprivation was associated with lower whole-brain CVR when adjusted for age and sex (p = 0.027). Further adjustment for APOE ε4 carrier status, vascular risk factors, and plasma Alzheimer's disease (AD) biomarker p-tau217 did not alter the results. These findings show that older adults in more disadvantaged environments exhibit reduced cerebrovascular function, independent of traditional vascular risk and AD-related pathology. However, further investigation with more diverse samples and a life-course model is warranted to better understand these microvascular differences.},
}

@article {pmid42828354,
year = {2026},
author = {Dacey, R and Durape, S and Wang, M and Hwang, PH and Gurnani, AS and Ang, TFA and Devine, SA and Choi, SE and Lee, M and Scollard, P and Mukherjee, S and Trittschuh, E and Sherva, R and Dumitrescu, L and Hohman, TJ and Cuccaro, ML and Saykin, AJ and Crane, PK and Li, Y and Levy, D and Ma, J and Liu, C and Lunetta, KL and Au, R and Farrer, LA and Mez, J},
title = {Epigenetic Age and Resilience in the Framingham Heart Study.},
journal = {Neurology open access},
volume = {2},
number = {2},
pages = {},
pmid = {42828354},
issn = {2998-7601},
support = {U01 AG058654/AG/NIA NIH HHS/United States ; R01 AG016495/AG/NIA NIH HHS/United States ; P30 AG072978/AG/NIA NIH HHS/United States ; R01 AG008122/AG/NIA NIH HHS/United States ; N01 HC025195/HL/NHLBI NIH HHS/United States ; U01 AG062602/AG/NIA NIH HHS/United States ; U01 AG081230/AG/NIA NIH HHS/United States ; U19 AG068753/AG/NIA NIH HHS/United States ; RF1 AG054156/AG/NIA NIH HHS/United States ; R01 AG061028/AG/NIA NIH HHS/United States ; RF1 AG062109/AG/NIA NIH HHS/United States ; U24 AG074855/AG/NIA NIH HHS/United States ; R01 AA028263/AA/NIAAA NIH HHS/United States ; R01 AG033040/AG/NIA NIH HHS/United States ; R01 AG048927/AG/NIA NIH HHS/United States ; },
abstract = {BACKGROUND AND OBJECTIVES: Growing evidence suggests that decreased epigenetic age relative to chronological age may be protective against late-life cognitive decline and dementia, but the mechanism leading to this resilience is unknown.

METHODS: DNA methylation (DNAm), plasma total tau (t-tau), MRI total cerebral brain volume (TCBV), and neuropsychological (NP) data were obtained from Framingham Heart Study Offspring cohort participants. Three epigenetic age measures, DunedinPACE, PCPhenoAge, and PCGrimAge, were estimated from DNAm data. DunedinPACE and residuals from regressing PCPhenoAge and PCGrimAge on chronological age were standardized for analysis. Longitudinal NP factor scores were previously derived for memory, language, and executive function (EF) using confirmatory factor analysis. We tested the association of epigenetic age with cognitive trajectories using linear mixed-effects models and with time to mild cognitive impairment (MCI), Alzheimer disease dementia (AD), and all-cause dementia using Cox proportional hazard models and whether t-tau and TCBV moderated the observed relationships.

RESULTS: At baseline (Exam 8, 2005-2008), the sample included 2,606 participants [mean age: 66 (SD = 9) years, 55% female, mean education: 16 (SD = 3) years]. Epigenetic age measures were weakly but significantly (p < 0.001) correlated with t-tau (r: 0.08-0.12) and TCBV (r: -0.05 to -0.24). All epigenetic age measures were associated with worse baseline EF (DunedinPACE: β = -0.040, 95% CI [-0.067 to -0.012], padj = 0.01; PCPhenoAge: β = -0.036, 95% CI [-0.062 to -0.011], padj = 0.01; PCGrimAge: β = -0.049, 95% CI [-0.080 to -0.018], padj = 0.01). PCPhenoAge also was associated with worse baseline memory (β = -0.034, 95% CI [-0.058 to -0.010], padj = 0.01) and language (β = -0.032, 95% CI [-0.058 to -0.006], padj = 0.03). DunedinPACE was associated with time to MCI (hazard ratio [HR] = 1.16, 95% CI [1.04-1.30], padj = 0.04) and all-cause dementia (HR = 1.30, 95% CI [1.10-1.54], padj = 0.03). Epigenetic age measures were not associated with the rate of decline. Magnitudes of association for epigenetic age measures remained similar after adjustment for TCBV and t-tau. TCBV and t-tau had similar magnitudes of association in analyses stratified by median epigenetic age.

DISCUSSION: Independent of t-tau and TCBV, epigenetic age measures were associated with time to MCI, AD, and all-cause dementia and baseline cognition, but not with cognitive trajectories. The results support epigenetic age measures as markers of resilience through brain reserve. The findings may have important implications regarding use of epigenetic age measures as biomarkers to track the success of interventions targeting resilience.},
}

@article {pmid42828458,
year = {2026},
author = {Megari, K and Keramida, MM},
title = {Indications and pathways of Type 2 diabetes mellitus as a predictor of neurocognitive decline and dementia: Clinical implications and management.},
journal = {Applied neuropsychology. Adult},
volume = {},
number = {},
pages = {1-11},
doi = {10.1080/23279095.2026.2741894},
pmid = {42828458},
issn = {2327-9109},
abstract = {Type 2 diabetes mellitus (T2DM) is a metabolic disease, one of the most common chronic conditions globally. Studies suggest that T2DM can increase the risk of mild cognitive impairment (MCI), Alzheimer's disease (AD) and other types of dementia; T2DM has been associated with decline in memory, verbal fluency, executive function and processing speed. It seems that T2DM and AD share common biological mechanisms. Multiple studies have investigated them, suggesting that insulin resistance, hyperglycemia and neuroinflammation are some potential factors which can increase risk of dementia in patients with T2DM. Thus, it is suggested that cognitive screening in the early stages of T2DM can be beneficial to prognose disease progression. Despite the current data regarding T2DM and dementia, there is a research gap on interventions focusing on the cognitive and psychological aspects of diabetes. Therefore, future studies should focus on creating tailored interventions for diabetic patients and identify possible biomarkers for the early prediction of cognitive deficits on T2DM. With a deeper understanding, researchers can help prevent or delay cognitive impairment in patients with T2DM contributing to patient's quality of life and the broader landscape of public health.},
}

@article {pmid42828470,
year = {2026},
author = {Sabahizadeh, A and Askarinejad, A and Ahmadzadeh, K and Mirjalili, SR and Farshid, K and Serio, L and Tartaglia, E and Proietti, R and Davies, R and Lip, GYH},
title = {Delirium in Patients With Traumatic Brain Injury and Long-Term Cognitive Decline: A Global Federated Real World Data Analysis.},
journal = {European journal of clinical investigation},
volume = {56},
number = {10},
pages = {e70262},
pmid = {42828470},
issn = {1365-2362},
mesh = {Humans ; Female ; *Brain Injuries, Traumatic/epidemiology/complications ; *Delirium/epidemiology/etiology ; Aged ; Retrospective Studies ; Male ; Middle Aged ; *Cognitive Dysfunction/epidemiology/etiology ; Alzheimer Disease/epidemiology ; Adult ; *Dementia/epidemiology ; Dementia, Vascular/epidemiology ; Aged, 80 and over ; Propensity Score ; },
abstract = {BACKGROUND AND OBJECTIVE: Delirium may occur in patients with traumatic brain injury (TBI), but this may be a marker for subsequent cognitive decline post-TBI. We aimed to compare cognitive outcomes and all-cause mortality between TBI patients with and without delirium.

METHODS: We conducted a retrospective cohort study using the TriNetX global federated research network. We compared TBI patients who developed delirium within 14 days of TBI diagnosis with those who did not. The primary outcome was the 2-year composite risk of dementia, vascular dementia and Alzheimer's disease. Secondary outcomes included dementia, vascular dementia, Alzheimer's disease and all-cause mortality. Pre-specified subgroup analyses were performed in female patients, older adults (≥ 75 years), and individuals with substance use.

RESULTS: TBI patients with delirium (n = 2564; mean age, 66.6 ± 19.4 years; 59.4% male), when compared with TBI patients without delirium (n = 667,950; mean age, 48.0 ± 25.1 years; 60.3% male), had more baseline comorbidities, including psychiatric disease, cerebrovascular disease and ischemic heart disease. After propensity score matching, TBI patients with delirium, compared with those without delirium, had a higher 2-year risk of the primary composite outcome (HR, 2.47; 95% CI, 1.84-3.31), as well as dementia (HR, 2.63; 95% CI, 1.92-3.60), vascular dementia (HR, 2.76; 95% CI, 1.45-5.24) and Alzheimer's disease (HR, 2.23; 95% CI, 1.21-4.09).

CONCLUSION: Delirium following TBI is associated with an increased risk of dementia and Alzheimer's disease. Delirium post-TBI may be a marker or a contributing factor to long-term cognitive decline in TBI patients.},
}

Humans
Female
*Brain Injuries, Traumatic/epidemiology/complications
*Delirium/epidemiology/etiology
Aged
Retrospective Studies
Male
Middle Aged
*Cognitive Dysfunction/epidemiology/etiology
Alzheimer Disease/epidemiology
Adult
*Dementia/epidemiology
Dementia, Vascular/epidemiology
Aged, 80 and over
Propensity Score

@article {pmid42828479,
year = {2026},
author = {Riga, MS and Pérez-Fernández, M and Andrade-Talavera, Y and Domínguez-Velasco, B and Rodríguez-Moreno, A and Álvarez-Dolado, M},
title = {Scn1a-mediated developmental regulation of prefrontal cortex plasticity and cognition.},
journal = {Epilepsia},
volume = {},
number = {},
pages = {},
doi = {10.1002/epi.70484},
pmid = {42828479},
issn = {1528-1167},
support = {//Asociación Apoyo Dravet/ ; RH-0048-2020//Ministry of Health and Consumer of the Andalusian Government/ ; PID2021-127044OB-I00//Ministerio de Ciencia y Universidades/Agencia Estatal de investigacion/Fondos Europeos de Desarrollo Regional (MCIU/AEI/FEDER), UE/ ; PID2022-136597NB-I00//Ministerio de Ciencia y Universidades/Agencia Estatal de investigacion/Fondos Europeos de Desarrollo Regional (MCIU/AEI/FEDER), UE/ ; PID2024-162613OB-I00//Ministerio de Ciencia y Universidades/Agencia Estatal de investigacion/Fondos Europeos de Desarrollo Regional (MCIU/AEI/FEDER), UE/ ; GA_10106117//Skłodowska-Curie Fellowship/ ; },
abstract = {OBJECTIVE: The voltage-gated sodium channel Nav1.1, encoded by Scn1a, is essential for γ-aminobutyric acid (GABA)ergic function, and its alteration is associated with neurological disorders such as Dravet syndrome and Alzheimer's disease. We previously demonstrated that local Nav1.1 dysfunction in the medial prefrontal cortex (mPFC) during adolescence causes epilepsy, cognitive deficits, and depressive-like behaviors. Here, to investigate putative developmental differences, we analyzed whether Nav1.1 dysfunction in the adult mPFC produces comparable phenotypic outcomes.

METHODS: Nav1.1 dysfunction was selectively induced in the adult mPFC via conditional expression of a mutant human SCN1A variant. We then analyzed PFC-related cognitive tasks and depressive-like behaviors; epileptic and oscillatory activity using in vivo electroencephalography (EEG) recordings; and ex vivo synaptic plasticity in mPFC circuits.

RESULTS: As observed after adolescent Nav1.1 dysfunction, adult manipulation induced epileptic activity and depressive-like phenotypes. However, mPFC-dependent cognitive functions remained intact, unlike adolescent mice, which showed impaired working memory and fear extinction. Electrophysiological recordings revealed distinct mPFC oscillatory patterns. Adult Nav1.1 dysfunction reduced sleep-related delta mPFC power and dorsal hippocampus (dHPC)-mPFC coherence, mimicking adolescent patterns. In contrast, no alteration in mPFC oscillatory activity was observed during wakefulness, differing from adolescent mice. IN addition, synaptic plasticity analyses showed that adolescent-but not adult-Nav1.1 dysfunction impaired long-term potentiation (LTP) at cortical L2/3-L2/3 prelimbic synapses. Moreover, LTP was sensitive to Nav1.1 pharmacological activation only in adolescent mice.

SIGNIFICANCE: These findings reveal a developmental role for Nav1.1 activity in mPFC plasticity and cognition, whereas in adulthood, it remains critical for regulating network stability and depressive-like behaviors.},
}

@article {pmid42828568,
year = {2026},
author = {Bernetti, C and Calandrelli, R and Pilato, F and Di Lazzaro, V and Zobel, BB and D'Amelio, M and Mallio, CA},
title = {Exploring the role of glymphatic system in Alzheimer's disease with insights from MRI-based studies: a systematic review.},
journal = {Neuroradiology},
volume = {},
number = {},
pages = {},
pmid = {42828568},
issn = {1432-1920},
abstract = {BACKGROUND: The glymphatic constitutes a crucial neurophysiological mechanism for the clearance of interstitial solutes and neurotoxic metabolites from the central nervous system. Dysfunction within this pathway is increasingly implicated in the etiopathogenesis of neurodegenerative diseases, notably Alzheimer's disease (AD). Advanced magnetic resonance imaging (MRI) modalities, such as diffusion tensor image analysis along the perivascular space (DTI-ALPS), have emerged as non-invasive, in vivo approaches quantifying glymphatic transport efficacy and its association with cognitive decline and AD progression.

METHODS: This systematic review was conducted in adherence with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. and systematic literature retrieval was executed across PubMed, Cochrane, and Scopus databases, targeting studies that employed MRI-based metrics to assess glymphatic functionality in the context of AD.

RESULTS: A total of 35 studies fulfilled the inclusion criteria. AD patients exhibited significantly reduced DTI-ALPS indices, correlating with elevated enlarged perivascular space (ePVS) volumes, neurocognitive deterioration, and cerebral atrophy. Notably ePVSs enlargement emerged as a surrogate marker of glymphatic dysfunction and a predictor of MCI-to-AD conversion. However, amyloid PET correlations exhibited inter-study heterogeneity.

CONCLUSIONS: MRI derived biomarkers, particularly DTI-ALPS index and ePVSs analysis, demonstrate high potential as surrogate indicators of glymphatic impairment in AD. These findings underscore their diagnostic and prognostic value, warranting harmonization of imaging protocols and longitudinal investigations to establish their translational utility in clinical biomarker frameworks.

CLINICAL RELEVANCE STATEMENT: MRI biomarkers of glymphatic dysfunction provide valuable insights into Alzheimer's disease pathophysiology and progression. These imaging markers may enhance early diagnosis, monitor disease progression, and evaluate treatment efficacy in AD.},
}

@article {pmid42828605,
year = {2026},
author = {Przywara, D and Petniak, A and Gil-Kulik, P},
title = {The Therapeutic Potential of MicroRNAs Delivered By Mesenchymal Stem Cells in Parkinson's Disease, Alzheimer's Disease, and Stroke: A Systematic Review of Preclinical Studies.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {42828605},
issn = {1559-1182},
mesh = {*MicroRNAs/administration & dosage/genetics/therapeutic use ; Animals ; Humans ; *Alzheimer Disease/therapy/genetics ; *Stroke/therapy/genetics ; *Mesenchymal Stem Cells/metabolism ; *Mesenchymal Stem Cell Transplantation/methods ; *Parkinson Disease/therapy/genetics ; },
abstract = {Population aging has led to a substantial increase in the prevalence of neurological disorders, including Parkinson's disease (PD), Alzheimer's disease (AD), and stroke. As current therapeutic strategies are largely limited to symptomatic management, the identification of disease-modifying treatments remains a major unmet clinical need. Mesenchymal stem cells (MSCs) and MSCs-derived microRNAs (miRNAs) have emerged as promising therapeutic candidates for these conditions. A systematic literature search was conducted in the PubMed and Scopus databases in accordance with the PRISMA guidelines. The aim was to synthesize the available evidence regarding the effects of MSCs-derived miRNAs on cellular processes, including apoptosis, proliferation, inflammation, oxidative stress, and motor function in experimental models of PD, AD, and stroke. Risk of bias was assessed using the SYRCLE Risk of Bias tool for animal intervention studies and the modified OHAT Risk of Bias Rating Tool (mOHAT). A total of 37 preclinical studies were included in the review: 9 focused on PD, 10 on AD, and 18 on stroke. The synthesized evidence indicates that specific MSCs-derived miRNAs, particularly miR-133b, miR-146a, miR-17-92, and miR-223, exert significant neuroprotective effects. These miRNAs actively modulate gene expression, attenuate neuroinflammation and apoptosis, and reduce the accumulation of disease-specific pathological markers, including α-synuclein and amyloid-β (Aβ). Furthermore, targeted delivery of these miRNAs was associated with improved motor and cognitive outcomes across the evaluated animal models. MSCs-derived miRNAs demonstrate considerable therapeutic potential for the treatment of neurodegenerative diseases and stroke through the modulation of multiple pathological pathways. However, as the current evidence is derived exclusively from in vitro and animal studies, future research should focus on the development of safe, standardized, and reproducible protocols to facilitate the translation of these findings into human clinical trials. The review was registered in the Open Science Framework (OSF): https://osf.io/cxt9b .},
}

*MicroRNAs/administration & dosage/genetics/therapeutic use
Animals
Humans
*Alzheimer Disease/therapy/genetics
*Stroke/therapy/genetics
*Mesenchymal Stem Cells/metabolism
*Mesenchymal Stem Cell Transplantation/methods
*Parkinson Disease/therapy/genetics

@article {pmid42828660,
year = {2026},
author = {Dhapola, R and Kumari, S and Sharma, P and Paidlewar, M and Vellingiri, B and Cho, SG and Dayem, AA and Medhi, B and HariKrishnaReddy, D},
title = {Stem cells and derived growth factors in Alzheimer's disease: mechanistic insights and translational perspectives.},
journal = {Inflammopharmacology},
volume = {},
number = {},
pages = {},
pmid = {42828660},
issn = {1568-5608},
abstract = {Alzheimer's disease (AD) is a significant healthcare concern due to the complex interactions between amyloid-β accumulation, tau pathology, neuroinflammation, synaptic dysfunction, and progressive neuronal death. Stem-cell-based therapies have demonstrated potential to treat this complex condition through immunomodulation, trophic support, and neuroregeneration. Beyond direct cell replacement, stem-cell-derived growth factors have important therapeutic functions by providing strong neurotrophic and cytoprotective effects. These bioactive compounds improve neuronal survival, restore synaptic plasticity, and reduce inflammatory cascades that accelerate the course of AD. Important growth factors that support increased neural resilience, cholinergic preservation, synaptic strengthening, and mitochondrial stabilization include BDNF, NGF, and IGF-1. The current study synthesizes molecular knowledge and new clinical data to assess the translational potential of stem cells and their growth-factor secretome. According to preclinical research, neural stem cells (NSCs) increase synaptic density and maintain cholinergic integrity in APP/PS1 mice, while mesenchymal stem cells (MSCs) lower amyloid burden, inhibit microglial activation, and improve memory. The stem-cell secretome offers a significant therapeutic benefit. BDNF increases synaptic plasticity, NGF promotes cholinergic survival, and IGF-1 improves mitochondrial function and diminishes oxidative stress and tau-mediated toxicity. However, significant obstacles impede clinical advancement. Therapeutic stability is limited by the risks of tumorigenicity, poor long-term engraftment, immunological rejection, and irregular blood-brain barrier penetration. Major challenges persist, such as manufacturing inconsistency, scalability limitations, and difficulties attaining controlled growth-factor dosing. To advance stem-cell-based techniques for significant AD alterations, these hurdles must be overcome by biomaterial optimization, modified secretomes, and standardized production platforms.},
}

@article {pmid42828662,
year = {2026},
author = {Shokr, MM and Abdelaziz, AM},
title = {The immunoproteasome in Alzheimer's disease: a dual regulator of tau pathology and microglial senescence.},
journal = {Inflammopharmacology},
volume = {},
number = {},
pages = {},
pmid = {42828662},
issn = {1568-5608},
abstract = {Alzheimer's disease (AD) is characterized by progressive cognitive decline driven by the convergence of tauopathy, impaired proteostasis, and chronic neuroinflammation. Emerging evidence identifies the immunoproteasome (iP), particularly the β5i/LMP7 subunit, as a central regulator linking these pathological processes. Unlike the constitutive proteasome, the iP is markedly induced in microglia, neurons, and astrocytes under inflammatory conditions through interferon-γ and NF-κB signaling. This review discusses the dual and context-dependent role of the iP in AD pathogenesis. In microglia, chronic iP activation promotes degradation of NRF2, leading to oxidative stress, NLRP3 inflammasome activation, and the development of a senescence-associated secretory phenotype that exacerbates neuroinflammation and tau propagation. In neurons, moderate iP activity facilitates the clearance of phosphorylated tau; however, sustained overactivation generates aggregation-prone tau fragments that enhance trans-synaptic tau spreading. We further highlight the cross-talk between the iP and autophagy pathways through TFEB and p62/SQSTM1 signaling and discuss how gut microbiota-derived inflammatory mediators may prime central iP activation through the gut-brain axis. Importantly, recent preclinical studies support the concept of partial immunoproteasome modulation rather than complete inhibition, with selective LMP7 targeting restoring proteostatic balance, reducing microglial senescence, and attenuating tau pathology. Collectively, the iP emerges as a promising immunopharmacological target and a potential therapeutic rheostat in AD.},
}

@article {pmid42828668,
year = {2026},
author = {Hyun, M and Park, Y and Park, SY and Kim, KW},
title = {Sensory gamma entrainment in older adults with or without cognitive impairment: a systematic review and exploratory meta-analysis.},
journal = {GeroScience},
volume = {},
number = {},
pages = {},
pmid = {42828668},
issn = {2509-2723},
support = {RS-2020-KH095941//Korea Dementia Research Center/ ; RS-2025-02223212//Korea Health Industry Development Institute/ ; },
abstract = {Gamma entrainment using sensory stimulation (GENUS) is a noninvasive approach under investigation in older adults with and without cognitive impairment, including Alzheimer's disease; however, human evidence remains scattered across structural, functional, biomarker, electrophysiological, and cognitive domains. We searched PubMed, Embase, Scopus, and Web of Science for English-language articles published from January 2016 to December 2025, following PRISMA 2020 guidelines and a retrospectively registered PROSPERO protocol. Eligible studies evaluated non-invasive sensory gamma-frequency stimulation in adults aged ≥ 60 years, including Alzheimer's disease-spectrum and cognitively normal older adults, with quantitative outcomes reported in at least one relevant domain. Narrative synthesis was the primary approach, supplemented by an exploratory random-effects meta-analysis of hippocampal and ventricular volume change. Eight studies were included, spanning single-session to 6-month interventions. Findings were directionally favorable across domains but derived from small, heterogeneous studies with nonoverlapping outcomes. Fluid biomarker evidence was limited to exploratory immune-related findings from a single uncontrolled study. Controlled structural studies suggested possible attenuation of hippocampal atrophy, ventricular enlargement, and white matter decline. Functional connectivity findings suggested possible preservation of connectivity in Alzheimer's disease-relevant networks. Electroencephalography studies supported target engagement, with entrainment strength and propagation varying according to stimulation parameters and individual characteristics. Cognitive findings from small exploratory studies did not establish a consistent benefit. Exploratory pooled effects for ventricular and hippocampal volume change were favorable but not robust to conservative sensitivity analysis. Human evidence for GENUS is promising but preliminary and hypothesis-generating; larger, adequately powered, standardized trials are needed before firm efficacy conclusions can be drawn.},
}

@article {pmid42828695,
year = {2026},
author = {Inui, Y and Takechi, H and Watanabe, H and Kato, T and Ito, K and Kobayashi, R and Toyama, H and Inoue, M},
title = {Multimodal neuroimaging in dementia and neurodegenerative disorders: complementary roles of clinically available nuclear medicine and MRI in the era of disease-modifying therapies.},
journal = {Japanese journal of radiology},
volume = {},
number = {},
pages = {},
pmid = {42828695},
issn = {1867-108X},
abstract = {The introduction of anti-amyloid-β antibody therapies has fundamentally changed the clinical landscape of dementia, shifting the role of neuroimaging from diagnosis toward therapeutic decision-making. Amyloid positron emission tomography (PET) has become essential for confirming amyloid pathology and determining treatment eligibility. However, amyloid deposition is frequently observed in cognitively normal elderly individuals and in non-Alzheimer neurodegenerative disorders, indicating that amyloid status alone is insufficient to explain clinical symptoms. In this context, imaging modalities reflecting neurodegeneration, including structural magnetic resonance imaging (MRI) and functional imaging such as [18]F-FDG-PET and brain perfusion single-photon emission computed tomography (SPECT), remain important for assessing disease severity and functional impairment. Furthermore, discrepancies between imaging biomarkers-such as the presence of neurodegeneration without amyloid pathology in cases clinically suspected of Alzheimer's disease, and atypical imaging patterns-are commonly encountered in clinical practice and may reflect underlying pathological heterogeneity. A multimodal imaging approach that integrates multiple biomarkers provides complementary information and may improve diagnostic accuracy and clinical interpretation. In addition, other imaging modalities, including dopamine transporter (DAT) imaging and cardiac sympathetic imaging, can contribute to the evaluation of non-Alzheimer pathologies. This review summarizes the current roles of clinically available multimodal imaging in dementia, with a focus on nuclear medicine and MRI, highlighting their complementary value and clinical implications in the era of disease-modifying therapies.},
}

@article {pmid42828701,
year = {2026},
author = {Lei, Y and Luo, Y and Li, L},
title = {Collagen Triple Helix Repeat Containing 1 (CTHRC1) in the Nervous System: Expression, Signaling Mechanisms, and Functional Implications.},
journal = {Journal of molecular neuroscience : MN},
volume = {76},
number = {4},
pages = {},
pmid = {42828701},
issn = {1559-1166},
support = {2024AAC03777//Natural Science Foundation of Ningxia Province/ ; },
mesh = {Animals ; Humans ; *Extracellular Matrix Proteins/metabolism/genetics ; *Signal Transduction ; },
abstract = {Collagen triple helix repeat containing 1 (CTHRC1) is a secreted extracellular matrix (ECM)-associated protein involved in tissue remodeling, fibrosis, and cancer, but its functions in the nervous system remain incompletely defined. Evidence from peripheral nerve, brain tumor, neurodegeneration, and regeneration models suggests that CTHRC1 may exert context-dependent effects across neural and stromal cell populations. In Schwann cells, CTHRC1 regulates proliferation, migration, and the timing of myelination, whereas in glioma it promotes invasive behavior and treatment-resistant phenotypes. Human cortical proteomics, mouse-model studies, systems genetics, and a neuronal cell model associate CTHRC1 with Alzheimer's disease-related phenotypes, although bulk tissue does not identify the cellular source and a small cerebrospinal fluid cohort showed no significant change. Temporally resolved single-cell analysis in zebrafish identified a transient cthrc1a-expressing fibroblast state required for coordinated inflammatory dynamics during regeneration; an equivalent mammalian mechanism has not been established. Evidence connecting CTHRC1 to synaptic regulation, neuroprotection, Parkinson's disease, and cerebrovascular repair is still preliminary. Wnt, TGF-β/Smad, PI3K/AKT, and MAPK/ERK pathways provide candidate mechanisms, but many were characterized outside normal neural cells. This review critically evaluates the evidence by model and cell type and discusses biomarker and therapeutic prospects, including delivery, specificity, and safety constraints.},
}

Animals
Humans
*Extracellular Matrix Proteins/metabolism/genetics
*Signal Transduction

@article {pmid42828971,
year = {2026},
author = {Cuma, C and Çeşme, M and Borkoev, B and Salieva, K and Tümer, F},
title = {Mechanistic exploration of 4-bromobenzyloxy-1,2,3-triazole derivatives as dual cholinesterase inhibitors: Kinetic, molecular dynamics, and halogen-contact insights.},
journal = {Computational biology and chemistry},
volume = {126},
number = {Pt 1},
pages = {109459},
doi = {10.1016/j.compbiolchem.2026.109459},
pmid = {42828971},
issn = {1476-928X},
abstract = {Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) regulate cholinergic neurotransmission, and their partial inhibition is an established symptomatic strategy in Alzheimer's disease; clarifying how individual ligands engage these enzymes is therefore central to inhibitor design. To probe these cholinesterase-ligand interaction mechanisms, a series of eight 4-bromobenzyloxy-1,2,3-triazole derivatives (10a-10 h) was synthesized and evaluated as AChE and BChE inhibitors. All compounds displayed concentration-dependent inhibition of both enzymes at micromolar concentrations (IC50 = 1.52-4.05 µM for AChE and 2.18-7.83 µM for BChE). Compound 10e was the most effective AChE inhibitor and compound 10 g the most effective BChE inhibitor. Detailed kinetic analysis, with inhibition constants obtained by global nonlinear regression and the mechanism assigned by Akaike-based model selection, revealed predominantly mixed-type inhibition (Ki = 0.95 µM, α = 2.10 for 10e-AChE; Ki = 1.55 µM, α = 2.14 for 10g-BChE) and predominantly noncompetitive inhibition for 10d, indicating simultaneous or allosteric engagement of the catalytic and peripheral sites. These mechanisms were corroborated by molecular docking, 100 ns molecular dynamics simulations, and MM/GBSA analysis, and the docking binding energies correlated closely with experimental potency across the series (r[2] > 0.99). Geometric analysis showed that 10 g engages the BChE gorge through an additional short, non-linear C-F···O contact rather than a classical halogen bond. In silico DFT, ADMET, and toxicity predictions indicated generally drug-like, CNS-penetrant profiles for most derivatives, although 10d was flagged for potential genotoxic liability and deprioritized. Collectively, these findings characterize the dual cholinesterase inhibitory activity of the 4-bromobenzyloxy-1,2,3-triazole scaffold and position 10e and 10 g as effective lead-like compounds warranting further optimization.},
}

@article {pmid42828976,
year = {2026},
author = {Soltani, I and Bahia, W and Slaymi, C and Khemissi, W and Rahali, N and Bougatef, H and Baazaoui, N and Ferchichi, S and Almawi, WY},
title = {Systems-level bioinformatics analysis of hsa-miR-132-3p targets identifies a conserved neuroimmune regulatory module relevant to Alzheimer's disease.},
journal = {Computational biology and chemistry},
volume = {126},
number = {Pt 1},
pages = {109445},
doi = {10.1016/j.compbiolchem.2026.109445},
pmid = {42828976},
issn = {1476-928X},
abstract = {Alzheimer's disease (AD) arises from converging neurodegeneration and neuroinflammation, yet post-transcriptional mechanisms linking these processes remain poorly defined. Hsa-miR-132-3p, a neuron-enriched microRNA consistently downregulated in AD, has emerged as a candidate integrator of synaptic plasticity and innate immune signaling. Targets of hsa-miR-132-3p were collected from five repositories (miRTarBase v10.0, DIANA-TarBase v9.0, ENCORI v3.0, miRWalk v3.0, miRDB v6.0) and integrated using multiMiR. Functional annotation used ShinyGO v0.81 (KEGG, GO-BP), with immune enrichment via MSigDB Hallmark, ImmPort, and InnateDB. High-confidence targets were defined by overlap with TargetScan conserved predictions and MalaCards AD genes. PPI networks were built with STRING v12.0/MCODE, and transcriptomic validation used GSE5281 hippocampal microarray data. Integration of five repositories identified 5429 non-redundant candidate targets, with significant enrichment in prefrontal cortex and CD33 + myeloid cell signatures (adjusted p < 0.05). Immune analyses highlighted TNFα/NF-κB, IL-6/JAK-STAT3, and interferon signaling overrepresentation. Intersection with TargetScan conserved predictions and MalaCards prioritized a 14-gene module (GSK3B, MAPK1, MAPK3, EP300, FOXO3, PIK3CA, PPP3CA, MAPT, EGR1, NR4A2, SLC30A6, ADCYAP1, SLC6A3, SV2A) defined by the convergence of experimentally supported target annotations, conserved TargetScan predictions, and AD-associated gene annotations. PPI mapping identified MAPK1, MAPK3, EP300, MAPT, and EGR1 as a central interaction module associated with inflammatory signaling and tau-associated processes. Hippocampal transcriptomic analysis provided exploratory evidence of overlap between candidate hsa-miR-132-3p targets and AD-associated differentially expressed genes (KDM4B,CBX3 and MORF4L2). This analysis nominates hsa-miR-132-3p as a candidate post-transcriptional regulator potentially linking neuronal stress, tau pathology, and innate immune signaling in AD. The 14-gene module provides a hypothesis-generating framework for cell-type-resolved experimental validation.},
}

@article {pmid42828991,
year = {2026},
author = {Kim, D and Moon, HY and Lee, M},
title = {Exercise, Glucose and Lactate Metabolism in Mild Cognitive Impairment: A Narrative Review.},
journal = {International journal of sports medicine},
volume = {},
number = {},
pages = {},
doi = {10.1055/a-2972-5240},
pmid = {42828991},
issn = {1439-3964},
abstract = {Mild cognitive impairment (MCI) is associated with cerebral glucose hypometabolism and an increased risk of progression to Alzheimer's disease (AD). Altered lactate metabolism may represent an additional component of this metabolic vulnerability. We propose the Dual-Fuel Hypothesis as a testable framework linking glucose-related metabolism with lactate-dependent energy and signaling pathways, while recognizing that this pathway has not been directly tested in MCI. This narrative review was guided by the SANRA framework. Structured screening was conducted specifically for randomized exercise-intervention studies in MCI, identifying 35 publications representing 29 independent cohorts. Evidence consistently supports impaired cerebral glucose metabolism in MCI due to AD, whereas alterations in lactate homeostasis and transport remain less clearly defined. Exercise improves systemic glucose utilization and increases circulating lactate, particularly during vigorous intensity aerobic and resistance exercise. Several trials reported favorable cognitive or neuroimaging outcomes, although larger or longer trials did not consistently show significant between-group cognitive benefits. No identified MCI exercise trial has concurrently measured exercise-induced lactate, cerebral substrate utilization, and cognition.},
}

@article {pmid42829013,
year = {2026},
author = {Chen, H and He, Y and Hou, L and Liu, L and Ma, C and , },
title = {A statistical framework for integrative imaging genomics with biclustering and ensemble penalized regression in Alzheimer's disease.},
journal = {NeuroImage},
volume = {},
number = {},
pages = {122267},
doi = {10.1016/j.neuroimage.2026.122267},
pmid = {42829013},
issn = {1095-9572},
abstract = {Imaging genomics provides a powerful paradigm for decoding the complex interplay between molecular variation and brain functional phenotypes in neurodegenerative disorders. In this study, the molecular modality is specifically gene expression data rather than time-invariant genetic variants. However, statistically integrating these high-dimensional modalities remains challenging, as existing methods often rely on incomplete biological priors or overlook the latent modular structure of the data. To address this, we propose BRIDGE (Biclustering and ensemble penalized Regression for Integrative Data in Genomics and nEuroimaging), a unified statistical framework that synergistically integrates biclustering with ensemble penalized regression. Our approach proceeds in three interdependent stages: (1) accurate estimation of individual brain functional networks via sparse precision matrices; (2) data-driven discovery of regulatory modules-defined as subsets of gene expression features co-varying with subsets of brain connections-using a sparse biclustering algorithm; and (3) stable disease classification and biomarker identification via dimensionality reduction integrated with an ensemble penalized logistic regression model. Simulation studies demonstrate that BRIDGE outperforms ablation variants of the proposed framework and external competing benchmark methods in both feature selection performance and classification accuracy. In an application to the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort, the framework achieved robust out-of-sample classification performance and uncovered biologically interpretable disease-related modules. These results highlight BRIDGE as a rigorous tool for integrative imaging genomics, capable of identifying pathogenic factors without reliance on a priori knowledge.},
}

@article {pmid42829100,
year = {2026},
author = {Stepanyan, H and Ghorbani, H and Poghosyan, M and Danielyan, M and Minasyan, A and Hunanyan, A and Hunanyan, N},
title = {Therapeutic potential of proline-rich peptide-1 (PRP-1) in counteracting amyloid-β-mediated cortical and hippocampal neurodegeneration in a rat model.},
journal = {Neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neuroscience.2026.09.043},
pmid = {42829100},
issn = {1873-7544},
abstract = {Alzheimer's disease (AD) is associated with amyloid β (Aβ) accumulation, neuronal metabolic dysfunction, and structural degeneration. This study compares the neurotoxic effects of Aβ25-35 and Aβ1-42 in the rat cerebral cortex and hippocampus and evaluates the neuroprotective potential of proline rich peptide 1 (PRP-1). Amyloid peptides were administered bilaterally into the lateral ventricles, followed by intramuscular PRP-1 at 0.1 mg/kg once daily for three weeks, beginning 24 h after amyloid administration. Neuronal metabolic activity was assessed by Ca2[+] dependent acid phosphatase histochemistry with a lead capture reaction. Reaction intensity was quantified by densitometry as mean gray value (MGV), with lower values indicating greater reaction product accumulation and higher enzymatic activity. Both amyloid species disrupted cortical laminar organisation and altered enzymatic reactivity in the perikarya and dendrites of cortical pyramidal neurons, with Aβ1-42 causing greater structural disruption. When fields recorded with the same objective were compared, Aβ1-42 produced suppression of enzymatic activity in the hippocampus. CA1 pyramidal neurons showed the highest susceptibility, with confluent areas of reduced reactivity and interruption of the pyramidal cell layer. In the cortex, changes were restricted to the most severely damaged neurons. PRP-1 attenuated these alterations, preserved neuronal morphology, increased the number of reactive neurons, and enhanced enzymatic reactivity in both regions. Protection was greater in the hippocampus. These findings indicate that Aβ1-42 has greater neurotoxicity than Aβ25-35 and that PRP-1 reduces amyloid associated neuronal injury while supporting metabolic and structural recovery. PRP-1 merits further investigation as a candidate therapeutic agent for early amyloid associated neurodegeneration.},
}

@article {pmid42829399,
year = {2026},
author = {Tang, H and Fachim, HA and Harte, MK and Reynolds, GP},
title = {Association between BDNF methylation and expression of the NLRP3 inflammasome in the brain is disrupted in Alzheimer's disease.},
journal = {Journal of neural transmission (Vienna, Austria : 1996)},
volume = {},
number = {},
pages = {},
pmid = {42829399},
issn = {1435-1463},
abstract = {Activation of the NLRP3 inflammasome pathway and dysfunction of brain-derived neurotrophic factor (BDNF) are both implicated in the pathogenesis of Alzheimer's disease (AD). While in vitro and in vivo models support these mechanisms, there is little research investigating their relationship in human brain tissue, and whether this relationship may be abnormal in the AD brain. Temporal cortex tissue taken post-mortem from AD patients and control subjects was analysed for expression of genes for the NLRP3 pathway (NLRP3, PYCARD, CASP1), the potassium channel THIK1 (KCNK13), and related pro-inflammatory cytokines (IL-1β, IL-18). BDNF mRNA expression and DNA methylation in the BDNF exon IV promoter were determined. Correlations between these BDNF measures and NLRP3-related genes were investigated. A significant relationship between BDNF mRNA expression and mean methylation was observed in control subjects but not in AD. In controls, significant correlations with both BDNF expression and mean BDNF methylation were observed for NLRP3, CASP1 and IL1B. These correlations were lost in the AD group, which also showed a significant correlation of KCNK13 expression with both BDNF measures, not seen in controls. This study indicates that the relationship between BDNF and NLRP3 activation, as measured by NLRP3 inflammasome components and proinflammatory cytokine products, is disrupted in AD. The contrary correlation emerging in AD between BDNF measures and KCNK13 expression, shown to be elevated in AD, indicates the possible relationship of this finding with BDNF dysfunction. These findings enhance our understanding of AD pathophysiology, demonstrating the importance of understanding the neuroinflammatory-neurotrophic balance in neurodegenerative processes.},
}

@article {pmid42829810,
year = {2026},
author = {Sander, FW and Sallard, É and Silva, M and Schneider, L and Diserens, K and Graf, C and Serino, A and Sokolov, AA},
title = {Precision cognitive neurorehabilitation: dose, adaptivity, digital therapeutics and implementation.},
journal = {Expert review of neurotherapeutics},
volume = {},
number = {},
pages = {1-18},
doi = {10.1080/14737175.2026.2723909},
pmid = {42829810},
issn = {1744-8360},
abstract = {INTRODUCTION: Cognitive deficits are determinants of long-term disability and socio-professional reintegration across neurological disorders, including stroke, traumatic brain injury, multiple sclerosis, and neurodegenerative diseases. Despite evidence supporting cognitive neurorehabilitation, its implementation remains heterogeneous, and therapeutic parameters are insufficiently defined.

AREAS COVERED: The authors reviewed the published literature from PubMed and Google Scholar from 1 January 2015 to 30 June 2026, supplemented by seminal publications. Clinical trials, systematic reviews, meta-analyses, and observational and proof-of-concept studies were prioritized. This brief narrative review examines restorative and compensatory cognitive neurorehabilitation for deficits of attention, executive functions, language and disorders of consciousness in people after stroke and traumatic brain injury (TBI), older adults, and those with neurological and neurodegenerative conditions, including multiple sclerosis, Alzheimer's and Parkinson's disease. Emphasis is placed on dose, frequency, adaptivity, personalization, and digital and technology-assisted interventions. Methodological challenges include heterogeneity of protocols, limited use of active control conditions, insufficient long-term follow-up, and the gap between cognitive test improvements and meaningful effects on participation.

EXPERT OPINION: Advancing cognitive neurorehabilitation requires precision-driven approaches integrating digital therapeutics with clinical frameworks. Large-scale pragmatic trials, meaningful endpoints, and implementation strategies across the continuum of care will be essential to transform cognitive neurorehabilitation into a component of neurological practice.},
}

@article {pmid42830099,
year = {2026},
author = {Serebryanaya, DV and Kolgaeva, KA and Dya, GA and Ermakov, IM and Belousov, VV},
title = {Astrocyte Structure-Function Relationship in Senescence and Neurodegeneration.},
journal = {Biochemistry. Biokhimiia},
volume = {91},
number = {9},
pages = {1522-1549},
doi = {10.1134/S000629792660208X},
pmid = {42830099},
issn = {1608-3040},
mesh = {*Astrocytes/metabolism/pathology/cytology ; Humans ; *Neurodegenerative Diseases/metabolism/pathology ; Animals ; *Cellular Senescence ; *Aging/pathology ; Senescence-Associated Secretory Phenotype ; },
abstract = {Astrocytes play a critical role in maintaining brain homeostasis by providing metabolic support to neurons, regulating neurotransmitter levels, modulating synaptic transmission, and preserving the blood-brain barrier (BBB) integrity. Aging is associated with the accumulation of senescent astrocytes - cells that have lost their ability to grow and divide but remained metabolically active and resistant to apoptosis. In neurodegenerative diseases, astrocytes develop a reactive phenotype. Both senescent and reactive astrocytes are characterized by distinct secretory phenotypes known for the production of pro-inflammatory cytokines, chemokines, and metalloproteinases, that considerably overlap in both states of astrocytes. Recent studies indicate that the number of senescent astrocytes in the brain directly correlates with the development of neurodegenerative diseases. However, the relationship between senescence and neurodegeneration remains poorly understood. This review examines the similarities and differences in the structural and functional features of astrocytes in senescent and pro-inflammatory states, explores potential interactions between them, analyzes intermediate functional states, and discusses potential mechanisms by which astrocytes of both phenotypes contribute to the development of neurodegenerative diseases.},
}

*Astrocytes/metabolism/pathology/cytology
Humans
*Neurodegenerative Diseases/metabolism/pathology
Animals
*Cellular Senescence
*Aging/pathology
Senescence-Associated Secretory Phenotype

@article {pmid42830353,
year = {2026},
author = {Hansen, JS and Pike, ACW and Chi, G and Wolf, G and Tranberg-Jensen, J and Lichtmannegger, H and Speedman, D and Ingles-Prieto, A and Goericke, F and Batoulis, H and Beck, H and Rao, R and Mirshahi, T and Sauer, DB and Superti-Furga, G and Huber, KVM},
title = {High-resolution structures of human NHE6 and NHE9 elucidate endosomal ion and lipid interactions.},
journal = {Nature communications},
volume = {17},
number = {1},
pages = {},
pmid = {42830353},
issn = {2041-1723},
support = {218514/Z/19/Z//Wellcome Trust (Wellcome)/ ; 875510//Innovative Medicines Initiative (IMI)/ ; 777372//Innovative Medicines Initiative (IMI)/ ; NIGMS 147197//Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)/ ; NIGMS 147197//Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)/ ; },
mesh = {Humans ; *Sodium-Hydrogen Exchangers/metabolism/chemistry/genetics/ultrastructure ; *Endosomes/metabolism ; Cryoelectron Microscopy ; Binding Sites ; Sodium/metabolism ; Models, Molecular ; Ion Transport ; },
abstract = {Endosomal NHE6 (SLC9A6) and NHE9 (SLC9A9) transporters are essential for maintaining pH homeostasis within endosomes and their dysfunction has been linked to neurological and neurodegenerative disorders. NHE6 and NHE9 are widely considered to function as electroneutral exchangers that couple the export of protons to the import of sodium or potassium ions across cellular membranes, thereby forming the basis of proton leak pathways for internal pH balancing and fine-tuning. Among the 13 identified SLC9 family members, only NHE6 and NHE9 are targeted to endosomes. Despite their biological importance and therapeutic potential, the structural basis for their activity and regulation remains elusive. Here, we present the cryo-EM structures of human NHE9 and two splice variants of NHE6 that differ by alternative inclusion of the β-hairpin motif-containing loop domain located between transmembrane helices 2 and 3, showcasing structural diversity within the organellar NHE subfamily. By mapping the sodium-binding site, our results provide mechanistic insights into ion transport, and for NHE6 we provide evidence for a conserved PIP2-mediated regulatory mechanism. These findings provide a framework for understanding endosomal NHE function with implications for disorders such as Alzheimer's disease and glioblastoma.},
}

Humans
*Sodium-Hydrogen Exchangers/metabolism/chemistry/genetics/ultrastructure
*Endosomes/metabolism
Cryoelectron Microscopy
Binding Sites
Sodium/metabolism
Models, Molecular
Ion Transport

@article {pmid42830424,
year = {2026},
author = {Chen, Y and Liu, Y and Xie, J and Wang, S and Zhou, D and Song, G and Dou, Y},
title = {A LIFU-responsive phase-change nanoplatform enhances hippocampal galantamine exposure and cognitive outcomes in APP/PS1 mice.},
journal = {Journal of biomaterials science. Polymer edition},
volume = {},
number = {},
pages = {1-23},
doi = {10.1080/09205063.2026.2741654},
pmid = {42830424},
issn = {1568-5624},
abstract = {Alzheimer's disease (AD) lacks spatiotemporally controllable strategies for drug delivery to deep brain targets. Galantamine (GTM) is clinically used for symptomatic management of AD, yet systemic dosing is constrained by peripheral adverse effects and limited, nonselective brain exposure. Here, we engineered a PEGylated phase-change liposomal nanoplatform co-loading GTM and perfluoropentane (PFP) (PEG-LIP@PFP@GTM) to integrate noninvasive nose-to-brain delivery with low-intensity focused ultrasound (LIFU)-assisted enhancement of GTM exposure in the hippocampal region. PEG-LIP@PFP@GTM showed a hydrodynamic diameter of 158.8 ± 1.6 nm with a PDI of 0.165 ± 0.017, an encapsulation efficiency of 69.26 ± 2.07%, and a drug loading content of 6.37 ± 0.65%. PFP endowed the formulation with thermo-responsive phase-transition behavior and LIFU-enhanced GTM release under physiological-temperature conditions. In vivo fluorescence imaging and ex vivo brain sectioning provided evidence of brain accessibility after intranasal administration, while also identifying 4 h post-dosing as a practical window for hippocampal LIFU irradiation. In APP/PS1 mice, compared with the non-irradiated nanoplatform group, phase-change liposomes combined with hippocampal LIFU irradiation significantly increased PSD95 fluorescence intensity (p = 0.0028) and improved Y-maze novel-arm time (p = 0.0003) and Morris water maze target-quadrant time (p = 0.0237), and significantly reduced the Aβ-positive area (p = 0.0461). Histological examination revealed no overt abnormalities in the nasal mucosa or major peripheral organs under the tested conditions. Collectively, these findings support combining intranasal nanocarrier delivery with externally applied hippocampal LIFU, with LIFU activation providing additional benefit beyond non-irradiated nanocarrier treatment under the tested conditions.},
}

@article {pmid42830447,
year = {2026},
author = {Moczygemba, W and Kim, B and Belza, B and Waddington, E and Johnson, S and Fazio, S and Prophater, L},
title = {Implementing Person-Centered Dementia Care Practices Using a Care Community Coaching Intervention.},
journal = {The Gerontologist},
volume = {},
number = {},
pages = {},
doi = {10.1093/geront/gnag224},
pmid = {42830447},
issn = {1758-5341},
abstract = {BACKGROUND AND OBJECTIVES: As person-centeredness is key to quality dementia care, the Care Community Coaching Program (CCCP) was created to implement the 2018 Alzheimer's Association Dementia Care Practice Recommendations (DCPR) in long-term care communities. This paper describes the implementation and preliminary efficacy of the CCCP on adoption of the DCPR for person-centered care (PCC) and workforce practices, and current DCPR implementation in care communities.

RESEARCH DESIGN AND METHODS: Uses a single group, pre- and posttest design drawing on field notes and data collected from 38 communities in a study on the impact of the CCCP in care communities in Ohio. Changes in the implementation of the DCPR for PCC were measured using a paired t test; changes in the DCPR for workforce practices were measured using a Wilcoxon signed-rank test. Additional post-hoc descriptive statistics describe current implementation of the DCPR.

RESULTS: Participating communities saw statistically significant improvements related to the implementation of all but one DCPR for PCC and none related to workforce practices. Pre-intervention implementation rates for the DCPR for PCC and for workforce practices were 61.8% (n = 35 communities), and 78.3% (n = 10 communities), respectively. Exemplar practice changes, and facilitators and barriers to change are additionally described.

DISCUSSION AND IMPLICATIONS: The CCCP can be effectively implemented in care communities and shows preliminary efficacy in increasing the adoption of the DCPR for PCC. Areas for future research on the impact of the CCCP, and implications for improving the person-centeredness of dementia care in care communities, are identified and discussed.},
}

@article {pmid42830517,
year = {2026},
author = {Horie, T and Fujima, N and Kameda, H and Kamishima, T and Kudo, K},
title = {Effects of Artificial Intelligence-based Reconstruction on Image Quality and Voxel-based Morphometry Analysis of Atrophy in Accelerated MPRAGE.},
journal = {Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine},
volume = {25},
number = {4},
pages = {},
doi = {10.2463/mrms.mp.2026-0090},
pmid = {42830517},
issn = {1880-2206},
mesh = {Humans ; *Artificial Intelligence ; *Magnetic Resonance Imaging/methods ; Atrophy/diagnostic imaging ; *Brain/diagnostic imaging/pathology ; Signal-To-Noise Ratio ; Male ; Female ; Adult ; *Imaging, Three-Dimensional/methods ; *Image Processing, Computer-Assisted/methods ; Image Interpretation, Computer-Assisted/methods ; Healthy Volunteers ; Reproducibility of Results ; },
abstract = {PURPOSE: To investigate the effects of artificial intelligence (AI)-based reconstruction on image quality and voxel-based morphometry (VBM)-based atrophy analysis in 3D Magnetization Prepared Rapid Gradient Echo (MPRAGE).

METHODS: Ten healthy volunteers underwent 3T MPRAGE imaging using varying acceleration factors with sensitivity encoding (SENSE) (SE; 2,3), compressed sensing (CS; 2,3,5,8), and AI-based reconstruction (AI; 2,3,5,8). Quantitative assessment included SNR and contrast-to-noise ratio (CNR) in both superficial and deep brain regions. Visual assessment of image quality was performed by 2 experienced neuroradiologists. VBM-based Z-score analysis of regional atrophy was performed using Voxel-based Specific Regional Analysis System for Alzheimer's Disease (VSRAD). Images acquired using a widely recognized standard imaging protocol, SENSE acceleration factor 2 with 1.0-mm isotropic voxels, were used as the reference, and various reconstruction methods and acceleration factors were compared.

RESULTS: Conventional SENSE and CS reconstructions showed stepwise decreases in SNR and CNR with increasing acceleration factors. SNR decrease was particularly pronounced in deep brain regions. Images with AI-based reconstruction maintained relatively stable SNR and CNR across acceleration factors, showing consistent performance in both superficial and deep regions. Visual assessment confirmed reduced noise in images with AI-based reconstruction, which were rated as more favorable for interpretation than SE or CS images. VSRAD analysis demonstrated high correlation with reference images and minimal systematic bias across all acceleration conditions.

CONCLUSION: AI-based reconstruction may enable faster MPRAGE acquisition (up to 5-fold acceleration) while preserving image quality and the reproducibility of VBM-based atrophy analysis.},
}

Humans
*Artificial Intelligence
*Magnetic Resonance Imaging/methods
Atrophy/diagnostic imaging
*Brain/diagnostic imaging/pathology
Signal-To-Noise Ratio
Male
Female
Adult
*Imaging, Three-Dimensional/methods
*Image Processing, Computer-Assisted/methods
Image Interpretation, Computer-Assisted/methods
Healthy Volunteers
Reproducibility of Results

@article {pmid42830961,
year = {2026},
author = {Josephs, KA and Weigand, SD and Satoh, R and Lavrova, A and Tapia, AL and Graff-Radford, J and Machulda, MM and Kantarci, K and Boeve, BF and Petersen, RC and Jack, CR and Dickson, DW and Nguyen, AT and Reichard, RR and Lowe, VJ and Whitwell, JL},
title = {Neurofibrillary tangle deposition in primary idiotypic isocortices using flortaucipir PET in histopathologically confirmed Alzheimer's disease.},
journal = {iScience},
volume = {29},
number = {10},
pages = {117530},
pmid = {42830961},
issn = {2589-0042},
abstract = {Tau deposition in Alzheimer's disease (AD) spreads throughout the brain in a stereotypical pattern captured by the Braak neurofibrillary tangle staging scheme. While involvement of primary isocortex defines the highest stage, it is unclear whether flortaucipir PET uptake differs among primary isocortical regions. We determined relationships between flortaucipir uptake in primary visual, auditory, motor, and somatosensory isocortices and Braak stage in 155 autopsy-confirmed participants with AD. Flortaucipir uptake was observed starting at Braak stage V, with visual and auditory isocortices showing greater and faster increases in uptake than somatosensory and motor; age and APOE ε4 influenced uptake. Flortaucipir uptake and change in primary isocortices were similar in the lateral temporal cortex but different in the entorhinal cortex. Findings suggest that tau deposition in primary isocortices in AD occurs earlier than currently emphasized, although there are differences among them. Given these findings, clinical correlations of primary isocortical involvement in AD need to be evaluated.},
}

@article {pmid42827376,
year = {2026},
author = {Carvalho, LB and Yamada, AK and Furtado, LA and Feltran, GDS and de Lima, ER and Paiva, A and Canineo, D and Bernardi, MM and Fernandes, CJDC and da Silva, RAF},
title = {REST in the Central Nervous System: Context-Dependent Regulation of Neuronal Homeostasis and Disease.},
journal = {International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience},
volume = {86},
number = {6},
pages = {e70186},
doi = {10.1002/jdn.70186},
pmid = {42827376},
issn = {1873-474X},
support = {301498/2022-9//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 88887.827837/2023-00//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; },
mesh = {Humans ; RE1-Silencing Transcription Factor ; *Homeostasis/physiology ; Animals ; *Neurons/metabolism ; *Repressor Proteins/metabolism/genetics ; *Central Nervous System/metabolism ; },
abstract = {The RE1-silencing transcription factor (REST), also known as neuron-restrictive silencer factor (NRSF), is a zinc-finger domain-containing transcriptional regulator involved in coordinating gene expression programmes in the nervous system. Initially characterized as a repressor of neuronal genes in nonneuronal cells, REST also exerts context-dependent functions during neurodevelopment, neuronal maturation, homeostasis and brain ageing. Its activity involves the recruitment of multiple regulatory complexes, including Sin3A/HDACs and CoREST/LSD1, as well as interactions with mechanisms associated with DNA methylation and hydroxymethylation. REST also integrates regulatory networks involving noncoding RNAs. MicroRNAs such as miR-9, miR-124 and miR-132 participate in networks that interact with REST, contributing to the regulation of neuronal differentiation, maturation and function, whereas interactions with long noncoding RNAs remain less well characterized. Alterations in REST expression, subcellular localization or activity have been associated with various neurological and neurodegenerative conditions. In specific neuronal populations during ageing, nuclear REST has been associated with the regulation of genes involved in stress responses and neuronal resilience, whereas alterations in REST activity have been observed in diseases such as Alzheimer's and Huntington's disease. In addition, mechanistic evidence indicates that cellular metabolic state, particularly alterations in glycolysis and the NADH/NAD[+] ratio, may influence REST-regulated pathways. In contrast, associations between REST and factors such as physical exercise and creatine availability remain predominantly indirect or hypothetical. In this review, we synthesize the evidence regarding the transcriptional and epigenetic regulatory mechanisms associated with REST, its interactions with noncoding RNA networks and its functions during neuronal development, homeostasis and ageing. We also discuss the interfaces between REST, metabolism and environmental factors, highlighting differences in the strength of the available evidence, current limitations and mechanistic gaps that warrant further investigation.},
}

Humans
RE1-Silencing Transcription Factor
*Homeostasis/physiology
Animals
*Neurons/metabolism
*Repressor Proteins/metabolism/genetics
*Central Nervous System/metabolism

@article {pmid42827801,
year = {2026},
author = {Bressler, SG and Blacher, C and Harpaz, KA and Grunhaus, D and Rüdiger, SGD and Hurevich, M and Shalev, DE and Miller, Y and Friedler, A},
title = {Site-specific phosphorylation of Ser352 drives aggregation of Tau R4 under acidosis conditions.},
journal = {Chemical science},
volume = {},
number = {},
pages = {},
pmid = {42827801},
issn = {2041-6520},
abstract = {In Alzheimer's disease, neurons undergo acidosis as their pH drops from ∼7.1 to ∼6.5. Here we elucidate the molecular mechanism of specific Tau aggregation only at this lower pH. We show that a specific phosphorylation event in the Tau R4 domain is coupled to this pH drop to drive a defined phase transition from condensates to fibrils. Using a combination of experimental and computational studies, our results demonstrate that site-specific phosphorylation of Ser352 is the molecular switch that induces aggregation of Tau only at the more acidic, disease-related pH. We designed and synthesized a phosphopeptide library covering all phosphorylation patterns of the Tau-R4 domain and tested its response to controlled acidification using an array of complementary biophysical methods. This revealed that only a single phosphorylation of Ser352 led to acid-driven aggregation of Tau-R4. At neutral pH, Tau-R4 with a phosphorylation on Ser352 formed liquid condensates. These condensates converted irreversibly into amyloid filaments as the pH gradually decreased towards the level associated with pathological acidosis. Using a combination of [31]P- and [1]H-NMR, MD simulations and microscopy studies, we show that the mechanism by which the phosphorylation of Ser352 Tau R4 exerts its effects is based on the unique position of this residue within the protein structure. pSer352 is located at the inside of the tip of a β-hairpin, pointing into the hydrophobic core of the amyloid fold. This buried position increases its effective pK a, resulting in compacting of the hairpin following pSer352 protonation upon acidification. This shortens the inter-sheet distance at this position and tightens the filament. We conclude that this single protonation event of the pSer352 phosphate is responsible for the macroscopic phase transition from condensates to aggregates. Our results provide the molecular explanation for the specific aggregation of Tau under the pathologically relevant acidic pH, which is substantially different from its behavior at neutral pH.},
}

@article {pmid42827967,
year = {2026},
author = {Ling, Z and Huang, S and Cheng, Y and Liu, X and Xu, X and Chen, Y and Hu, P and Wu, L and Cai, G},
title = {Short-chain fatty acid-producing commensals: Key modulators of AD neuroinflammation via the microbiota-gut-brain axis.},
journal = {Current research in microbial sciences},
volume = {11},
number = {},
pages = {100660},
pmid = {42827967},
issn = {2666-5174},
abstract = {Alzheimer's disease (AD) lacks effective disease-modifying therapies. Neuroinflammation has emerged as a central driver of AD pathogenesis, and the gut-brain axis represents a key modulator of neuroimmune responses. Short-chain fatty acids (SCFAs), such as acetate, propionate, and butyrate, are microbial metabolites that bridge gut homeostasis with brain function. This review synthesizes current evidence on the functional depletion of SCFA-producing gut bacteria in AD, the journey of SCFAs from the gut to the brain, and their pleiotropic actions on neuroinflammatory cell states. SCFAs regulate microglial and astrocytic phenotypes, suppress NLRP3 inflammasome activation, and promote peripheral immune tolerance via GPCR signaling, HDAC inhibition, and metabolic reprogramming. They also modulate amyloid-β deposition, tau pathology, and synaptic integrity. Translational strategies, including dietary interventions, next-generation probiotics, postbiotics, and fecal microbiota transplantation, are critically evaluated. We further discuss challenges such as causal evidence gaps, host heterogeneity, and stage-dependent therapeutic windows, and propose a pharmacomicrobiomics framework for biomarker-guided trial design. Restoring SCFA-mediated regulatory networks holds promise as a first-line disease-modifying strategy for AD, but clinical translation will require rigorous mechanistic dissection and personalized approaches.},
}

@article {pmid42825390,
year = {2026},
author = {Vanderlip, CR and Hartley, SL and Krinsky-McHale, S and Hom, C and Brickman, AM and Petersen, ME and Head, E and Stark, CEL and , },
title = {Memory and Plasma pTau217 Refine Prognosis in Down Syndrome.},
journal = {Annals of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ana.78366},
pmid = {42825390},
issn = {1531-8249},
abstract = {Individuals with Down syndrome (DS) are at high risk for Alzheimer's disease (AD), yet accessible tools for routine clinical screening of AD in individuals with DS remain limited. Using data from the Alzheimer Biomarker Consortium-Down Syndrome (ABC-DS), we show that integrating plasma pTau217 with performance on the modified cued recall task identifies a subgroup of cognitively stable individuals at markedly elevated risk of developing clinical impairment in the next 7 years. This low-burden, multimodal framework improves prognosis, supports more informed clinical management and efficient trial enrichment in Down syndrome. ANN NEUROL 2026.},
}

@article {pmid42825454,
year = {2026},
author = {Varshney, H and Siddique, YH},
title = {Molecular and genetic basis of alzheimer's disease and emerging treatment Modalities.},
journal = {Neurodegenerative disease management},
volume = {},
number = {},
pages = {1-21},
doi = {10.1080/17582024.2026.2739332},
pmid = {42825454},
issn = {1758-2032},
abstract = {BACKGROUND: Alzheimer's disease (AD) is linked to various causes and pathological processes. It represents a major global health challenge due to its increasing prevalence in aging populations. AD involves multifactorial pathological mechanisms. Two different forms of AD defined by changes in specific genes like APOE4, CLU, TREM2, PICALM, BIN1, MS4A, CR1, ABCA7 and APH1B. Apart from specific genetic mutations, there are multiple risk factors such as aging, obesity, lifestyle, head injury, drinking, smoking and environmental factors that further influence disease risk and its progression.

METHODS: The literature of this review article was taken from different search engines viz. Pubmed, Google Scholar and Scopus, explaining modifiable contributing factors and prognostic markers, including the genetics of AD and overall, this review analyzes literature published between 2000 to 2025 to summarizes the current status of disease, highlighting its importance for improving diagnosis, prognosis, and the development of targeted therapeutic strategies.

RESULT: There are multiple contributing factors in both the disease mechanism and development of AD, apart from amyloid hypothesis and neurofibrillary tangles.

DISCUSSION: A strategic analysis and targeted treatment of these contributing factors could help mitigate the progression of AD and offer potential protective benefits.},
}

@article {pmid42825521,
year = {2026},
author = {Nicol, NI and Li, T and Su, Q and Suhocki, A and Dunlap, E and Zhou, X and Jester, HM and Swift, NA and Underwood, E and Lee, J and Cervera-Juanes, R and Ma, T},
title = {AMPK Activator MK-8722 Improves Spatial Memory Deficit and Alters Metabolome in APP/PS1 AD Mouse Model.},
journal = {Journal of neurochemistry},
volume = {170},
number = {10},
pages = {e70563},
doi = {10.1111/jnc.70563},
pmid = {42825521},
issn = {1471-4159},
support = {R01 AG073823/AG/NIA NIH HHS/United States ; RF1 AG082388/AG/NIA NIH HHS/United States ; },
mesh = {Animals ; *Alzheimer Disease/drug therapy/metabolism/genetics ; *Metabolome/drug effects/physiology ; Mice ; Mice, Transgenic ; *AMP-Activated Protein Kinases/metabolism ; Presenilin-1/genetics ; *Amyloid beta-Protein Precursor/genetics ; *Memory Disorders/drug therapy/metabolism/genetics ; Disease Models, Animal ; Male ; Hippocampus/drug effects/metabolism ; *Spatial Memory/drug effects/physiology ; },
abstract = {Alzheimer's disease (AD) involves early synaptic vulnerability and systemic metabolic dysfunction, yet the impact of peripheral metabolic state on brain function remains unclear. Previous studies indicate a link between AMP-activated protein kinase (AMPK) signaling dysregulation and AD pathophysiology. Here we tested whether systemic treatment of a potent pan-AMPK activator MK-8722 influences cognitive function, synaptic plasticity, and circulating metabolic profiles in APP/PS1 AD model mice at the age of 6-8 months. MK-8722 was well tolerated and activated AMPK in the liver but not in the hippocampus. Our findings revealed that MK-8722 selectively improved AD-associated hippocampal-dependent spatial memory deficits and enhanced dendritic spine maturation in the hippocampus of APP/PS1 mice. In contrast, MK-8722 did not alter hippocampal long-term potentiation (LTP). In-depth analysis of plasma lipidomics and metabolomics revealed coordinated disruptions in glycerophosphatidylcholine species, glutathione cycling, carnitine-dependent fatty acid transport, and the kynurenine pathway in APP/PS1 mice, which were partially normalized by MK-8722 treatment. These findings suggest that peripheral AMPK activation can remodel systemic metabolic networks and improve certain aspects of cognitive and synaptic outcomes in early AD, supporting a model in which metabolic interventions outside the brain influence neuronal resilience.},
}

Animals
*Alzheimer Disease/drug therapy/metabolism/genetics
*Metabolome/drug effects/physiology
Mice
Mice, Transgenic
*AMP-Activated Protein Kinases/metabolism
Presenilin-1/genetics
*Amyloid beta-Protein Precursor/genetics
*Memory Disorders/drug therapy/metabolism/genetics
Disease Models, Animal
Male
Hippocampus/drug effects/metabolism
*Spatial Memory/drug effects/physiology

@article {pmid42825683,
year = {2026},
author = {Shin, J and García, AM and Scimeca, M and Kiran, S and Sung, JE},
title = {Culture-Agnostic and Culture-Specific Analyses of Semantic Fluency in Korean and English Speakers With Alzheimer's Disease.},
journal = {American journal of speech-language pathology},
volume = {},
number = {},
pages = {1-14},
doi = {10.1044/2026_AJSLP-25-00418},
pmid = {42825683},
issn = {1558-9110},
abstract = {PURPOSE: This study investigated cross-linguistic and cultural influences on semantic fluency in monolingual Korean- and English-speaking individuals with Alzheimer's disease (AD) by contrasting culture-agnostic and culture-specific analytic frameworks. We focused on how culturally grounded schemas, such as the East Asian zodiac, shape clustering and switching patterns and on their associations with global cognition.

METHOD: We analyzed semantic fluency in 36 individuals with AD and 30 language-matched older adults using culture-agnostic and culture-specific frameworks. We examined total and first-response proportions of exemplars and compared clustering and switching patterns based on Troyer's taxonomy and a culture-specific scheme that included zodiac animals. All fluency measures were correlated with global cognition.

RESULTS: In Korean-speaking individuals with AD, animal fluency was shaped by culture-specific schemas, with zodiac animals frequently produced early and in clusters. This pattern-marked by greater clustering-was unique to the Korean group and was not detected using culture-agnostic analyses, which showed no group differences. Only the Korean group showed positive correlations between fluency and Mini-Mental State Examination scores.

CONCLUSIONS: The present findings suggest that culturally grounded schemas may influence both word generation and the organization of clustering and switching in semantic fluency. In Korean-speaking individuals with AD, zodiac animals formed structured clusters and switches that uniquely correlated with global cognition, highlighting the need for culturally informed norms in cross-linguistic neuropsychological assessment.

SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.33989638.},
}

@article {pmid42825842,
year = {2026},
author = {Martinez Holst, MA and Sierra Valiente, AM and Garcia-Becerra, CA},
title = {Incidence, severity, and associated risk factors for amyloid-related imaging abnormalities in anti-amyloid monoclonal antibody therapy for early Alzheimer's disease: a systematic review and meta-analysis.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {47},
number = {10},
pages = {},
pmid = {42825842},
issn = {1590-3478},
mesh = {Humans ; *Alzheimer Disease/drug therapy/diagnostic imaging/epidemiology/genetics ; Risk Factors ; *Antibodies, Monoclonal/adverse effects/therapeutic use ; Incidence ; *Amyloid beta-Peptides ; },
abstract = {BACKGROUND: Amyloid-related imaging abnormalities (ARIA) are the most concerning side effect of the treatment for early Alzheimer's disease (AD) with anti-amyloid monoclonal antibodies (mAbs).

OBJECTIVE: This study systematically evaluates the incidence, severity, and associated risk factors of ARIA in patients with early AD receiving anti-amyloid mAbs therapy.

METHODS: A comprehensive systematic review and meta-analysis were conducted following PRISMA guidelines. Assessed outcomes included ARIA incidence, symptomatic cases and severity, radiographic severity, and risk factors. Pooled incidences and odds ratios were estimated with a random effects model using the R software (version 4.5.2).

RESULTS: The systematic search yielded a total of 20 articles, representing 21 phase 3 randomized controlled trials that involved 12,610 AD patients. Pooled incidence was 5.4% for ARIA-E and 10.27% for ARIA-H. Most cases being asymptomatic and radiographically mild to moderate. Risk factor analysis revealed that ApoE 4 homozygotes carriers (OR = 5.12), ApoE 4 heterozygotes carriers (OR = 1.91), higher mAb dosage (OR = 2.0) and baseline microhemorrhages (OR = 1.43) had a major influence on ARIA-E occurrence, as for ARIA-H incidence was higher in ApoE 4 heterozygous (OR = 1.65) and homozygotes carriers (OR = 4.65). Moreover, ApoE 4 heterozygous and homozygotic carriers were associated with symptomatic (OR = 1.52;3.68) and severe radiographic (OR = 2.11;6.31) ARIA-E.

DISCUSSION: ARIA remains a significant safety concern in anti-amyloid mAb therapy, with incidence and severity influenced by genetic, neuroimaging, and treatment-related factors. Future research should focus on refining risk stratification and understanding long-term consequences of ARIA.},
}

Humans
*Alzheimer Disease/drug therapy/diagnostic imaging/epidemiology/genetics
Risk Factors
*Antibodies, Monoclonal/adverse effects/therapeutic use
Incidence
*Amyloid beta-Peptides

@article {pmid42825974,
year = {2026},
author = {Wu, J and Wang, Y and Zhao, M and Liu, J and Zhao, W},
title = {Bisphenol A Exposure Perturbs the Immune Microenvironment in Alzheimer's Disease: Insights from Network Toxicology and Single-Cell Transcriptomics.},
journal = {Journal of molecular neuroscience : MN},
volume = {76},
number = {4},
pages = {},
pmid = {42825974},
issn = {1559-1166},
mesh = {*Phenols/toxicity ; *Benzhydryl Compounds/toxicity ; *Alzheimer Disease/genetics/immunology/metabolism ; Bisphenol A Compounds ; Humans ; *Transcriptome ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; Single-Cell Analysis ; *Endocrine Disruptors/toxicity ; },
abstract = {Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder in which exposure to environmental endocrine-disrupting chemicals may contribute to disease susceptibility. Here, we integrated network toxicology, bulk transcriptomics, machine learning, immune deconvolution, single-nucleus transcriptomics, competing endogenous RNA (ceRNA) analysis, molecular docking, and 100-ns molecular dynamics (MD) simulations to investigate the potential molecular links between bisphenol A (BPA) exposure and AD. Cross-database integration identified 248 shared BPA-AD targets, from which 47 network-central genes and 19 differentially expressed genes were prioritized. Five genes-GSK3B, BCL2, EGFR, APP, and PPARD-were subsequently retained as a candidate gene signature. Although the resulting model showed strong discriminatory performance in the discovery cohort, substantially lower performance in validation cohorts indicated limited generalizability and potential overfitting. Functional analyses implicated neuroinflammatory signaling, mitochondrial apoptosis, amyloid-related processes, and lipid and metabolic dysregulation in the molecular association between BPA and AD. LM22-based CIBERSORT analysis revealed alterations in peripheral leukocyte-like immune signatures, which were interpreted cautiously because this reference matrix does not directly represent resident brain immune populations. Single-nucleus transcriptomic analysis of GSE163577 further localized key genes across biologically plausible cerebrovascular and neuroimmune cell populations. CeRNA analysis suggested potential post-transcriptional regulatory relationships associated with the identified hub genes, while molecular docking identified putative interactions between BPA and candidate target proteins. Subsequent 100-ns MD simulations further characterized the dynamic behavior and conformational stability of the selected BPA-protein complexes, providing complementary evidence for the docking-derived structural hypotheses. Collectively, these findings suggest that BPA-related molecular targets may converge on immune, vascular, metabolic, and neurodegenerative processes relevant to AD. However, the present findings remain primarily computational and hypothesis-generating, and experimental studies are required to establish causal and mechanistic relationships.},
}

*Phenols/toxicity
*Benzhydryl Compounds/toxicity
*Alzheimer Disease/genetics/immunology/metabolism
Bisphenol A Compounds
Humans
*Transcriptome
Molecular Docking Simulation
Molecular Dynamics Simulation
Single-Cell Analysis
*Endocrine Disruptors/toxicity

@article {pmid42826098,
year = {2026},
author = {Lin, W and Phanse, S and van der Spek, SJF and Lampl, N and Stephens, MC and Wang, Z and Nigro, JT and Ortiz, AR and Hekman, R and Cruz, ALF and Roberts, R and Jiang, L and Botas, J and Emili, A and Wolozin, B},
title = {Progressive remodeling of global protein interaction networks in a mouse model of tauopathy.},
journal = {Cell reports},
volume = {45},
number = {10},
pages = {118084},
doi = {10.1016/j.celrep.2026.118084},
pmid = {42826098},
issn = {2211-1247},
abstract = {Neurodegenerative disease is marked not just by loss of proteins or cells, but by dynamic rewiring of macromolecular interaction networks that precede and drive pathology. Here, we present a temporally resolved, systems-scale map of multi-protein complex remodeling in a tauopathy model, integrating co-fractionation mass spectrometry, quantitative phosphoproteomics, and machine learning to decode phosphorylation-dependent shifts in protein interactomes across disease progression. This interactomic atlas serves as a resource to investigate functional assemblies, including MAPT-Dpysl2 and Cyfip1-actin, as well as ptk2b-Kars/Dars and ptk2b-Msn-Farsb-complexes, that modulate early disease phenotypes in vivo. Notably, it captures the composition, dynamics, and regulatory state of protein complexes at scale. By revealing how phosphorylation tunes macromolecular complex architecture and function, this work highlights dynamic network instability that develops over the course of tauopathy, and establishes a generalizable framework for mechanistic dissection of functional complexes in neurodegeneration.},
}

@article {pmid42826267,
year = {2026},
author = {Amouzad-Lichahi, M and Petkov, I and Smerat, A and Alsarhan, HW and Letafatkar, N and Abbasnejad-Ardehroudkenari, M and Mohammadi, S and Jafari, M and Ghodous, S and Amini-Salehi, E},
title = {Prevalence of metabolic syndrome among patients with Alzheimer disease: A systematic review and meta-analysis.},
journal = {Medicine},
volume = {105},
number = {40},
pages = {e50670},
doi = {10.1097/MD.0000000000050670},
pmid = {42826267},
issn = {1536-5964},
mesh = {*Metabolic Syndrome/epidemiology ; Humans ; *Alzheimer Disease/epidemiology/complications ; Prevalence ; },
abstract = {BACKGROUND: The relationship between metabolic syndrome (MetS) and Alzheimer disease (AD) has gained increasing attention in recent years, reflecting the growing recognition of metabolic factors in neurodegenerative conditions. The present study aims to estimate the prevalence of MetS in patients with AD.

METHODS: A systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive literature search of PubMed, Scopus, and Web of Science was performed. Observational studies reporting the prevalence of MetS among patients with AD and/or providing comparative data with control groups were included. Pooled prevalence and odds ratios with 95% confidence intervals (CIs) were calculated using a random-effects model, and heterogeneity was assessed using the I2 statistic. Subgroup and meta-regression analyses were also performed.

RESULTS: Nine studies were included. The pooled prevalence of MetS among patients with AD was 46.7% (95% CI: 28.0%-65.8%; I2 = 97.11%). In subgroup analysis by continent, the prevalence was 26.1% (95% CI: 11.1%-44.4%) in Asia (I2 = 84.42%) and 52.8% (95% CI: 25.2%-79.5%) in Europe (I2 = 97.05%), while the estimate from North America was 72.2% (95% CI: 62.5%-81.0%) based on a single study. The comparative analysis showed an odds ratio of 1.64 (95% CI: 0.75-3.57), with no statistically significant association between AD and MetS. Meta-regression identified glucose as significantly associated with MetS prevalence (β = 0.022; P = .021).

CONCLUSION: MetS was frequently observed among patients with AD; however, the pooled prevalence estimate should be interpreted cautiously because of substantial between-study heterogeneity. The comparative analysis did not demonstrate a statistically significant association between AD and MetS. Further studies using standardized definitions and more homogeneous populations are needed to clarify this relationship and the sources of heterogeneity.},
}

*Metabolic Syndrome/epidemiology
Humans
*Alzheimer Disease/epidemiology/complications
Prevalence

@article {pmid42826310,
year = {2026},
author = {Lwere, K and Nakasujja, N and Muwonge, H and Sendagire, H and Gumikiriza-Onoria, JL and Buwembo, D and Buwembo, W and Kabwigu, S and Mukasa, JK and Kirya, F and Nazziwa, A and Othieno, E and Nassanga, R and Nakimbugwe, R and Munabi, IG and Sajatovic, M and Kaddumukasa, M},
title = {Systemic inflammation, gut microbiome composition, and cognitive performance among older Ugandans with Alzheimer's disease and related dementias: A cross-sectional study.},
journal = {Medicine},
volume = {105},
number = {40},
pages = {e50956},
doi = {10.1097/MD.0000000000050956},
pmid = {42826310},
issn = {1536-5964},
mesh = {Humans ; Cross-Sectional Studies ; Female ; Male ; *Gastrointestinal Microbiome/physiology ; *Alzheimer Disease/microbiology ; C-Reactive Protein/analysis/metabolism ; *Inflammation/blood ; Aged ; Uganda/epidemiology ; *Cognition/physiology ; *Cognitive Dysfunction ; Biomarkers/blood ; Aged, 80 and over ; East African People ; },
abstract = {Systemic inflammation is implicated in neurodegeneration; however, evidence linking circulating inflammatory biomarkers to cognitive decline remains inconsistent, particularly in low- and middle-income countries. High-sensitivity C-reactive protein (hs-CRP) is a standard systemic inflammatory marker; however, its relationship with cognitive performance and gut microbiome composition in sub-Saharan Africa remains underexplored. We investigated the association between hs-CRP and cognitive performance across older Ugandans diagnosed with Alzheimer disease (AD), mild cognitive impairment (MCI), and cognitively intact controls and examined whether gut microbial composition modified this relationship. We conducted a cross-sectional study of community-dwelling older adults in Wakiso District, Uganda. Cognitive performance was assessed using the Education-Adjusted Montreal Cognitive Assessment (MoCA). Systemic inflammation was quantified using plasma hs-CRP, and gut microbial profiles were generated via full-length 16S rRNA gene sequencing. Multivariable linear regression models were used to evaluate the associations between log-transformed hs-CRP concentrations and MoCA scores, adjusting for age, sex, and body mass index. Linear regression assumptions were formally tested. Exploratory analyses examined taxon-level differential abundance across diagnostic categories, hs-CRP-microbiome correlations, and hs-CRP × taxon interaction terms on MoCA scores, with multiple-testing adjustment using the false discovery rate. The analytic cohort comprised 85 participants (mean age 77.5 ± 9.2 years; 67 AD, 10 MCI, and 8 controls). Median hs-CRP was higher in AD (1.96 [0.25-3.75] mg/L) than in MCI (0.25 [0.25-2.73] mg/L) and controls (0.25 [0.25-0.84] mg/L). Higher hs-CRP showed a modest inverse trend with MoCA scores that was not statistically significant after adjustment for age, sex, and body mass index (standardized ,). Advancing age was independently associated with poorer cognitive performance (standardized ,). Several microbial genera exhibited nominal differences across diagnostic groups and hs-CRP levels; however, no individual taxon-level associations or hs-CRP × microbiome interaction terms survived false discovery rate correction (). Circulating hs-CRP was not independently associated with global cognitive performance in this cohort of older Ugandans. Genus-level microbiome analyses yielded exploratory, hypothesis-generating patterns that warrant validation in larger longitudinal cohorts investigating gut-brain axis interactions in African populations.},
}

Humans
Cross-Sectional Studies
Female
Male
*Gastrointestinal Microbiome/physiology
*Alzheimer Disease/microbiology
C-Reactive Protein/analysis/metabolism
*Inflammation/blood
Aged
Uganda/epidemiology
*Cognition/physiology
*Cognitive Dysfunction
Biomarkers/blood
Aged, 80 and over
East African People

@article {pmid42826326,
year = {2026},
author = {Zeng, Z and Shao, S and Deng, T and Zhou, S},
title = {Multiple chronic conditions and intrinsic capacity among middle-aged and older adults: Evidence from CHARLS.},
journal = {Medicine},
volume = {105},
number = {40},
pages = {e50947},
doi = {10.1097/MD.0000000000050947},
pmid = {42826326},
issn = {1536-5964},
support = {SXJYB2529//Sichuan Research Center for Sexology and Sex Education/ ; YF22-Q20//Sichuan Medical Law Research Center/ ; 2025RWY29//Humanities and Social Sciences Research Project of Sichuan Nursing Vocational College/ ; 2024SZS218//Deyang Science and Technology Program/ ; },
mesh = {Humans ; Aged ; Male ; China/epidemiology ; Female ; Middle Aged ; Longitudinal Studies ; *Multiple Chronic Conditions/epidemiology ; *Aging/physiology ; Cross-Sectional Studies ; Socioeconomic Factors ; Socioeconomic Disparities in Health ; },
abstract = {With the accelerating global aging process, maintaining intrinsic capacity (IC) among middle-aged and older adults has become a major public health priority. Multiple chronic conditions (MCC) are highly prevalent in later life and may contribute to declines in physical and mental functioning. However, evidence regarding the association between MCC and IC, as well as variations across disease types and socioeconomic contexts, remains limited. This study aimed to examine the association between MCC and IC among middle-aged and older adults and to explore heterogeneity across chronic disease categories, regional contexts, and individual characteristics. Data were obtained from the 2011, 2015, and 2018 waves of the China Health and Retirement Longitudinal Study. Using 28,613 pooled repeated cross-sectional person-wave observations, regression models incorporating survey-year and regional fixed effects were applied to examine the association between MCC and IC. Respondent-level cluster-robust standard errors were used to account for the nonindependence of repeated observations. Robustness analyses, instrumental variable estimation, and propensity score matching were conducted to assess the stability of the findings. Subgroup analyses were performed across macro-level (urban/rural residence and regional economic zones) and micro-level (sex, education, and household income) characteristics. MCC was significantly associated with lower IC (β = -0.076, P < .01). Disease-specific analyses showed that neurodegenerative diseases, including Parkinson disease and Alzheimer disease, demonstrated the strongest negative association with IC (β = -0.587, P < .01), followed by cardiovascular diseases (β = -0.135, P < .01). The negative association between MCC and IC was stronger among individuals living in rural areas and western regions, as well as among men, individuals with lower educational attainment, and those with lower household income. Robustness analyses, instrumental variable estimation, and propensity score matching yielded findings that were directionally consistent with the main analysis. MCC is significantly associated with reduced IC among middle-aged and older adults, with substantial heterogeneity across disease types and socioeconomic contexts. These findings highlight the importance of integrated chronic disease management, IC assessment, and targeted interventions for vulnerable populations, particularly those in socioeconomically disadvantaged regions, to promote healthy aging.},
}

Humans
Aged
Male
China/epidemiology
Female
Middle Aged
Longitudinal Studies
*Multiple Chronic Conditions/epidemiology
*Aging/physiology
Cross-Sectional Studies
Socioeconomic Factors
Socioeconomic Disparities in Health

@article {pmid42826335,
year = {2026},
author = {Xiong, Y and Wei, K and Fang, J},
title = {The association between Naples prognostic score and cognitive function in older adults: A cross-sectional study of NHANES 2011 to 2014.},
journal = {Medicine},
volume = {105},
number = {40},
pages = {e51026},
doi = {10.1097/MD.0000000000051026},
pmid = {42826335},
issn = {1536-5964},
mesh = {Humans ; Cross-Sectional Studies ; Female ; Male ; Aged ; *Cognition/physiology ; Nutrition Surveys ; Prognosis ; Neuropsychological Tests ; Middle Aged ; Alzheimer Disease/diagnosis ; United States/epidemiology ; Logistic Models ; },
abstract = {The purpose of this study was to examine the association between the Naples prognostic score (NPS) and cognitive function in older adults. This cross-sectional study analyzed data from 2759 participants aged 60 years and older, with a mean age of 69.2 ± 6.6 years, from the National Health and Nutrition Examination Survey 2011 to 2014 data. Participants were categorized into 2 groups based on NPS: Group 1 (NPS = 0-2) and Group 2 (NPS = 3-4). Cognitive function was assessed using the Consortium to Establish a Registry for Alzheimer's Disease Word Learning subtest, Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST). A global composite z-score was also calculated. Multivariable linear and logistic regression models were used to examine the associations between NPS and cognitive outcomes, with adjustments for sociodemographic and health-related confounders. In the fully adjusted models, a higher NPS was associated with lower AFT, DSST, and composite z-scores, whereas no significant association was observed with the Consortium to Establish a Registry for Alzheimer's Disease Word Learning subtest score. Compared with the low-NPS group, the high-NPS group had significantly lower AFT scores (β = -1.39, 95% confidence interval [CI]: -1.89 to -0.88), DSST scores (β = -1.82, 95% CI: -3.11 to -0.53), and composite z-scores (β = -0.43, 95% CI: -0.62 to -0.24), all with P < .05. Logistic regression further showed that the high-NPS group had higher odds of cognitive impairment according to the AFT (odds ratio = 1.41, 95% CI: 1.04-1.92) and DSST (odds ratio = 1.47, 95% CI: 1.00-2.14), both with P < .05. No statistically significant interactions were detected in the subgroup analyses (all P for interaction > .05). This study revealed the possible association between a high NPS and poorer cognitive performance, especially in terms of verbal fluency and processing speed. These findings suggest that the NPS may provide supplementary information for identifying individuals with poorer cognitive performance. However, the cross-sectional design precludes temporal or causal inference.},
}

Humans
Cross-Sectional Studies
Female
Male
Aged
*Cognition/physiology
Nutrition Surveys
Prognosis
Neuropsychological Tests
Middle Aged
Alzheimer Disease/diagnosis
United States/epidemiology
Logistic Models

@article {pmid42826355,
year = {2026},
author = {Bevilacqua, R and Maranesi, E and Felici, E and Marziali, RA and Margaritini, A and Sgolastra, A and Paciaroni, L and Raccichini, A and Pelliccioni, G and Grassi, L and Recchiuto, CT and Lattanzio, F and Sgorbissa, A and Amabili, G},
title = {Technology-Assisted Cognitive Support for Older Adults With Mild Cognitive Impairment: Study Protocol for the DHEAL-COM COGNITIVE Quasi-Experimental Pilot Study.},
journal = {JMIR research protocols},
volume = {15},
number = {},
pages = {e80233},
doi = {10.2196/80233},
pmid = {42826355},
issn = {1929-0748},
mesh = {Humans ; Pilot Projects ; *Cognitive Dysfunction/therapy/psychology ; Aged ; Cognitive Training/methods ; Feasibility Studies ; Single-Blind Method ; Female ; Male ; Cognitive Enhancement ; Aged, 80 and over ; },
abstract = {BACKGROUND: Mild cognitive impairment (MCI) represents a transitional phase between normal aging and dementia. While no pharmacological treatments have proven effective, nonpharmacological interventions, such as cognitive stimulation and psychosocial support, have shown promise. Integrating digital tools and socially assistive robotics may improve engagement, personalization, and access to care, contributing to the preservation of cognitive function and overall well-being in older adults.

OBJECTIVE: The DHEAL-COM COGNITIVE pilot study aims to evaluate the feasibility, acceptability, and preliminary efficacy of a sociotechnological intervention that combines digital cognitive stimulation, social robot interaction, and group training in digital and health literacy to counteract cognitive decline.

METHODS: This is a single-blind, quasi-experimental feasibility trial involving 60 older adults with MCI, recruited from the Neurology and Alzheimer Units of IRCCS INRCA (INRCA - IRCCS Istituto Nazionale di Ricovero e Cura per Anziani). Participants were allocated into 2 groups: the experimental group received home-based cognitive training via the Brainer app, a month-long interaction with the NAO social robot, and weekly group sessions on eHealth literacy and cognitive stimulation; the control group received a well-being booklet with optional activities. Assessments were conducted at baseline, postintervention after 12 weeks, and follow-up after 3 months, using validated instruments, such as the Montreal Cognitive Assessment, the EQ-5D-5L, the Italian version of the eHealth Literacy Scale, the System Usability Scale, the unified theory of acceptance and use of technology, and the Psychological Well-Being Scale. Descriptive statistics will be used to summarize feasibility, usability, and acceptability outcomes, while preliminary differences over time will be explored using appropriate inferential analyses, acknowledging that the study is not powered to detect effectiveness.

RESULTS: Patient recruitment began in March 2025 and continued through September 2025. As of April 2026, 36 patients have been recruited, with 18 participants per group. The trial started in May 2025 and ran throughout the year. Results will focus on changes in cognitive performance, psychological well-being, quality of life, eHealth literacy, and user acceptability and usability of the technologies. Findings will be analyzed quantitatively and qualitatively and are expected to be published by the end of 2026.

CONCLUSIONS: The DHEAL-COM COGNITIVE study proposes an innovative, integrated intervention for older adults with MCI, using digital platforms and social robotics to support cognitive health and autonomy. This pilot study represents a promising step toward a more integrated and technology-supported model of care for older adults with MCI.},
}

Humans
Pilot Projects
*Cognitive Dysfunction/therapy/psychology
Aged
Cognitive Training/methods
Feasibility Studies
Single-Blind Method
Female
Male
Cognitive Enhancement
Aged, 80 and over

@article {pmid42826515,
year = {2026},
author = {Das, B and Baidya, AT and Chouhan, D and Gupta, HK and Thakur, B and Darreh-Shori, T and Chen, G and Tiwari, V and Kumar, R},
title = {Rational design, synthesis, and biological evaluation of indole-piperazine based α-ketoamide derivatives as dual Aβ and tau aggregation modulators for Alzheimer's disease.},
journal = {European journal of medicinal chemistry},
volume = {320},
number = {},
pages = {119353},
doi = {10.1016/j.ejmech.2026.119353},
pmid = {42826515},
issn = {1768-3254},
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by pathological aggregation of amyloid-β (Aβ) and tau proteins, representing two major hallmarks of disease progression. Targeting both aggregation pathways simultaneously offers a promising therapeutic strategy. Building upon our previous identification of the α-ketoamide derivative BD23 as a dual aggregation modulator, we report the rational design, synthesis, and biological evaluation of a new series of indole-piperazine based α-ketoamide moiety. A focused library of twenty-four compounds was synthesized and characterized using nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry (HRMS). These compounds were evaluated for modulation of Aβ42 aggregation using the thioflavin T fluorescence assay. Several derivatives significantly altered fibrillization kinetics, with MD03, MD07, MD08, and MD10 emerging as the most active candidates. Among them, MD08 exhibited optimal aqueous solubility (0.037 ± 0.0035 mg/mL) along with moderate blood-brain barrier permeability (Pe = 3.42 ± 0.33 × 10[-6] cm/s). Further evaluation demonstrated that MD08 inhibited heparin-induced tau aggregation in vitro, without cytotoxicity in human neuroblastoma (SH-SY5Y) cells. In vivo studies in an Aβ-induced cognitive decline mouse model revealed significant cognitive improvement in a dose-dependent manner (2, 5, and 10 mg/kg), with the highest dose showing efficacy comparable to the standard drug donepezil. Complementary in silico studies, including molecular docking and molecular dynamics simulations, supported stable interactions with Aβ and tau. Collectively, these findings identify MD08 as a promising dual aggregation modulator for AD, warranting further preclinical investigation.},
}

@article {pmid42826575,
year = {2026},
author = {Tripathi, A and Yadav, AK and Kumar, N},
title = {AI-driven transcriptomics for neurodegenerative disease research: A systematic review.},
journal = {Computational biology and chemistry},
volume = {126},
number = {Pt 1},
pages = {109448},
doi = {10.1016/j.compbiolchem.2026.109448},
pmid = {42826575},
issn = {1476-928X},
abstract = {BACKGROUND: Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), and Amyotrophic Lateral Sclerosis (ALS), present a growing global health challenge, with traditional diagnostic and therapeutic approaches facing significant limitations in early detection and mechanistic resolution.

OBJECTIVES: Innovations in transcriptomic technologies-spanning bulk RNA sequencing, single-cell RNA-seq (scRNA-seq), and spatially resolved transcriptomics-provide unprecedented insights into cellular heterogeneity and microenvironmental dysregulation. This systematic review synthesizes recent applications of artificial intelligence (AI), machine learning (ML), and deep learning (DL) across transcriptomic tiers to benchmark computational models for biomarker identification, disease diagnosis, patient subtyping, and drug repurposing.

METHODS & ELIGIBILITY: Following PRISMA 2020 guidelines for qualitative systematic reviews, literature published between 2016 and 2025 was systematically searched across PubMed/MEDLINE, IEEE Xplore, Google Scholar, and bioRxiv/medRxiv. Of 1058 records identified, 19 core empirical studies met all eligibility criteria and were synthesized in depth alongside contextual reference benchmarks.

SYNTHESIS & KEY FINDINGS: Traditional ML algorithms (SVM, RF, Elastic Net) demonstrate high diagnostic accuracy (AUC 0.72-0.98) in blood-based biomarker selection, while deep architectures (autoencoders, LSTMs, and Graph Neural Networks) excel at modeling continuous disease trajectories and resolving spatial transcriptomic niches (e.g., STAGATE, SpaGCN, cell2location). Emerging spatial deep learning models successfully localize disease-associated microglia (DAM) around amyloid plaques and trace axonal degeneration pathways.

LIMITATIONS & CONCLUSIONS: Key translational hurdles include data scarcity in rare NDD subtypes, lack of cross-platform spatial benchmarks, and the black-box nature of deep neural networks. Integrating explainable AI (XAI) and prospective multi-modal cohorts is essential for translating computational transcriptomics into clinical diagnostics and targeted therapeutics.},
}

@article {pmid42826598,
year = {2026},
author = {Rava, A and Di Trapano, M and Tse, C and Ji, L and Bid, HK and Trezza, V},
title = {Acidic cannabinoids in brain disorders: Neurobiological mechanisms, preclinical evidence, and translational challenges.},
journal = {Neuroscience and biobehavioral reviews},
volume = {191},
number = {},
pages = {107005},
doi = {10.1016/j.neubiorev.2026.107005},
pmid = {42826598},
issn = {1873-7528},
abstract = {Acidic cannabinoids, including tetrahydrocannabinolic acid (THCA), cannabidiolic acid (CBDA), cannabigerolic acid (CBGA), and related biosynthetic precursors, represent the predominant phytocannabinoid forms naturally produced by Cannabis sativa. Long considered pharmacologically inactive intermediates, these compounds are now increasingly recognized as bioactive molecules with potential therapeutic relevance for brain disorders. Compared with their decarboxylated counterparts, acidic cannabinoids exhibit distinct physicochemical, pharmacokinetic, and pharmacodynamic properties that may confer reduced psychotropic liability together with unique neurobiological effects. Emerging preclinical evidence indicates that acidic cannabinoids modulate multiple processes implicated in neurological and psychiatric disorders, including serotonergic and endocannabinoid signaling, neuroinflammation, oxidative stress, mitochondrial dysfunction, calcium dyshomeostasis, and synaptic transmission. In this review, we critically examine current knowledge regarding acidic cannabinoids in the context of brain disorders. We first summarize their biosynthesis, chemical stability, pharmacokinetic characteristics, and pharmacological differences from neutral cannabinoids. We then examine preclinical evidence supporting their potential therapeutic effects in epilepsy, anxiety, depression, psychosis-related conditions, and neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. We also discuss how artificial intelligence and computational approaches may support target identification, formulation optimization, pharmacokinetic modeling, and the development of personalized cannabinoid-based interventions. Finally, we highlight key methodological and translational challenges limiting the field and outline priorities for future research. Overall, acidic cannabinoids emerge as promising but still underexplored multitarget compounds with potential relevance for the treatment of brain disorders.},
}

@article {pmid42826610,
year = {2026},
author = {Rodriguez, S and Wetmore, JB and Diaz Caro, D and Cabán, M and Uhlmann, WR and Roberts, JS and Siegel, K and Ottman, R},
title = {Numeracy and recall of Alzheimer's disease risk information: Effects of risk format in a Latino community.},
journal = {Patient education and counseling},
volume = {154},
number = {},
pages = {110330},
doi = {10.1016/j.pec.2026.110330},
pmid = {42826610},
issn = {1873-5134},
abstract = {PURPOSE: Accurate recall of risk information is essential for informed decision-making, yet the influence of numeracy on risk recall among Latinos is unknown. We examined the relations of numeracy to recall of Alzheimer's disease (AD) risk and APOE genotypes among Latino participants in the IDEAL Study.

METHODS: Latinos aged 40-64 (N = 310) randomized to receive AD risk estimates to age 85 with or without APOE genotype information completed five numeracy items before risk disclosure. Risk estimates were delivered by genetic counselors in two formats: percentage and number out-of-20. Six weeks after disclosure, participants reported recall of risks in both formats, risk relative to other Latinos in their community, APOE-ε4 carrier status, and APOE genotype. Logistic regression was used to assess associations of numeracy with recall accuracy, adjusting for sociodemographic factors.

RESULTS: Numeracy was increased among men, participants of Mexican descent, and those who had higher education, higher income, or greater identification with non-Latinos. Among all participants, 40% correctly recalled their exact risk percentage and 37% correctly recalled their exact risk estimate out-of-20. Among participants told their APOE genotype, 75% correctly recalled their APOE-ε4 carrier status, but only 24% their specific genotype. Higher numeracy was associated with better recall of risk estimates presented out-of-20, but not with recall of genotype, percentage-based risk estimates, or risk relative to others.

CONCLUSIONS: Numeracy was associated with recall of some, but not all, forms of AD risk information. Percentage-based risk estimates were recalled somewhat better overall, and recall of risk presented out-of-20 was dependent on numeracy.

PRACTICE IMPLICATIONS: Selection of risk formats that minimize cognitive burden may improve retention of risk information, particularly among persons with lower numeracy. Use of simplified numeric formats and supportive communication strategies may enhance the effectiveness of AD risk disclosure in diverse populations.},
}

@article {pmid42826647,
year = {2026},
author = {Esmaeili, H and Das, S and Rytel, K and Sidransky, E and Chen, Y},
title = {CRISPR screening in neurodegeneration and lysosomal biology: Uncovering disease mechanisms and genetic modifiers.},
journal = {Molecular genetics and metabolism},
volume = {149},
number = {3},
pages = {110265},
doi = {10.1016/j.ymgme.2026.110265},
pmid = {42826647},
issn = {1096-7206},
abstract = {Growing genetic and mechanistic evidence has highlighted substantial convergence between neurodegenerative disorders and lysosomal biology. Variants in lysosomal protein-encoding genes associated with lysosomal storage disorders (LSDs) have been implicated in common neurodegenerative diseases, suggesting that perturbations of lysosomal function represent a shared pathogenic mechanism. However, the low penetrance of neurodegenerative diseases in individuals carrying variants in these lysosomal genes suggests that additional genetic modifiers are involved as well. Advances in functional genomics, particularly clustered regularly interspaced short palindromic repeat (CRISPR)-based high-throughput screens, have opened new avenues to identify such modifiers and elucidate disease-associated pathways. These unbiased approaches have accelerated the discovery of molecular mechanisms underlying neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Although to date few studies have applied CRISPR-based functional screens directly to LSDs, findings from neurodegenerative disease models provide a valuable framework for investigating lysosomal pathways and identifying genetic factors that influence phenotypic variability. In this review, we summarize recent advances in in vitro CRISPR-based screening approaches in neurodegenerative disorders and discuss their implications for understanding lysosomal biology and LSD-related mechanisms.},
}

@article {pmid42826663,
year = {2026},
author = {Paparella, M and Leuci, R and Cerini, M and Simic, S and Chaves, S and Carrieri, A and Loiodice, F and Tortorella, P and Laghezza, A and Wackerlig-Damle, J and Santos, MA and Piemontese, L},
title = {Structural optimization of donepezil-like hybrids toward an improved multi-target and ADME-related profile.},
journal = {Bioorganic chemistry},
volume = {183},
number = {},
pages = {110599},
doi = {10.1016/j.bioorg.2026.110599},
pmid = {42826663},
issn = {1090-2120},
abstract = {Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder involving mainly cholinergic dysfunction, protein misfolding, and metal dyshomeostasis. Considering the complexity of the pathology, multi-target approaches represent a valuable alternative to current approved mono-target treatments. In this study, starting from two previously identified lead compounds, fifteen new derivatives were designed. Various functional groups were introduced to evaluate their impact on cholinesterases (ChEs) and fatty-acid amide hydrolase (FAAH) and in some cases potent selective human acetylcholinesterase inhibition was observed (IC50 up to 9 ± 1 nM for compound 1 and 3). Among the series, the amine-based derivatives (9 and 11) were further evaluated for Fe[3+], Cu[2+], and Zn[2+] chelation ability, under a metal targeted strategy, showing high selectivity (pFe[3+] = 16.1, pCu[2+] = 11.0 and pZn[2+] = 6.03 for compound 11) and a metal-binding pattern suitable for anti-AD activity. Additionally, these molecules exhibited noteworthy antioxidant properties (IC50 = 17-45 μM for compounds 9-11), thus potentially beneficial in overcoming ROS overproduction typical of the disease. Finally, the whole series was subjected to an extensive in vitro ADME-related profiling, showing promising experimental ADME-related properties.},
}

@article {pmid42826681,
year = {2026},
author = {Xu, F and Li, H and Yan, Y and Chen, L and Sheng, Z and Dou, B and Yan, C and Zhu, X and Xu, Y},
title = {Cyclic nucleotide signaling through phosphodiesterase 1 inhibition and its interaction with the competing endogenous RNA network regulates cognition.},
journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie},
volume = {204},
number = {},
pages = {119963},
doi = {10.1016/j.biopha.2026.119963},
pmid = {42826681},
issn = {1950-6007},
abstract = {BACKGROUND: Phosphodiesterase 1 (PDE1) has been demonstrated to be a potential drug target for a variety of diseases, ranging from peripheral system disease (PSD) to central nervous system disorders (CNSD). However, how cyclic nucleotide signaling, regulated by PDE1, particularly its isoform PDE1A, regulates the pathology of neurodegenerative disorders, including Alzheimer's disease (AD), remains unclarified.

METHOD: The Gene Expression Omnibus (GEO) database, a public gene expression repository, was used to analyze the role of PDE1 dysfunction in AD pathology. The mRNA and long non-coding RNA (lncRNA) were analyzed by comparing their differences in the GENCODE data resource V22. The relationship between PDE1, particularly PDE1A, and competing endogenous RNA (ceRNA) was validated by a dual-luciferase assay and reverse transcription-quantitative PCR (RT-qPCR), suggesting a potential ceRNA relationship among XIST, miR-338-3p, and PDE1A. Further cell-based assay and behavioral tests were conducted to determine the neuroprotective and memory-enhancing effects of PDE1 inhibition in cell and mouse models of AD.

RESULTS: A total of 11,781 differentially expressed genes (DEGs) were identified as AD- related genes. Approximately 1131 genes were identified as mitochondrial dysfunction-related by Venn plot analysis and were closely associated with AD pathology. PDE1, especially PDE1A, interacts with the lncRNA-microRNA network to promote cellular infiltration. These bioinformatic analyses were further supported by cell-based assays and behavioral studies, which demonstrated that treatment with the PDE1 inhibitor vinpocetine and PDE1A knockout ameliorated mitochondrial morphological abnormalities, restored immune function, and enhanced memory in a mouse model of AD.

CONCLUSION: These findings demonstrate that PDE1, particularly PDE1A activity, plays critical roles in AD progression by modulating mitochondrial morphology, immunity, and neuronal function, ultimately contributing to cognitive deficits.},
}

@article {pmid42826718,
year = {2026},
author = {Cha, Y and Kim, KS},
title = {From patient cells to patient therapy: Twenty years of iPSC-based translation in neurodegenerative disease.},
journal = {Cell reports. Medicine},
volume = {},
number = {},
pages = {103104},
doi = {10.1016/j.xcrm.2026.103104},
pmid = {42826718},
issn = {2666-3791},
abstract = {Twenty years after the discovery of induced pluripotent stem cells, the field has progressed from patient-specific disease modeling toward cell-based therapies for neurodegenerative disorders. Parkinson's disease has emerged as the leading model for neuronal replacement, whereas Huntington's disease, Alzheimer's disease, and amyotrophic lateral sclerosis require distinct combinations of circuit reconstruction, cellular support, immune modulation, and engineered therapeutic delivery. We discuss key determinants of clinical translation, including cell source, product identity, graft composition, graft-host interactions, manufacturing reproducibility, genomic integrity, and clinical evaluation. We propose that the interval between cell transplantation and long-term engraftment constitutes a biological "black box" in which graft fate and therapeutic outcome are determined. As regenerative medicine enters its third decade, future progress will depend not only on generating therapeutic cells but also on elucidating and engineering the biological processes that determine their fate after transplantation, marking a conceptual transition from stem cell biology toward transplantation biology.},
}

@article {pmid42826722,
year = {2026},
author = {Murata, K and Mizushina, Y and Izawa, D and Matsui, Y and Wakabayashi, T and Hashimoto, T and Iwatsubo, T and Matsushima, Y},
title = {Ruscus aculeatus Extract Inhibits Amyloid Beta Production and Upregulates the Active form of ADAM10 in Human Neural Progenitor Cells.},
journal = {Planta medica},
volume = {},
number = {},
pages = {},
doi = {10.1055/a-2943-8874},
pmid = {42826722},
issn = {1439-0221},
abstract = {Alzheimer's disease is characterized by the accumulation of cerebral amyloid beta (Aβ) peptides, making the inhibition of Aβ production a key therapeutic strategy. We screened a plant extract library for Aβ42 inhibitors using human neural progenitor cells and identified a Ruscus aculeatus extract as a potential candidate. Although rhizome extracts of R. aculeatus exhibit vasotonic, and anti-inflammatory properties, their effects on amyloid-β precursor protein (APP) processing have not been investigated. We aimed to elucidate how R. aculeatus extract influences Aβ production and its underlying mechanisms. R. aculeatus extract significantly reduced Aβ40 and Aβ42 production and the pathogenic Aβ42/Aβ40 ratio in both human neural progenitor (ReNcell VM) and mouse neuroblastoma (Neuro2a) cells in concentration-dependent manner. The extract enhanced non-amyloidogenic APP pathway processing, evidenced by increased levels of ADAM10 active form, soluble APPα and C-terminal fragment α levels. Despite increasing BACE1 protein levels, the extract reduced soluble APPβ production, suggesting inhibition of BACE1-mediated APP cleavage. RNA-seq analysis revealed Notch signaling pathway downregulation, implying γ-secretase activity modulation. In conclusion, the R. aculeatus extract suppresses Aβ production by modulating multiple APP processing pathways, primarily through enhancing non-amyloidogenic pathway via ADAM10 activation. By reducing amyloidogenic peptides levels, R. aculeatus extract may contribute to decreased amyloid plaques formation. These findings identify R. aculeatus extract as a modulator of APP metabolism.},
}

@article {pmid42826818,
year = {2026},
author = {Chaudhari, A and Goyal, S},
title = {Microglial GPR56 in synaptic pruning: mechanisms, comparative receptor biology, and context-dependent roles in brain disorders.},
journal = {Biochimica et biophysica acta. Molecular cell research},
volume = {},
number = {},
pages = {120231},
doi = {10.1016/j.bbamcr.2026.120231},
pmid = {42826818},
issn = {1879-2596},
abstract = {Microglia regulate synaptic remodelling, eliminating weakened and dysfunctional synapses to maintain circuit development and homeostasis. Adhesion G protein-coupled receptor G1 (ADGRG1/GPR56) has emerged as a distinctive regulator integrating phosphatidylserine recognition, mechano-transduction, and G-protein signalling. This review synthesises the molecular, cellular and disease-level evidence, distinguishing throughout between direct experimental findings, associations, and proposed mechanisms. We discuss its structural organisation, the microglia-enriched splice variant 4 (S4), and how phosphatidylserine-exposing synapses are recognised and engulfed. The Gα12/13-RhoA cascade placed downstream of microglial GPR56 was defined in neural progenitor cells and has not been perturbed in microglia; it is presented as proposed rather than established. Comparison with CR3, CX3CR1, TREM2, MERTK, MEGF10 and BAI1, identifies microglia-enriched alternative splicing, direct coupling of phosphatidylserine recognition to G-protein signalling, and mechanosensitivity as distinguishing features. We then evaluate evidence linking GPR56 to traumatic brain injury, major depressive disorder, maternal immune activation models, and Alzheimer's disease. In every context the causal evidence is loss-of-function: removing the receptor worsens the phenotype, including in Alzheimer's disease, where microglial ADGRG1 is increased yet deletion aggravates amyloid pathology and cognitive decline. The evidence supports a protective receptor that, when lost, produces different outputs in different settings, not one that switches between protective and pathological roles. The four disease outcomes are different from each other and from developmental pruning. The idea that they all involve a single S4-dependent mechanism remains a hypothesis, not a confirmed fact. We conclude by discussing therapeutic and biomarker opportunities and translational challenges.},
}

@article {pmid42827109,
year = {2026},
author = {Song, J and Lee, SJ and Mook-Jung, I},
title = {Golgi dysfunction in Alzheimer disease: from human multiomic signatures to therapeutic targets.},
journal = {Experimental & molecular medicine},
volume = {},
number = {},
pages = {},
pmid = {42827109},
issn = {2092-6413},
abstract = {Deciphering the intricate pathogenesis of Alzheimer disease (AD) has been a highly demanding task for researchers for decades. Evidence from from human multiomic studies provides critical insights into complex disease mechanisms and drives novel findings. However, the data are often selectively comprehended, leaving a few notable factors underappreciated in the research field. We focus on the Golgi apparatus, one of the most undervalued organelles in AD research, to demonstrate its multidimensional contribution to the pathogenesis. Given the importance of Golgi in modulating intracellular protein and lipid homeostasis, implication of Golgi in AD pathogenesis deserves thorough investigation. In this review, we describe changes in Golgi morphology and function in AD, and summarize specific Golgi-related factors discovered by genomic, transcriptomic, proteomic, and lipidomic data using human samples. Based on the findings, we demonstrate mechanistic link of Golgi-related factors to AD pathogenesis and highlight potential therapeutic strategies to modify Golgi-mediated pathogenesis. Overall, Golgi dysfunction may serve as a notable mechanistic hub of AD pathogenesis, making it a promising target for development of novel therapeutic strategies.},
}

@article {pmid42827268,
year = {2026},
author = {Abdulhameed, N and Babin, A and Hansen, K and Weaver, R and Banks, WA and Talbot, K and Rhea, EM},
title = {Correction: Comparing regional brain uptake of incretin receptor agonists after intranasal delivery in CD-1 mice and the APP/PS1 mouse model of Alzheimer's disease.},
journal = {Alzheimer's research & therapy},
volume = {18},
number = {1},
pages = {},
pmid = {42827268},
issn = {1758-9193},
}

@article {pmid42819539,
year = {2026},
author = {Takahashi, R and Kashibayashi, T and Fujita, J and Yoshida, K and Hashiramoto, A and Kowa, H and Mizuta, E},
title = {Baseline CSF tau and short-term clinical change during lecanemab therapy: A prospective real-world cohort study in Japan.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {4},
pages = {e70487},
pmid = {42819539},
issn = {2352-8729},
abstract = {INTRODUCTION: Real-world prognostic evidence for cerebrospinal fluid (CSF) biomarkers during lecanemab therapy remains limited. We examined whether baseline CSF phosphorylated tau 181 (pTau181), total tau, and amyloid beta (Aβ) 42/Aβ40 were associated with 6-month clinical change.

METHODS: This prospective single-center cohort included 50 patients with early Alzheimer's disease spectrum treated with lecanemab. CSF biomarkers were measured using the Lumipulse G system. The primary outcome was 6-month change in Clinical Dementia Rating Sum of Boxes (CDR-SB). Models were adjusted for age, sex, and baseline Mini-Mental State Examination; sensitivity analyses included APOE ε4 status.

RESULTS: CDR-SB worsening occurred in 19 participants (38.0%). Higher pTau181 (β per SD = 0.408; 95% CI: 0.106 to 0.709; p = 0.0091) and total tau (β = 0.341; 95% CI: 0.032 to 0.651; p = 0.0314) were associated with worsening. Aβ42/Aβ40 was not.

DISCUSSION: Baseline CSF pTau181 and total tau were associated with 6-month clinical trajectories, supporting cautious cohort-level risk stratification.},
}

@article {pmid42819642,
year = {2026},
author = {Yang, X and Hu, P and Han, W and Dong, L and Zhang, H and Wang, J and Chen, H},
title = {Research advances in red ginseng polysaccharides: preparation, structural characteristics and immunomodulatory effect.},
journal = {Frontiers in pharmacology},
volume = {17},
number = {},
pages = {1929729},
pmid = {42819642},
issn = {1663-9812},
abstract = {Red ginseng is a processed product of ginseng through steaming. Its polysaccharides differ in structure and biological activity from those of ginseng. Red ginseng polysaccharides are mostly acidic polysaccharides and have various biological activities. It is worth noting that its immunomodulatory effect has become an important area of research. Pharmacological studies have shown that polysaccharides from red ginseng can enhance immunity through various pathways, such as affecting immune cell activity, regulating cytokine levels, promoting immune organ development, and regulating gut microbiota. In addition, red ginseng polysaccharide has other pharmacological effects, such as anti-diabetic effect, anti-Alzheimer's disease effect, health benefits for the skin, anticancer effect, and cardioprotective effect. This article reviews the extraction, purification, structural characterization, and biological activity of polysaccharides from red ginseng to elucidate their pharmacological effects and potential molecular mechanisms. In addition, this review also discusses the current research status of red ginseng polysaccharides, pointed out the existing gaps, and proposed innovative perspectives for better development of red ginseng polysaccharides.},
}

@article {pmid42819698,
year = {2026},
author = {Khawar, M and Bakthavatchalam, P},
title = {The Promise of Blood-Based Biomarkers in Early Detection and Care of Alzheimer's Disease.},
journal = {Nepal journal of epidemiology},
volume = {16},
number = {2},
pages = {1436-1437},
pmid = {42819698},
issn = {2091-0800},
}

@article {pmid42820100,
year = {2026},
author = {Le, LNN and Wheeler, GJ and Blockley, NP and Fletcher, E and Jung, Y and Farias, SET and Gavett, B and DeCarli, C and Fan, AP},
title = {Oxygen extraction fraction mapping between normal cognition and mild cognitive impairment in older adults using quantitative BOLD.},
journal = {Imaging neuroscience (Cambridge, Mass.)},
volume = {4},
number = {},
pages = {},
pmid = {42820100},
issn = {2837-6056},
mesh = {Humans ; *Cognitive Dysfunction/diagnostic imaging/metabolism/physiopathology ; *Magnetic Resonance Imaging/methods ; *Oxygen/metabolism/blood ; Aged ; Female ; *Cognition/physiology ; Male ; *Brain/diagnostic imaging/metabolism ; *Aging/physiology/metabolism ; Brain Mapping/methods ; Bayes Theorem ; Aged, 80 and over ; },
abstract = {Oxygen extraction fraction (OEF) represents the proportion of oxygen utilized by the brain from the blood and is a sensitive biomarker in understanding the vascular interplay between oxygen supply and demand. Alterations in OEF are increasingly recognized in normal aging and the pathophysiology of many neurological disorders, including Alzheimer's disease and cognitive impairment. Here, we aimed to assess regional OEF MRI in older adults and investigate its relationship with mild cognitive impairment (MCI) and normal aging using a Variational Bayesian quantitative BOLD (qBOLD) framework. The qBOLD model leverages a biophysical relationship between OEF, deoxygenated blood volume (DBV), and the reversible transverse relaxation rate (R2 [']) to extract parameter values from asymmetric spin echo (ASE) MRI scans. The reliability of these parameter estimates was enhanced by Variational Bayesian inference, which incorporates prior distributions that we optimized in numerical simulation. We then applied this model to a cohort of older adults (N = 70) from the Alzheimer's Disease Research Center (ADRC) at the University of California, Davis, including 58 cognitively normal (CN) and 12 amnestic mild cognitive impaired (MCI) participants. Our findings revealed a trend of elevated OEF across many cortical brain regions in the MCI group. Additionally, we identified regional positive associations between OEF and age in the MCI group, significantly in the left inferior parietal region (β = 0.88 ± 0.23 , T = 3.75 , P = 0.0004). Furthermore, the relationship between OEF and episodic memory in the right parahippocampal region differed significantly between two diagnostic groups (negative for CN and positive for MCI) (β = 0.09 ± 0.02 , T = 3.77 , P = 0.0004). This work adopts a novel qBOLD MRI framework for studying OEF changes in cognitive impairment as a potential biomarker for monitoring pathophysiology in aging and dementia.},
}

Humans
*Cognitive Dysfunction/diagnostic imaging/metabolism/physiopathology
*Magnetic Resonance Imaging/methods
*Oxygen/metabolism/blood
Aged
Female
*Cognition/physiology
Male
*Brain/diagnostic imaging/metabolism
*Aging/physiology/metabolism
Brain Mapping/methods
Bayes Theorem
Aged, 80 and over

@article {pmid42820135,
year = {2026},
author = {Zaraska, M},
title = {Our Tears Can Help Diagnose Cancer, Parkinson's, and Alzheimer's.},
journal = {ACS central science},
volume = {12},
number = {9},
pages = {1273-1276},
doi = {10.1021/acscentsci.6c01440},
pmid = {42820135},
issn = {2374-7943},
abstract = {Eye swabs, bioassays, and even smart contact lenses can "pick up" biomarkers for various conditions.},
}

@article {pmid42820145,
year = {2026},
author = {Weng, Q and Goldstein, BA and Engelhard, MM},
title = {Censoring-Aware Reinforcement Learning to Optimize Early Risk Alerts from Longitudinal Clinical Data.},
journal = {Proceedings of machine learning research},
volume = {340},
number = {},
pages = {2151-2174},
pmid = {42820145},
issn = {2640-3498},
abstract = {Early recognition of chronic conditions is critical to ensure patients receive timely interventions and support. Passive surveillance of routine electronic health records (EHRs) provides information about longitudinal health trajectories that can support prompt recognition and inform associated early actions. However, relevant information is acquired at a different rate for each patient, and there is an inherent trade-off between the earliness versus the specificity of diagnosis and related actions. Therefore, determining when to alert providers about a likely chronic condition requires us to weigh the predicted risk at the given time against the anticipated value of future information. To address this challenge, we analyze the optimal timing of early alerts using a Partially Observable Markov Decision Process (POMDP) with asymmetric reward. To learn an optimal alerting policy, we then propose a model-free reinforcement learning (RL) framework tailored to long-term clinical event surveillance from EHRs. Our proposed framework overcomes the pervasive issue of right-censoring in offline EHRs by leveraging a pseudo-label imputation approach. We also analytically demonstrate that entropy-regularized RL enables post-hoc threshold calibration to adapt the learned policy to specific preferences regarding the importance of earliness versus specificity without retraining. Systematic evaluations in synthetic data reveal that the advantage of RL-based look-ahead planning is maximized when diagnostic evidence emerges in predictable information bursts. Finally, real-world validations on two clinical cohorts show that our policy achieves an actionable lead time of 20.9 months prior to Alzheimer's disease diagnosis and 8.7 months prior to autism diagnosis in a pediatric cohort, both at 90% specificity. Our method and results provide a generalizable blueprint for optimal surveillance of chronic disease processes.},
}

@article {pmid42820327,
year = {2026},
author = {Lin, Y and Cho, I and Zhu, X and Wang, K and Zhu, L and Wong, W and Murray, M and Zhou, F},
title = {Potential of Ginkgo biloba Extract to Intervene in Chronic Inflammation-Related Diseases.},
journal = {Phytotherapy research : PTR},
volume = {},
number = {},
pages = {},
doi = {10.1002/ptr.70467},
pmid = {42820327},
issn = {1099-1573},
support = {//USYD-Wepon and Faculty of Health and Medicine Scholarship of the University of Sydney/ ; },
abstract = {Chronic inflammation is a pathological mechanism of central importance that underpins a wide range of diseases, including neurodegenerative, cardiovascular, respiratory, gastrointestinal, and dermatological disorders. Ginkgo biloba extract (GBE), a standardized formulation derived from Ginkgo biloba leaves, has attracted growing attention due to its anti-inflammatory, antioxidant, and neuroprotective properties. This review comprehensively summarizes the current preclinical and clinical evidence regarding the therapeutic potential of GBE and its active constituents in inflammation-related diseases. GBE has been shown to attenuate pro-inflammatory cytokine production, suppress nuclear factor kappa B (NF-κB) activation, restore redox homeostasis, and modulate disease-relevant pathways in models of Alzheimer's disease, Parkinson's disease, multiple sclerosis, atherosclerosis, asthma, chronic obstructive pulmonary disease, inflammatory bowel disease, inflammatory skin conditions and rheumatoid arthritis. While these findings highlight the promising multi-targeted anti-inflammatory actions of GBE, limitations remain regarding the identification of specific active compounds, standardization of formulations, and the availability of robust clinical evidence. Further research is warranted to clarify the mechanisms of action and optimize delivery of GBE, and to validate the efficacy and safety of GBE in large-scale clinical trials.},
}

@article {pmid42820818,
year = {2026},
author = {Dillon, EC and Bailey, C and Alsamawi, A and Aasaavari, A and Fabian, T and Robison, J},
title = {"I Wanted to Get Back Out There": In-depth Interviews With Older Adults and Family Caregivers About Moving Out of Nursing Homes Using Medicaid's Money Follows the Person Program and How Dementia Influences Transitions.},
journal = {Journal of applied gerontology : the official journal of the Southern Gerontological Society},
volume = {},
number = {},
pages = {7334648261491313},
doi = {10.1177/07334648261491313},
pmid = {42820818},
issn = {1552-4523},
abstract = {Medicaid's Money Follows the Person (MFP) Program enables nursing home residents to return to community living, yet people living with dementia (PLWD) less often transition to the community through MFP, for unclear reasons. To understand mechanisms underlying this disparity, we conducted in-depth interviews with 44 older adults in Connecticut eligible for MFP and 44 family caregivers (41% PLWD/PLWD family members). Desire to move, program awareness, ability to self-advocate, personal care needs, family support, housing and home and community-based services (HCBS) resources all influenced moves. PLWD less often desired to move, typically required more assistance to move, were less able to self-advocate and manage logistics, had higher personal care needs, needed more family/informal support, and had additional safety and supervision needs. Better support for PLWD is needed in transition and HCBS programs as the population grows, nursing homes beds decrease, and the desire to live in the community persists.},
}

@article {pmid42820819,
year = {2026},
author = {Zhang, Q and Yu, J and Zhai, X and Zhang, L and Peng, J and Deng, C and Liu, Y and Zhou, Q and Niu, T and Luo, F and Chen, C},
title = {Mosaic Loss of the Y Chromosome: Mechanisms and Diseases.},
journal = {Protein & cell},
volume = {},
number = {},
pages = {},
doi = {10.1093/procel/pwag073},
pmid = {42820819},
issn = {1674-8018},
abstract = {Mosaic loss of the Y chromosome (mLOY) is a male‑specific somatic loss of the Y chromosome that is predominantly observed in peripheral blood leukocytes, but can also be found in other tissue types. It represents one of the most common male-specific somatic mutations, particularly prevalent in aging individuals. Accumulating evidence shows that mLOY markedly increases the incidence, progression, and adverse prognosis of multiple diseases, including, but not limited to, myocardial fibrosis, lung and bladder cancers, and Alzheimer's disease. Mechanistically, for extrinsic effects of mLOY, hematopoietic mLOY affect other cell populations, thereby promoting disease initiation and progression. From an intrinsic effects, mLOY within cells reprograms autosomal gene expression and reshapes interactions with the immune microenvironment, jointly driving malignant evolution. In this review, we summarize the current understanding of both intrinsic and extrinsic mLOY effects on immune regulation and disease pathogenesis, highlighting its multifaceted roles across cancer, cardiovascular disorders, infections, and other mLOY-associated conditions.},
}

@article {pmid42821427,
year = {2026},
author = {Lévesque, M and Akzam-Ouellette, MA and Joubert, S and Arguin, M},
title = {Altered temporal features of visual processing in subjective cognitive decline.},
journal = {Neuropsychology},
volume = {},
number = {},
pages = {},
doi = {10.1037/neu0001128},
pmid = {42821427},
issn = {1931-1559},
support = {//Hope for Dementia/ ; },
abstract = {OBJECTIVE: Subjective cognitive decline (SCD) is possibly the earliest known stage of Alzheimer's disease. Individuals with SCD report perceiving a decline in their cognitive functioning and express concern about it. However, when assessed with standard neuropsychological tests, they perform within normal limits.

METHOD: The present study focuses on the temporal features of visual processing in SCD using the random temporal sampling technique. This method reveals the perceptual oscillations which occur during a visual task by presenting stimuli with randomly varying signal-to-noise ratio through time. Fourteen individuals with SCD and 15 others without (i.e., controls), aged between 60 and 85 years old, took part in the study.

RESULTS: Participants with SCD performed within normal limits on neuropsychological tasks, as did the control group. In the experimental task, participants had to recognize briefly presented five-letter French words. The results take the form of classification images, which depict how visual processing efficiency fluctuates over time and across different frequency bands of signal-to-noise ratio oscillations. The classification images reveal significant differences between groups on the temporal patterns of visual processing. A machine learning classifier was used to categorize the data of individual participants according to group membership. The classifier achieved 79.3% classification accuracy using 18.0% of the available features.

CONCLUSIONS: Even though SCD individuals show no detectable cognitive impairment in neuropsychological testing, random temporal sampling can reveal anomalies in their perceptual function. (PsycInfo Database Record (c) 2026 APA, all rights reserved).},
}

@article {pmid42821606,
year = {2026},
author = {Xu, MY and Bai, YD and Zeng, XQ and Tan, CR and Lai, YJ and Wang, YJ},
title = {Bazedoxifene restores myelin changes and attenuates cognitive deficits in a mouse model of Alzheimer's disease.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261490479},
doi = {10.1177/13872877261490479},
pmid = {42821606},
issn = {1875-8908},
abstract = {BackgroundDemyelination and remyelination are critical processes in the pathogenesis of Alzheimer's disease (AD). The selective estrogen receptor modulator bazedoxifene (BZA) has been shown to promote remyelination, suggesting its potential therapeutic efficacy.ObjectiveThis study aimed to evaluate the therapeutic efficacy of BZA in addressing demyelination and associated cognitive deficits in a mouse model of AD.MethodsThe changes in myelin and oligodendrocyte-related indicators in the brains of APP/PS1 mice were assessed via immunostaining. 5 × FAD transgenic mice received oral administration of BZA or vehicle for 3 months. The therapeutic outcomes were evaluated through behavioral tests, immunostaining and western blotting.ResultsAD mice exhibited pronounced myelin loss and oligodendrocytes depletion. BZA treatment attenuated cognitive decline, restored myelin changes and mitigated neurodegeneration in the brain. These effects were observed independently of alterations in amyloid-β deposition.ConclusionsThese findings provide compelling evidence supporting the involvement of demyelination in AD and suggest that BZA may represent a promising therapeutic agent for AD by targeting myelin repair mechanisms.},
}

@article {pmid42821639,
year = {2026},
author = {Schwaninger, I and Ighanian, P and Borga, L and Giraitis, M and Hoogendoorn, P and Klucken, J},
title = {Value in app store metadata and user reviews: A dual perspective on quality of Parkinson's and dementia apps.},
journal = {PLOS digital health},
volume = {5},
number = {10},
pages = {e0001730},
pmid = {42821639},
issn = {2767-3170},
abstract = {App stores provide a range of health applications for people living with Alzheimer's disease (AD) and Parkinson's disease (PD). Users like patients can access information from both manufacturer-provided app descriptions and metadata, as well as from user reviews. However, navigating this information to identify value-generating apps of high quality remains challenging. From a health technology assessment (HTA) standpoint, quality is defined by evidence-based medicine, safety, and user-centeredness. To explore the potential value of app store information available to patients, we conducted a descriptive, mixed-methods analysis of unstructured app metadata and user feedback from the Apple App Store and Google Play Store (as of May 2024). We analyzed 1,237 AD/PD-related apps which included 50 duplicates (resulting in 1,187 apps), utilizing descriptive statistics, content analysis, large language model-supported exploratory classification, and a topic modeling approach. In total, only about 2% of the apps claimed to be certified medical devices. Moreover, 24% of Apple apps and 14% of Google apps were in the "Medical" app store genre, among which we found that 63% of Apple and 54% of Google apps were patient-facing. We manually categorized patient-facing apps predominantly under "Care Support," followed by "Health & Wellness" and "Patient Monitoring." Importantly, user feedback provided exploratory, potentially valuable patient-reported outcome and experience information but is derived from personal opinions on "user experience," "health improvement," and "costs." As quality information on DHTs could be identified in unstructured app metadata, this information should be improved in trustworthiness and more accessible to users like patients, supporting the public to find high-quality health apps. Furthermore, as user opinions contained information with potential value for patients, these should be explored as complementary value-generating indicators of health apps in future work.},
}

@article {pmid42821808,
year = {2026},
author = {Costa, N and Marcélo Fleuret, C and Gombault, E and Soto Martin, M and De Mauleon, A},
title = {Longitudinal Impact of Agitation and Aggression Symptoms on Societal Costs in Alzheimer's Disease: A Focus on Informal Care and Socioeconomic Disparities.},
journal = {International journal of geriatric psychiatry},
volume = {41},
number = {10},
pages = {e70257},
pmid = {42821808},
issn = {1099-1166},
support = {//Ethypharm/ ; //Center Hospitalier Universitaire de Toulouse/ ; },
mesh = {Humans ; Female ; Male ; *Alzheimer Disease/economics/psychology ; Aged ; *Psychomotor Agitation/economics ; *Aggression/psychology ; France ; Longitudinal Studies ; Prospective Studies ; Aged, 80 and over ; Caregivers/economics ; *Cost of Illness ; Middle Aged ; *Health Care Costs/statistics & numerical data ; Socioeconomic Disparities in Health ; *Patient Care/economics ; Long-Term Care/economics ; },
abstract = {BACKGROUND: To date, no longitudinal study has assessed the effect of agitation on societal costs-particularly informal care costs-over time in Alzheimer's Disease (AD) patients with Agitation and Aggression (A/A) symptoms.

OBJECTIVES: This study estimates the impact of A/A symptoms evolution on longitudinal care costs including informal care costs in moderate-to-severe AD, considering patient and caregiver socioeconomic characteristics.

DESIGN: A longitudinal trajectory clustering method was used on this longitudinal, prospective, multicenter observational cohort study.

SETTING AND PARTICIPANTS: 262 community-dwelling and long-term care facility (LTCF) patients of both sexes, aged 60 years and older, with clinically significant A/A symptoms were recruited from memory centers in southwest France.

METHODS: Patients were followed for 12 months. A/A data was recorded by clinicians using the Neuropsychiatric Inventory (NPI-c). Costs were estimated from a societal perspective, including healthcare and informal care, using the RUD questionnaire. K-means longitudinal method identified A/A evolution profiles. Cost differences across A/A evolution profiles were analyzed using Generalized Linear Models.

RESULTS: Two A/A evolution profiles were identified: mild symptoms at baseline with improvement (A) and moderate symptoms at baseline with limited improvement or stability (B). Annual costs were €22,959 in group A and €23,625 in group B excluding supervision, and €52,111 and €56,149, respectively, including supervision. In LTCF residents, higher A/A severity was associated with increased medical visits and medication costs, though overall cost differences were smaller. Informal care neared 70% of total costs for community-dwelling patients, with supervision covering the majority of these costs.

CONCLUSIONS: Evolution of A/A symptoms significantly increases both healthcare and informal care costs, particularly in at-home settings. Integrating systematic monitoring of behavioral symptoms into routine care would enable personalized, cost-effective strategies. Informal care costs, often undervalued and overlooked in economic analyzes, underscores the need for improvement in resource allocation and quality of life, for both patients and caregivers.

CLINICAL TRIAL NUMBER: NCT03554226.},
}

Humans
Female
Male
*Alzheimer Disease/economics/psychology
Aged
*Psychomotor Agitation/economics
*Aggression/psychology
France
Longitudinal Studies
Prospective Studies
Aged, 80 and over
Caregivers/economics
*Cost of Illness
Middle Aged
*Health Care Costs/statistics & numerical data
Socioeconomic Disparities in Health
*Patient Care/economics
Long-Term Care/economics

@article {pmid42821845,
year = {2026},
author = {Shir, D and Algeciras-Schimnich, A and Piura, YD and Bornhorst, JA and Figdore, DJ and Elgenidi, A and Lachner, C and Graff-Radford, NR and Day, GS},
title = {Clinical Factors Associated With Discordant Plasma P-Tau217 and Established Alzheimer Disease Biomarkers.},
journal = {Neurology},
volume = {107},
number = {8},
pages = {e218591},
doi = {10.1212/WNL.0000000000218591},
pmid = {42821845},
issn = {1526-632X},
mesh = {Humans ; *tau Proteins/blood ; *Alzheimer Disease/blood/diagnosis ; Female ; Biomarkers/blood ; Male ; Retrospective Studies ; Aged ; Amyloid beta-Peptides/cerebrospinal fluid/blood ; Aged, 80 and over ; Middle Aged ; Phosphorylation ; Positron-Emission Tomography ; },
abstract = {BACKGROUND AND OBJECTIVES: Plasma phosphorylated tau (p-tau) 217 is increasingly used for Alzheimer disease (AD) diagnosis and treatment decisions but may be discordant with established AD biomarkers. False-positive (FP) plasma results may lead to overtreatment and false-negative (FN) results to missed or delayed disease-modifying therapies. We evaluated factors associated with discordant results.

METHODS: This retrospective study included participants enrolled in memory and aging studies at Mayo Clinic with "positive" (>0.324 pg/mL) or "negative" (<0.186 pg/mL) plasma p-tau217 results and confirmatory AD biomarkers. Plasma results were classified as true positive (TP), true negative (TN), FP, or FN, referencing amyloid-PET and CSF p-tau181/β-amyloid (Aβ) 42. Clinical and laboratory variables were compared using univariate analyses; multivariable logistic regression evaluated independent associations with discordance.

RESULTS: Among 706 participants (median 70.0 [interquartile range 15.8] years; 54% male), 60 (8.5%) had discordant plasma p-tau217 results. FN results (5.6%) were more frequent than FP results (2.8%; p = 0.007). Discordance was associated with older age (odds ratio [OR] 1.61 per decade, 95% CI 1.23-2.14) and obstructive sleep apnea (OR 1.94, 95% CI 1.08-3.49). FN (vs TP) results were associated with milder clinical stage (global Clinical Dementia Rating [CDR] ≤0.5 vs CDR ≥1; p < 0.001), higher Mini-Mental State Examination scores (OR 1.20 per point, 95% CI 1.05-1.36), obstructive sleep apnea (OR 2.01, 95% CI 1.01-4.3), higher body mass index (OR 1.11/kg/m[2], 95% CI 1.03-1.20), and higher estimated glomerular filtration rate (eGFR: OR 1.33/10 mL/min/1.73 m[2], 95% CI 1.05-1.69). In age-adjusted models, body mass index (OR 1.14, 95% CI 1.03-1.25), eGFR (OR 1.63/10 mL/min/1.73 m[2], 95% CI 1.22-2.16), and earlier clinical stage (CDR ≤0.5) were independently associated with FN results. FP (vs TN) results were associated with older age (OR 2.37, 95% CI 1.36-4.09), thyroid disease (OR 4.41, 95% CI 1.36-14.3), lower eGFR (OR 0.48/10 mL/min/1.73 m[2], 95% CI 0.31-0.66), and advanced disease stage (CDR ≥1). In age-adjusted models, eGFR (OR 0.54/10 mL/min/1.73 m[2], 95% CI 0.35-0.82) and advanced disease stage (CDR ≥ 1 vs CDR 0: OR 11.11, 95% CI 2.0-50.0; vs CDR 0.5: OR 4.55, 95% CI 1.12-16.67) were independently associated with FP results.

DISCUSSION: Plasma p-tau217 results and established AD biomarkers were discordant in 8.5% of participants. Clinical stage and factors related to brain amyloid clearance, renal clearance, and volume of distribution were associated with discordant results. These insights may inform mechanisms of discordance and identify patients requiring confirmatory biomarker measures.},
}

Humans
*tau Proteins/blood
*Alzheimer Disease/blood/diagnosis
Female
Biomarkers/blood
Male
Retrospective Studies
Aged
Amyloid beta-Peptides/cerebrospinal fluid/blood
Aged, 80 and over
Middle Aged
Phosphorylation
Positron-Emission Tomography

@article {pmid42821881,
year = {2026},
author = {Güntert, L and Taeymans, J and Baur, H and Van Dyck, M and Lutz, N},
title = {Physical inactivity attributable burden of disease on morbidity and mortality across Swiss language regions: a population-based modelling study.},
journal = {Swiss medical weekly},
volume = {156},
number = {},
pages = {5162},
doi = {10.57187/5162},
pmid = {42821881},
issn = {1424-3997},
mesh = {Humans ; Switzerland/epidemiology ; Female ; *Sedentary Behavior ; Male ; Middle Aged ; Aged ; Adult ; *Cost of Illness ; Prevalence ; Language ; Risk Factors ; *Noncommunicable Diseases/epidemiology ; Morbidity ; Exercise ; },
abstract = {UNLABELLED: BACKGROUND: Physical inactivity is a major risk factor for noncommunicable diseases, contributing to both substantial morbidity and premature mortality. In Switzerland, the prevalence of physical inactivity varies across language regions. This study aimed to quantify differences across Swiss language regions in the physical inactivity-attributable burden of disease, expressed as Years Lived with Disability (YLD) and Years of Life Lost (YLL) for 2022. The analysis focuses on YLD and YLL attributable to physical inactivity across 15 physical inactivity-associated diseases.

METHODS: This study employed the Population Attributable Fraction approach to estimate the proportion of YLD and YLL attributable to physical inactivity in Switzerland. The analysis included individuals aged >20 years and was stratified by disease, age, sex and language region (German-, French- and Italian-speaking). Physical inactivity was defined according to WHO guidelines as not meeting at least 150 minutes of moderate or 75 minutes of vigorous physical activity per week. Prevalence data on physical inactivity were derived from the 2022 Swiss Health Survey. Prevalences were combined with relative risks (RR) of corresponding diseases, identified through a systematic literature search to derive Population Attributable Fractions. Estimates of YLD and YLL for Switzerland for 2022 were derived from the Global Burden of Disease study. YLD and YLL estimates attributable to physical inactivity are presented as rates per 100,000 people aged >20 years. Uncertainty was assessed using parametric bootstrapping.

RESULTS: Overall, the physical inactivity-attributable burden of disease was estimated at 227.08 (95% CI: 214.74-240.08) YLD and 424.23 (95% CI: 383.15-479.23) YLL per 100,000 people aged >20 years. This corresponds to approximately 2% of total DALYs in Switzerland in 2022. Clear regional differences were observed. Estimated physical inactivity-attributable YLD rates were highest in the Italian-speaking region (134.90; 95% CI: 122.04-148.25) followed by the French-speaking region (130.72; 95% CI: 120.78-141.50) and German-speaking region (96.26; 95% CI: 88.81-104.01). Similarly, estimated YLL rates attributable to physical inactivity were highest in the Italian-speaking region (287.74; 95% CI: 245.82-349.99), followed by the French-speaking region (221.56; 95% CI: 192.54-264.55) and German-speaking region (186.67; 95% CI: 162.64-222.27). Disease-specific analysis indicated that depression (93.38; 95% CI: 85.46-101.80) and low back pain (52.01; 95% CI: 45.90-58.47) contributed most to physical inactivity-attributable YLD rates, whereas coronary heart disease (132.12; 95% CI: 115.60-149.55) and Alzheimer's disease and dementia (83.61; 95% CI: 51.90-134.97) were the main contributors to physical inactivity-attributable YLL rates. Women showed consistently higher burden of disease than men, with physical inactivity-attributable YLD rates of 286.06 (95% CI: 264.58-308.90) versus 166.32 (95% CI: 155.06-178.44) and physical inactivity-attributable YLL rates of 475.23 (95% CI: 404.85-577.64) versus 371.69 (95% CI: 337.50-414.96).

CONCLUSION: Results of this analysis suggest that physical inactivity significantly contributes to YLD and YLL rates in Switzerland, with pronounced regional and sex-specific disparities. The higher burden of disease observed in the Italian- and French-speaking regions highlights the need for regionally tailored prevention strategies that address cultural and contextual differences.},
}

Humans
Switzerland/epidemiology
Female
*Sedentary Behavior
Male
Middle Aged
Aged
Adult
*Cost of Illness
Prevalence
Language
Risk Factors
*Noncommunicable Diseases/epidemiology
Morbidity
Exercise

@article {pmid42822260,
year = {2026},
author = {d'Orsi, G},
title = {Epilepsy phenotypes and Alzheimer's disease biomarkers in adults with down syndrome: beyond diagnostic codes.},
journal = {Seizure},
volume = {143},
number = {},
pages = {39-40},
doi = {10.1016/j.seizure.2026.09.024},
pmid = {42822260},
issn = {1532-2688},
}

@article {pmid42822579,
year = {2026},
author = {Zhang, X and Tao, T and Liu, W and Xie, A and Liang, Y and Zhu, X},
title = {Mitochondria and associated complexes as therapeutic targets in aging: From biomacromolecular structure-function insights to clinical translation.},
journal = {Mitochondrion},
volume = {},
number = {},
pages = {102221},
doi = {10.1016/j.mito.2026.102221},
pmid = {42822579},
issn = {1872-8278},
abstract = {Mitochondria and their biomacromolecular complexes-such as the electron transport chain (ETC), mitochondrial permeability transition pore (mPTP), and protein quality control systems-play pivotal roles in aging and age-related diseases. This review integrates recent insights into how structural and functional disruptions of these complexes drive cellular senescence and systemic decline. We outline the architecture of mitochondrial assemblies (e.g., oxidative phosphorylation (OXPHOS) complexes, mtDNA-protein interactions) essential for energy production and organelle stability. Age-related alterations in stoichiometry, conformational states (e.g., mPTP opening), and post-translational modifications (e.g., SIRT3-mediated acetylation) compromise mitochondrial integrity, fueling metabolic dysfunction and chronic inflammation ("inflammaging"). Therapeutic strategies include small-molecule stabilizers of ETC supercomplexes, peptide-based mPTP inhibitors, and CRISPR-mediated correction of mtDNA-protein mismatches. Tissue-specific models (e.g., Complex I in skin aging, Bcl-2 protein imbalance in ovarian aging) exemplify the clinical relevance. We also categorize nine age-associated diseases-neurodegenerative, cardiovascular, and cancer types-based on their dependence on distinct mitochondrial complexes, such as ATP synthase in cancer resistance and the TIM/TOM import machinery in Alzheimer's disease. By linking structural findings (e.g., cryo-EM studies) with therapeutic innovation, this review offers a framework for targeting mitochondrial complexes to mitigate aging and its related pathologies.},
}

@article {pmid42822589,
year = {2026},
author = {Saleki, S and Wabant, C and Loriot, A and Stanga, S and Masquelier, J and Muccioli, GG and Suelves, N and Kienlen-Campard, P},
title = {Alzheimer's disease-associated presenilin 2 N141I mutation impairs neuronal lipid homeostasis and mitochondrial dynamics through selective downregulation of the Golgi exchange factor Gbf1.},
journal = {Experimental neurology},
volume = {},
number = {},
pages = {116045},
doi = {10.1016/j.expneurol.2026.116045},
pmid = {42822589},
issn = {1090-2430},
abstract = {Presenilin 2 (PS2) mutations cause familial Alzheimer's disease, yet their effects beyond amyloid processing remain poorly understood. Here, we investigated how PS2 deletion and the N141I mutation affect neuronal lipid homeostasis and mitochondrial dynamics in mouse primary neurons. Both PS2 deletion and N141I mutation reduced neuronal lipid content. However, exogenous lipid supplementation rescued this deficit only in N141I-expressing neurons, indicating a partial loss-of-function effect. N141I neurons also displayed reduced OPA1, a mitochondrial fusion regulator, restored by lipid supplementation. RNA-sequencing identified Gbf1, a Golgi-specific guanine nucleotide exchange factor, as selectively downregulated in N141I but not knockout tissue, which was confirmed at the protein level in mouse brain and primary neurons. Gbf1 knockdown in mouse embryonic fibroblasts (MEFs) recapitulated the N141I lipid profile. Together, these findings reveal a PS2-GBF1-lipid-mitochondria axis disrupted specifically by the N141I mutation, suggesting an amyloid-independent pathway contributing to neurodegeneration and identifying potential therapeutic targets for familial Alzheimer's disease.},
}

@article {pmid42822590,
year = {2026},
author = {Yagihara, H and Saito, Y and Takeuchi, T and Seki, K and Minakawa, EN},
title = {Fluid amyloid-β (Aβ) biomarkers reflect early β-sheet-rich Aβ deposition during the preclinical stage in Alzheimer's disease model 5XFAD mice.},
journal = {Experimental neurology},
volume = {},
number = {},
pages = {116044},
doi = {10.1016/j.expneurol.2026.116044},
pmid = {42822590},
issn = {1090-2430},
abstract = {Early detection of disease progression using clinically-relevant biomarkers in animal models is important for mechanistic studies and for developing therapeutics in neurodegenerative diseases including Alzheimer's disease (AD). The preclinical stage of AD, when amyloid-β (Aβ) starts to accumulate before cognitive decline, provides a critical window for disease modification. In humans, decreases in cerebrospinal fluid (CSF) Aβ42 and the Aβ42/Aβ40 ratio in preclinical AD are considered to reflect the preferential sequestration of aggregation-prone Aβ42 into β-sheet-rich deposition in the brain, with corresponding changes being detectable in plasma. However, the extent to which these biomarker-pathology relationships are recapitulated in AD model mice remains incompletely defined. Here we show that CSF and plasma Aβ42 and the Aβ42/Aβ40 ratio decline with age in parallel with the progression of β-sheet-rich Aβ deposition in preclinical 5XFAD mice, one of the most widely used AD mouse models, as assessed through monthly profiling of these biomarkers. Notably, the CSF Aβ42/Aβ40 ratio showed a negative correlation with β-sheet-rich Aβ deposition in the brain, whereas CSF Aβ40 did not show a comparable association. In addition, the plasma Aβ42/Aβ40 ratio showed a positive correlation with the CSF Aβ42/Aβ40 ratio, suggesting that the plasma Aβ42/Aβ40 ratio may also reflect brain Aβ deposition in this model. The strength of these correlations differed by sex, suggesting that sex-dependent differences in the Aβ kinetics in this model may influence how closely fluid biomarkers reflect pathological progression. These findings support the potential utility of fluid Aβ as a pathology-linked, translatable biomarker in preclinical 5XFAD mice.},
}

@article {pmid42822610,
year = {2026},
author = {Arayesh, MJ and Ataellahi, F and Masoudi, R},
title = {Differential effects of amyloid-β and tau on UCH gene expression in Drosophila models of Alzheimer's disease.},
journal = {Gene},
volume = {},
number = {},
pages = {150431},
doi = {10.1016/j.gene.2026.150431},
pmid = {42822610},
issn = {1879-0038},
abstract = {BACKGROUND: Alzheimer's disease (AD) is a common neurodegenerative disorder characterized by progressive impairments in learning and memory. Substantial evidence indicates that dysfunction of the ubiquitin-proteasome system (UPS) in the AD brain leads to aberrant protein aggregation, ultimately resulting in synaptic dysfunction and neuronal loss. In this study, we investigated the effects of pan-neuronal expression of Tau[WT] or Aβ42-key pathological hallmarks of AD-on the expression of UCH, a critical UPS component, in Drosophila melanogaster at three time points: 5, 15, and 25 days after eclosion.

METHODS AND RESULTS: UCH mRNA levels were quantified using real-time RT-PCR. UCH expression showed an age-dependent downregulation in Aβ42 transgenic flies over all three post-eclosion intervals. While UCH transcription witnessed no significant change in 5-day-old Tau[WT] transgenic flies, there was a considerable decline in UCH mRNA levels in 15- and 25-day-old flies. Notably, Aβ42 had a more prominent impact on UCH gene expression than Tau[WT] across all three time points.

CONCLUSION: Tau[WT] and Aβ42 exert independent adverse effects on UCH expression. An apparent age-related trend was observed in the fly models, whereby Aβ42 showed a relatively stronger influence on UCH transcription compared with Tau[WT]. Accordingly, therapeutic strategies that target both Tau and amyloid-β may warrant consideration.},
}

@article {pmid42822752,
year = {2026},
author = {Xuan, Z and Rahman, MU and Ilyas, M and Alioui, Y and Xin, Y and Cao, X and Ullah, H},
title = {Gut bacterial isolates from individuals with Alzheimer's disease induce strain-specific intestinal, inflammatory, and neurobehavioral phenotypes in mice.},
journal = {Brain research},
volume = {},
number = {},
pages = {150569},
doi = {10.1016/j.brainres.2026.150569},
pmid = {42822752},
issn = {1872-6240},
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder in which alterations in the microbiota-gut-brain axis has been increasingly investigated. However, the effects of individual cultivable bacterial isolates recovered from individuals with AD on host intestinal and neurobehavioral phenotypes remain insufficiently characterized. In this study, three bacterial isolates, Escherichia coli, Klebsiella pneumoniae, and Citrobacter pasteurii, were recovered from fecal samples collected from individuals diagnosed with AD and evaluated in healthy BALB/c mice following long-term oral administration. The effects of the isolates on physiological parameters, intestinal morphology and barrier-associated markers, inflammatory responses, gut microbial community composition, and neurobehavioral outcomes were assessed. The three isolates produced strain-specific effects, with C. pasteurii producing the most pronounced overall phenotype. Mice receiving C. pasteurii showed reduced body weight gain, increased spleen index, and shortened colon length, accompanied by elevated circulating inflammatory cytokines. Alterations in goblet cells, MUC2 expression, and tight-junction-associated proteins, including ZO-1 and claudin-1, were also observed, indicating alterations in intestinal barrier-associated structures. Gut microbiota analysis revealed strain-specific changes in microbial diversity and community composition, with the most pronounced alterations observed in the C. pasteurii group. In addition, C. pasteurii administration was associated with increased hippocampal inflammatory responses and astrocytic activation, whereas no apparent hippocampal neuronal loss was detected. Neurobehavioral testing revealed reduced locomotor activity and altered exploratory and behavioral responses, particularly in the C. pasteurii group. However, because reduced locomotor activity may influence performance in the novel object recognition and tail suspension tests, these findings should be interpreted cautiously. K. pneumoniae produced intermediate effects, whereas E. coli showed comparatively limited effects under the experimental conditions used. Collectively, these findings indicate that the tested bacterial isolates recovered from individuals with AD can produce strain-specific intestinal, inflammatory, microbial, and neurobehavioral alterations in healthy mice, with C. pasteurii producing the strongest overall phenotype. Importantly, the observed changes in gut microbial composition do not establish specific bacterial functions or pathogenicity, as microbial functional activity was not directly assessed. The present study does not establish that these bacteria are specifically associated with AD or that they cause AD progression; rather, it provides experimental evidence that individual cultivable bacterial isolates recovered from individuals with AD may differentially influence host phenotypes relevant to processes implicated in neurodegenerative disease. Further studies using larger human cohorts with appropriate healthy controls, validated AD models, and direct functional and mechanistic investigations are required to clarify the relevance of these observations to AD pathophysiology.},
}

@article {pmid42823347,
year = {2026},
author = {Bravo-Risi, F and Alburquerque Orta, G and Kim, PJ and Wylie-Young, H and Stimming, TH and Soto, P and Estrada, L and Jankowsky, JL and Morales, R},
title = {The Progression of Prion Diseases Is Not Altered in the Absence of TMEM106B.},
journal = {eNeuro},
volume = {13},
number = {10},
pages = {},
doi = {10.1523/ENEURO.0043-26.2026},
pmid = {42823347},
issn = {2373-2822},
mesh = {Animals ; *Membrane Proteins/genetics/deficiency/metabolism ; Female ; *Nerve Tissue Proteins/genetics/deficiency/metabolism ; Male ; Disease Progression ; *Prion Diseases/pathology/metabolism/genetics ; Disease Models, Animal ; Prions/metabolism ; Mice, Knockout ; Brain/pathology/metabolism ; Mice, Inbred C57BL ; Mice ; },
abstract = {Transmembrane protein 106B (TMEM106B) is a type II transmembrane glycoprotein localized in late endosomes and lysosomes. This protein has been attributed to relevant roles in disease risk and progression of multiple neurodegenerative disorders. In experimental models, TMEM106B has been linked with the prion-like spread of misfolded tau proteins responsible for Alzheimer's disease and other tauopathies. The role of this protein in the spread of other misfolded proteins, like prions, has not been explored. Here, we tested whether the removal of TMEM106B altered the progression of prion diseases using animal mouse models (male and female). This was carefully tested using different prion dosages, strains, and routes of administration. Our results demonstrate that the absence of TMEM106B does not alter the progression of prion diseases in any of the tested conditions. This data provides supportive evidence on the specificity of TMEM106B in neurodegenerative conditions.},
}

Animals
*Membrane Proteins/genetics/deficiency/metabolism
Female
*Nerve Tissue Proteins/genetics/deficiency/metabolism
Male
Disease Progression
*Prion Diseases/pathology/metabolism/genetics
Disease Models, Animal
Prions/metabolism
Mice, Knockout
Brain/pathology/metabolism
Mice, Inbred C57BL
Mice

@article {pmid42823476,
year = {2026},
author = {Rittmo, J and Franzmeier, N and Strandberg, O and Chauveau, L and Satterthwaite, TD and Wisse, LEM and Spotorno, N and Behjat, HH and Dehsarvi, A and van Westen, D and Anijärv, TE and , and Landau, SM and Palmqvist, S and Janelidze, S and Stomrud, E and Ossenkoppele, R and Mattsson-Carlgren, N and Hansson, O and Vogel, JW},
title = {Different functional connectivity gradients reflect aging and Alzheimer's disease.},
journal = {Nature neuroscience},
volume = {},
number = {},
pages = {},
pmid = {42823476},
issn = {1546-1726},
support = {KAW 2020.0239//Science for Life Laboratory (SciLifeLab)/ ; KAW 2020.0239//Science for Life Laboratory (SciLifeLab)/ ; 2024-03642//Vetenskapsrådet (Swedish Research Council)/ ; 2022-00775, 2021-02219//Vetenskapsrådet (Swedish Research Council)/ ; 2022-00775, 2021-02219//Vetenskapsrådet (Swedish Research Council)/ ; 2022-00775, 2021-02219//Vetenskapsrådet (Swedish Research Council)/ ; 2022-00775, 2021-02219//Vetenskapsrådet (Swedish Research Council)/ ; 2022-00775, 2021-02219//Vetenskapsrådet (Swedish Research Council)/ ; 2022-00775, 2021-02219//Vetenskapsrådet (Swedish Research Council)/ ; 2022-00775, 2021-02219//Vetenskapsrådet (Swedish Research Council)/ ; 2022-00775, 2021-02219//Vetenskapsrådet (Swedish Research Council)/ ; 2022-00775, 2021-02219//Vetenskapsrådet (Swedish Research Council)/ ; 2022-00775, 2021-02219//Vetenskapsrådet (Swedish Research Council)/ ; 2024-03642//Vetenskapsrådet (Swedish Research Council)/ ; 23074CB//Alzheimer Forschung Initiative (Alzheimer Forschung Initiative e.V.)/ ; 2022-0231//Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation)/ ; 2022-0231//Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation)/ ; 2022-0231//Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation)/ ; 2022-0231//Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation)/ ; 2022-0231//Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation)/ ; 2022-0231//Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation)/ ; 2022-0231//Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation)/ ; 2022-0231//Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation)/ ; 2022-0231//Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation)/ ; 2022-0231//Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation)/ ; ZEN24-1069572, SG-23-1061717/ALZ/Alzheimer's Association/United States ; ZEN24-1069572, SG-23-1061717/ALZ/Alzheimer's Association/United States ; ZEN24-1069572, SG-23-1061717/ALZ/Alzheimer's Association/United States ; ZEN24-1069572, SG-23-1061717/ALZ/Alzheimer's Association/United States ; ZEN24-1069572, SG-23-1061717/ALZ/Alzheimer's Association/United States ; ZEN24-1069572, SG-23-1061717/ALZ/Alzheimer's Association/United States ; ZEN24-1069572, SG-23-1061717/ALZ/Alzheimer's Association/United States ; ZEN24-1069572, SG-23-1061717/ALZ/Alzheimer's Association/United States ; ZEN24-1069572, SG-23-1061717/ALZ/Alzheimer's Association/United States ; ZEN24-1069572, SG-23-1061717/ALZ/Alzheimer's Association/United States ; ZEN24-1069572, SG-23-1061717/ALZ/Alzheimer's Association/United States ; FO2021-0293, FO2023-0163//Hjärnfonden (Swedish Brain Foundation)/ ; FO2021-0293, FO2023-0163//Hjärnfonden (Swedish Brain Foundation)/ ; FO2021-0293, FO2023-0163//Hjärnfonden (Swedish Brain Foundation)/ ; FO2021-0293, FO2023-0163//Hjärnfonden (Swedish Brain Foundation)/ ; FO2021-0293, FO2023-0163//Hjärnfonden (Swedish Brain Foundation)/ ; FO2021-0293, FO2023-0163//Hjärnfonden (Swedish Brain Foundation)/ ; FO2021-0293, FO2023-0163//Hjärnfonden (Swedish Brain Foundation)/ ; FO2021-0293, FO2023-0163//Hjärnfonden (Swedish Brain Foundation)/ ; FO2021-0293, FO2023-0163//Hjärnfonden (Swedish Brain Foundation)/ ; FO2021-0293, FO2023-0163//Hjärnfonden (Swedish Brain Foundation)/ ; FO2021-0293, FO2023-0163//Hjärnfonden (Swedish Brain Foundation)/ ; },
abstract = {Aging and Alzheimer's disease (AD) are accompanied by alterations to large-scale communication patterns in the brain, which can be tracked in vivo using functional connectivity. The location, direction and relevance of these changes remain widely debated, although they are rarely studied in the context of whole-cortex communication dynamics. Here, in two independent cohorts (BioFINDER-2, N = 973; Alzheimer's Disease Neuroimaging Initiative, N = 129), we show that functional connectivity changes associated with aging and AD are strongly aligned with separate fundamental axes of hierarchical brain communication. Early accumulation of AD pathology and subsequent cognitive decline are both linked to functional change along the sensory-association axis. Meanwhile, age-related functional changes occur along the representation-executive axis consistently throughout the adult lifespan. These findings together suggest that both AD and aging alter major but orthogonal functional pathways in the brain. More broadly, our findings position whole-brain connectivity dynamics as a unifying framework for interpreting functional changes across the adult lifespan.},
}

@article {pmid42823573,
year = {2026},
author = {Nguyen, N and Yuan, M and Wang, Y},
title = {From Design to Bedside: Brain-Targeted Engineered Nanoparticles and Predictive Modeling for Neurodegenerative Diseases Therapeutics.},
journal = {Pharmaceutical research},
volume = {},
number = {},
pages = {},
pmid = {42823573},
issn = {1573-904X},
support = {CMMI 1851635//National Science Foundation/ ; ECCS 2021081//National Science Foundation/ ; },
abstract = {Nanoparticle (NP)-based drug delivery systems offer promising solutions for neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's, which have no cure due to the brain's structural complexity and the restrictive nature of the blood-brain barrier (BBB). Conventional therapeutics, despite strong in vitro efficacy, often fail clinically due to poor brain penetration. Recent advances in NP engineering, including optimization of size (10-100 nm), surface charge (-10 to -20 mV), and targeted ligand decoration, have improved BBB crossing and reduced premature clearance. In parallel, predictive in silico approaches, such as physiologically based pharmacokinetic (PBPK) modeling, computational fluid dynamics, and machine learning models, enable quantitative prediction of NP biodistribution, residence times, and region-specific uptake. By simulating key determinants, including blood flow dynamics, vasculature heterogeneity, permeability, and retention, these computational tools accelerate lead selection, reduce experimental burden, and inform design before in vivo testing. This review integrates recent progress in NP design with advanced computational modeling, highlighting how their convergence provides a rational framework for developing next-generation brain-targeted therapeutics. We further discuss regulatory and translational challenges, including safety, biocompatibility, and the need for humanized preclinical benchmarks. Together, these innovations offer a roadmap for advancing NP-based strategies toward clinical impact in neurodegenerative disease.},
}

@article {pmid42823667,
year = {2026},
author = {Kavlak, Y and Yıldız, S and Yıldız, P and Kar, F},
title = {Effects of an eight-week combined exercise program on functional and sarcopenia-related outcomes in institutionalized older adults with and without Alzheimer's disease: a comparative intervention study.},
journal = {BMC geriatrics},
volume = {26},
number = {1},
pages = {},
pmid = {42823667},
issn = {1471-2318},
mesh = {Humans ; *Sarcopenia/therapy/physiopathology/psychology/diagnosis/epidemiology ; Aged ; Female ; Male ; *Alzheimer Disease/therapy/psychology/physiopathology/diagnosis/epidemiology ; Aged, 80 and over ; Muscle Strength/physiology ; *Exercise Therapy/methods ; Treatment Outcome ; *Institutionalization/trends/methods ; Activities of Daily Living/psychology ; Time Factors ; Nutritional Status ; },
abstract = {BACKGROUND: Alzheimer's disease (AD) is a major cause of disability in older adults and is frequently accompanied by sarcopenia and functional decline, contributing to loss of independence. To investigate the effects of an eight-week combined exercise program on physical and cognitive function, sarcopenia-related outcomes and nutritional status in institutionalized older adults with and without AD.

METHODS: Twenty-three participants aged ≥ 65 years (12 with moderate AD and 11 cognitively healthy controls) completed supervised combined aerobic and resistance exercise three times per week for eight weeks. Muscle strength, physical performance, nutritional status, cognition, and activities of daily living were assessed before and after the intervention. Sarcopenia status was classified according to Working Group on Sarcopenia in Older People 2018 (EWGSOP2) criteria using strength and gait speed measures.

RESULTS: Comparison of quadriceps muscle strength before and after exercise showed significant improvement in both Alzheimer's patients (p = 0.013) and the healthy group (p < 0.001). Significant improvement was found in MNA values ​​after exercise in Alzheimer's patients (p = 0.021) and in instrumental activities of daily living in healthy individuals (p = 0.002). After the intervention, quadriceps strength improved significantly in both groups (p < 0.001). When the relationships between parameters were examined, it was found that the relationships between physical function and daily living activities were significant in individuals with Alzheimer's disease (p < 0.05).

CONCLUSIONS: Short-term combined exercise is a versatile intervention method applicable to improve muscle strength, mobility, and nutritional status in older adults living in institutions, including those with Alzheimer's disease.},
}

Humans
*Sarcopenia/therapy/physiopathology/psychology/diagnosis/epidemiology
Aged
Female
Male
*Alzheimer Disease/therapy/psychology/physiopathology/diagnosis/epidemiology
Aged, 80 and over
Muscle Strength/physiology
*Exercise Therapy/methods
Treatment Outcome
*Institutionalization/trends/methods
Activities of Daily Living/psychology
Time Factors
Nutritional Status

@article {pmid42823730,
year = {2026},
author = {Rotter, J and Kirmann, T and Brendler, J and Anthofer, L and Wilpert, NM and Hallermann, S and Biebermann, H and Bechmann, I},
title = {Multiscale characterization and distribution of the thyroid hormone transporter MCT8 in the adult and aged human brain.},
journal = {Acta neuropathologica communications},
volume = {14},
number = {1},
pages = {},
pmid = {42823730},
issn = {2051-5960},
mesh = {Humans ; *Monocarboxylic Acid Transporters/metabolism/genetics ; Symporters ; Aged ; *Brain/metabolism/pathology ; Female ; Male ; Adult ; Middle Aged ; *Aging/metabolism/pathology ; *Thyroid Hormones/metabolism ; Aged, 80 and over ; },
abstract = {The local availability of thyroid hormones (TH) depends on TH transporters such as monocarboxylate transporter 8 (MCT8, encoded by SLC16A2). Mutations of SLC16A2 cause Allan-Herndon-Dudley syndrome (AHDS), a disorder characterized by severe neurodevelopmental and motor deficits. While MCT8's importance in foetal brain development is well-established, its precise topographical, cellular, and subcellular distribution in the adult human brain has remained largely uncharacterized, limiting our understanding of which structures depend on MCT8-mediated TH transport throughout life and whether neurodegenerative processes such as Alzheimer's disease (AD) affect local transporter availability. In this study, we systematically mapped MCT8 expression across eight functionally distinct brain regions from 14 aged human body donors. Our multiscale approach combined immunostaining, automated whole-slide image analysis of over 13 million cells, multiplex RNAscope in situ hybridization, stimulated emission depletion (STED) microscopy, and single-nucleus RNA sequencing data analysis. We additionally applied standardized Braak staging to investigate whether AD progression correlates with alterations in MCT8 expression. We demonstrate robust MCT8 expression across brain barriers, glial cells, and in distinct neuronal populations. RNAscope confirmed a strong concordance between SLC16A2 mRNA presence and MCT8 immunoreactivity. STED and confocal microscopy localized MCT8 to plasma membranes, perinuclear regions, and axonal/dendritic compartments, indicating roles in both trans- and intracellular TH transport. MCT8 expression was preserved across Braak stages, with no significant difference between donors with varying degrees of neurofibrillary pathology. Our findings establish a comprehensive cellular and regional framework for MCT8-mediated transport in the human brain, mapping its specific anatomical distribution across regions crucial for motor control and cognitive processing. Stable MCT8 expression across Braak stages suggests that cerebral TH dysregulation in AD likely reflects altered hormone metabolism rather than transporter loss.},
}

Humans
*Monocarboxylic Acid Transporters/metabolism/genetics
Symporters
Aged
*Brain/metabolism/pathology
Female
Male
Adult
Middle Aged
*Aging/metabolism/pathology
*Thyroid Hormones/metabolism
Aged, 80 and over

@article {pmid42823800,
year = {2026},
author = {Kharitonova, EV and Chen, B and Sun, Q and Ockerman, F and Chen, C and Zhou, LY and Tian, S and Cao, H and Ober, C and Cox, NJ and Tao, R and Li, Y},
title = {EndoPRS-SS: Summary-statistic based incorporation of endophenotypes to improve risk prediction.},
journal = {HGG advances},
volume = {},
number = {},
pages = {100677},
doi = {10.1016/j.xhgg.2026.100677},
pmid = {42823800},
issn = {2666-2477},
abstract = {Endophenotypes are critical biological markers with genetic links to disease progression. We previously developed endoPRS, a multi-trait polygenic risk score (PRS) method that leverages endophenotype data to improve disease risk prediction. However, endoPRS requires individual-level genotype-phenotype data for model fitting, restricting its broader use. To address this, we introduce endoPRS-SS, an extension which enables PRS inference using genome-wide association study (GWAS) summary statistics and LD reference panels. Through simulation and real data analysis, we demonstrate that endoPRS-SS maintains the predictive accuracy of endoPRS, while increasing computational efficiency up to 90-fold. We also extend the endoPRS framework to support the incorporation of multiple endophenotypes simultaneously and find that multi-endophenotype PRS outperform single-endophenotype PRS. Notably, incorporating both monocyte count and executive function scores significantly improves Alzheimer's disease prediction for Europeans in the UK Biobank cohort. These extensions expand the scope of endoPRS and strengthen its utility for large-scale genetic risk assessment.},
}

@article {pmid42823958,
year = {2026},
author = {Lanata, S and Windon, C and Tee, BL and de Leon, J and Aguirre, GA and Jackson, AJ and Lieu, K and Diaz, V and Escudero, SP and Hill-Jarrett, TG and Weng, A and Adewale, K and Amiuri, A and Archila, J and Calderon, LM and Chen, A and Chen, Y and Ching, A and Colverson, A and Lopera, CC and Dorsman, K and Fuentes-Juarez, B and Garcia, A and Guevarra, A and Joo, YM and Kaczmarska, M and Erismas, KR and Klein, J and Kornhuber, A and Lay, S and Leng, F and Light, SW and Li, K and Lopez, L and Macri, D and Mamuyac, E and Martinez Roman, L and Mei, D and Caipa, MP and Prioleau, C and Dionisio Reyes, RJ and Robles-Archila, O and Rodriguez, D and Shibiru, I and Suntay, JM and Thomas, K and Tucker, M and Wang, YT and Wu, J and Zhao, X and Smith, K and Gorno-Tempini, ML and Seeley, WW and Rosen, HJ and Valcour, V and Kramer, JH and Possin, K and Rabinovici, G and Miller, BL},
title = {From neighborhoods to brain health: an outreach model linking health literacy, cognitive care, research, and the arts, in San Francisco.},
journal = {Frontiers in public health},
volume = {14},
number = {},
pages = {1930344},
pmid = {42823958},
issn = {2296-2565},
mesh = {Humans ; San Francisco ; *Health Literacy ; *Community-Institutional Relations ; *Residence Characteristics ; Aged ; *Brain ; Cognition ; Aging ; },
abstract = {Traditional community outreach, research recruitment, and engagement strategies in aging neuroscience often fail to target and capture the diversity of structural and environmental conditions that shape the risk of age-related neurocognitive disorders (NCDs), including Alzheimer's disease. In this manuscript, we describe the rationale, implementation, and outcomes of the Community Outreach Program (COP) of the UCSF Fein Memory and Aging Center (MAC), emphasizing its neighborhood-based initiative designed to engage vulnerable populations to improve brain health literacy, access to cognitive care, and research inclusion among older adults living in underserved San Francisco neighborhoods. Guided by a social and environmental determinants of brain health framework, the program used neighborhood-level vulnerability and research representation mapping to identify neighborhoods with high vulnerability and low engagement in research, then implemented a multilingual, community-engaged model centered on four pillars: brain health education, arts- and movement-based programming, community-based cognitive clinics, and multilingual media outreach. Delivered in partnership with community organizations and safety-net providers in Mandarin, Cantonese, Spanish, Tagalog, and English, this model has generated durable partnerships across vulnerable neighborhoods, expanded access to culturally responsive cognitive care, improved inclusion in brain aging and NCDs research, and fostered innovative research projects. From 2019 to 2025, representation of individuals from vulnerable and underrepresented San Francisco neighborhoods in UCSF Fein MAC observational research increased substantially compared to previous years. These findings support place-based, multilingual, and reciprocity-centered community engagement as a promising framework for reducing and studying disparities in brain health.},
}

Humans
San Francisco
*Health Literacy
*Community-Institutional Relations
*Residence Characteristics
Aged
*Brain
Cognition
Aging

@article {pmid42824080,
year = {2026},
author = {Privšek, E and Marseglia, A and Košutić, I and Rosenberg, A and Granberg, T and Kramberger, MG and Kivipelto, M and Westman, E},
title = {Cerebral microbleed assessment on MRI in a memory clinic: Reliability, prevalence, and implications for anti-amyloid therapy.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {4},
pages = {e70472},
pmid = {42824080},
issn = {2352-8729},
abstract = {INTRODUCTION: Cerebral microbleeds (CMBs) represent an important magnetic resonance imaging (MRI) marker of cerebral small vessel pathology in memory-clinic populations, where vascular and neurodegenerative pathologies frequently overlap.

METHODS: This cross-sectional study included 747 patients from a Swedish memory clinic who underwent 3T MRI with susceptibility-weighted imaging. Two readers assessed CMBs using standardized criteria. Inter- and intra-observer agreement were evaluated before and after protocol refinement. CMB prevalence and burden were analyzed across diagnostic groups and by cerebrospinal fluid amyloid status.

RESULTS: CMBs were present in 28.6% of patients and frequently observed in subjects with mild cognitive impairment or dementia. Inter-observer agreement improved from κ = 0.71 to κ = 0.82 after protocol refinement. Among amyloid-positive patients with cognitive impairment, 11.2% exceeded proposed CMB thresholds for anti-amyloid therapy eligibility.

DISCUSSION: Standardized CMB assessment improves reliability in memory-clinic populations. Given its growing impact on treatment eligibility and safety, consistent evaluation is essential for patient management.},
}

@article {pmid42824090,
year = {2026},
author = {Schwartz, NU and Ellingson, T and Nguyen, H and Lin, Z and Ashton, NJ and Dage, JL and Deniz, K and Dietz, CD and Ljubenkov, PA and Miller, BL and Nael, K and Possin, K and Rojas, JC and Rosen, HJ and Saloner, R and Soleimani-Meigooni, DN and Staffaroni, AM and Stephens, ML and Tammewar, G and Wang, Y and La Joie, R and Rabinovici, GD and Boxer, AL and VandeVrede, L},
title = {Evaluation of plasma neurofilament and glial fibrillary acidic protein to predict or detect amyloid related imaging abnormalities.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {4},
pages = {e70446},
pmid = {42824090},
issn = {2352-8729},
abstract = {INTRODUCTION: Amyloid-targeting therapies (ATT) require frequent magnetic resonance imaging monitoring to detect vasogenic edema and hemorrhage, i.e., amyloid-related imaging abnormalities (ARIA). Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are potential blood-based biomarkers (BBM) of ARIA.

METHODS: Plasma NfL and GFAP were longitudinally collected in an ATT clinic and natural log transformed. Baseline, pre-ARIA, and trajectories were compared between patients with (N = 15) and without (N = 45) ARIA.

RESULTS: Baseline NfL and GFAP did not differ between patients with or without ARIA (ln[NfL] ECLIA 1.24 ± 0.38 pg/mL vs 1.25 ± 0.40 pg/mL, p = 0.77; ln[NfL] Simoa 2.87 ± 0.47 pg/mL vs 2.98 ± 0.40 pg/mL, p = 0.30, ln[GFAP] ECLIA 4.95 ± 0.36 pg/mL vs 4.88 ± 0.47 pg/mL, p = 0.69). No significant changes were seen at the timepoint preceding ARIA, and ARIA incidence made no detectable impact on biomarker trajectories.

DISCUSSION: Biobanking in treatment clinics can evaluate clinical utility of BBMs as monitoring tools. These findings do not support a strong association between NfL or GFAP and ARIA in the ATT clinic.},
}

@article {pmid42824337,
year = {2026},
author = {Beltrán, ÓG and Angarita-Rodríguez, A and González, J and Hernández, ED and Pinzón, A},
title = {Gut microbiota signatures in mild cognitive impairment: a scoping review of microbial taxa and clinical implications.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1895237},
pmid = {42824337},
issn = {1664-302X},
abstract = {OBJECTIVE: To identify systematically the typical gut microbiota in mild cognitive impairment patients and its association in disease progression. Systematically identify microbial taxa consistently associated with Mild Cognitive Impairment.

DESIGN: A scoping review was performed according to the guidelines of the Joanna Briggs Institute using CoCoPop design.

STUDY SELECTION: Several studies about gut microbiota sequencing in mild cognitive impairment diagnosed patients compared against healthy controls.

METHODS: Searches in PubMed, Embase, Scopus, and Web of Science using MeSH and DeCS terms, were performed up to December 2025. Two reviewers independently screened titles and abstracts. Then, the full texts were reviewed to select documents to be included. When there were disagreements in papers selection, those were resolved after discussions among the reviewers. Relevant data information from selected publications was extracted, and a descriptive analysis was made.

RESULTS: The documents do not show drastic changes in the alpha or beta diversity of the microbiota, but they do identify consistent alterations in the relative abundance of specific taxa that allow patients with MCI to be distinguished from healthy controls. Among the most relevant findings is the decrease in SCFA-producing genera, such as Ruminococcus and Lachnospira, whose reduction is directly associated with the deterioration of key brain functions, including synaptic processes and neuronal oxidative metabolism. On the other hand, there is an increase in proinflammatory taxa such as Bacteroides, a pattern that is similar to that observed in patients with Alzheimer's disease, although generally less pronounced.

CONCLUSION: The results highlight that alterations in the abundance of specific bacteria, characterized by the loss of protective taxa and an increase in proinflammatory bacteria, serve as early biomarkers for detecting and predicting Mild Cognitive Impairment (MCI). This pattern of proinflammatory dysbiosis can be identified even in preclinical stages, and it has been proposed as a potential noninvasive tool for early diagnosis and therapeutic intervention before dementia progresses.},
}

@article {pmid42824359,
year = {2026},
author = {Aversi, MTM and Freitas, PM and Aversi-Ferreira, TA},
title = {New Alzheimer's disease diagnostics and psychological clinical perspectives.},
journal = {Frontiers in psychology},
volume = {17},
number = {},
pages = {1866853},
pmid = {42824359},
issn = {1664-1078},
abstract = {Recent advances in blood-based biomarkers have transformed the early diagnosis of Alzheimer's disease (AD), enabling the identification of biological risk at preclinical and presymptomatic stages in a noninvasive and accessible manner. Despite this diagnostic progress, the expansion of psychological clinical services in dementia care has not kept pace, representing a critical gap in the current management of AD. This theoretical paper critically discusses the role of psychological clinical practice in the prevention and management of AD in light of these diagnostic advances, particularly from the perspective of the International Working Group (IWG), which defines AD as a clinical-biological entity and recommends that cognitively normal individuals with positive biomarkers be considered at risk rather than diagnosed. Based on this framework and on evidence from the 2024 Lancet Commission on dementia prevention, we propose a three-phase roadmap for the integration of psychological care into multidisciplinary AD management. Phase 1 encompasses universal prevention through psychoeducation, cognitive reserve promotion, and emotional education. Phase 2 targets at-risk individuals with elevated biomarker profiles, focusing on neuropsychological evaluation, risk disclosure support, and early cognitive intervention. Phase 3 addresses individuals with established AD through cognitive rehabilitation and caregiver support. We further argue that government policies must integrate psychologists into multidisciplinary neurological and geriatric teams, and that psychology training programs must be updated to prepare professionals for preventive roles. More research on standardized psychological protocols for pre-dementia contexts is urgently needed.},
}

@article {pmid42824632,
year = {2026},
author = {Miao, J and Xue, C and Yan, X and Gu, J and Chu, D and Sun, H},
title = {From seeds to symptoms: the molecular landscape of tau seeding in Alzheimer's disease.},
journal = {Frontiers in neuroscience},
volume = {20},
number = {},
pages = {1927017},
pmid = {42824632},
issn = {1662-4548},
abstract = {Alzheimer's disease (AD) is the leading cause of dementia in the elderly, pathologically defined by extracellular amyloid-β plaques and intracellular neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau. The Braak staging system established that tau pathology spreads in a stereotypical pattern across the brain, supporting the "prion-like" hypothesis: misfolded tau aggregates serve as seeds, inducing the misfolding and aggregation of normal tau, and thereby driving disease progression along neuroanatomical pathways. In the past 5 years (2021-2026), substantial advances have elucidated the molecular mechanisms underlying tau seeding activity. This review summarizes recent progress in tau seeding research, highlighting both intrinsic and extrinsic regulators of tau prion-like activity. Intrinsic factors include the structural basis of tau strains, MAPT mutations, alternative splicing (3R/4R isoforms), post-translational modifications, and liquid-liquid phase separation. Extrinsic factors encompass cofactors, molecular chaperones, non-coding RNAs, epigenetic mechanisms, environmental exposures, and the emerging concept of trans-seeding by heterologous protein fibrils. We also review therapeutic strategies targeting tau pathology, focusing on their mechanisms and clinical development. Integrating these mechanistic insights and therapeutic advances will inform future research and clinical strategies for AD and related tauopathies.},
}

@article {pmid42824777,
year = {2026},
author = {Taherkhani, AM and Şenol, H and Valizadeh, Y and Ghafouri, SN and Dastyafteh, N and Aktaş, A and Sadeghian, N and Moradkhani, F and Larijani, B and Biglar, M and Taslimi, P and Mohammadi-Khanaposhtani, M and Mahdavi, M},
title = {Design and synthesis of carbazole-acrylamide-pyridinium hybrids as dual acetylcholinesterase/butyrylcholinesterase inhibitors and evaluation of their cytotoxic profile on SH-SY5Y and HEK293 cell lines.},
journal = {RSC medicinal chemistry},
volume = {},
number = {},
pages = {},
pmid = {42824777},
issn = {2632-8682},
abstract = {A novel series of seventeen carbazole-acrylamide-pyridinium-N-phenylacetamide hybrids (12a-q) was designed and synthesized as dual inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) for potential Alzheimer's disease therapy. Their inhibitory activity was evaluated against both enzymes using tacrine and galantamine as reference standards. Tacrine exhibited IC50 values of 58.34 nM against AChE and 160.50 nM against BChE, while galantamine showed 124.72 nM and 216.23 nM, respectively. The synthesized derivatives demonstrated IC50 values ranging from 6.41 to 74.93 nM against AChE and from 38.05 to 191.96 nM against BChE. All compounds were more potent than galantamine, and most outperformed tacrine as well. Compound 12i was the most potent AChE inhibitor (IC50 = 6.41 nM), showing 9.1-fold and 19.5-fold higher potency than tacrine and galantamine, respectively. Compound 12g was the strongest BChE inhibitor (IC50 = 38.05 nM), with 4.2-fold and 5.7-fold higher activity than tacrine and galantamine. Kinetic analysis revealed that all of the most potent compounds act as competitive inhibitors. Cytotoxicity evaluation revealed that compounds 12i and 12g exhibited lower toxicity toward HEK293 cells than sorafenib, with favorable selectivity toward SH-SY5Y cells. These results establish the carbazole-acrylamide-pyridinium scaffold as a promising lead for developing safer cholinesterase inhibitors for Alzheimer's disease.},
}

@article {pmid42824999,
year = {2026},
author = {Bai, Y and Zhao, J and Zhang, S and Yan, C and Chen, Y and Du, G and Liu, A},
title = {Machine Learning-Guided Discovery of Natural BACE1 Inhibitors with Enzymatic and Cellular Validation.},
journal = {ACS omega},
volume = {11},
number = {38},
pages = {58100-58111},
pmid = {42824999},
issn = {2470-1343},
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by excessive accumulation of β-amyloid (Aβ) peptides in the brain. Beta-secretase 1 (BACE1), the rate-limiting enzyme in the amyloidogenic processing pathway of amyloid precursor protein (APP), has been widely recognized as an important therapeutic target for reducing Aβ production. In the present study, nine machine learning-based predictive models for BACE1 inhibitors were constructed using Naïve Bayes (NB) and Recursive Partitioning (RP) algorithms. Subsequently, internal and external validations were conducted to evaluate predictive performance. The optimized models were subsequently applied to screen an in-house natural product library containing 452 compounds. Based on consensus prediction criteria, 171 compounds were identified as potential BACE1 inhibitors and subjected to fluorescence resonance energy transfer (FRET)-based enzymatic assays. Among them, 33 compounds exhibited inhibitory rates greater than 50% at an initial concentration of 50 μg/mL. Further dose-response evaluation identified five compounds with IC50 values below 50 μM, including Theaflavin-3,3'-digallate, γ-mangostin, Licoagrochalcone B, Chicoric acid, and Resveratrol. Cell-based validation using APPswe-HEK293T cells demonstrated that Theaflavin-3,3'-digallate significantly reduced extracellular Aβ1-42 secretion. Molecular docking analysis further revealed that Theaflavin-3,3'-digallate could stably bind to BACE1 through multiple hydrogen-bond and hydrophobic interactions. Collectively, this study demonstrates that integrating machine learning-assisted virtual screening with natural product libraries is an effective strategy for discovering novel BACE1 inhibitors. Theaflavin-3,3'-digallate was identified as a promising natural BACE1 inhibitor with both enzymatic and cellular activities. This research provides new technology and potential lead compound for the development of future anti-Alzheimer's disease drug.},
}

@article {pmid42825043,
year = {2026},
author = {Wu, M and Cao, Y and Wu, X and Wang, Y and Deng, Z and Zhao, Y and Lu, G and Qu, X and Zhu, F and Cheng, Y and Wang, P and Zhong, L},
title = {Comprehensive metabolite profiling in fruits of different Prunus cultivars.},
journal = {Food chemistry: X},
volume = {39},
number = {},
pages = {104431},
pmid = {42825043},
issn = {2590-1575},
abstract = {Variations in metabolite profiles among Prunus cultivars shape fruit flavor and overall quality, and ultimately determine consumer preference. To comprehensively evaluate the metabolic quality of various Prunus cultivars, we adopted an integrated extraction strategy to obtain distinct metabolite fractions from identical samples. In this work, seven predominant Prunus cultivars from Xinjiang, China were investigated, 382 volatile metabolites and 417 non-volatile metabolites were identified, where phenols were detected as the dominant secondary metabolites and esters were abundant volatile metabolites. 'Black' displayed greater antioxidant activity relative to other cultivars, due to its more than four-fold higher content of pyroglutamic acid, glutamine, and γ-dodecalactone. Additionally, network pharmacology analysis confirmed that the metabolites maybe associated with diabetes, cancer, and Alzheimer's disease. Collectively, this study for the first time elucidates the full metabolite profile in Prunus, and provides practical guidance for consumer choices as well as a solid theoretical foundation for selective breeding of Prunus.},
}

@article {pmid42825245,
year = {2026},
author = {Jia, M and Yang, R and Xu, Y and Wu, Z and Lu, J and Li, Z and Yan, Q and Fan, G and Gui, Y},
title = {Oral microbiome-metabolome axis links glycerophospholipid dysregulation to Alzheimer's disease.},
journal = {Journal of oral microbiology},
volume = {18},
number = {1},
pages = {2732297},
pmid = {42825245},
issn = {2000-2297},
abstract = {INTRODUCTION: This study aimed to evaluate the feasibility of using tongue biofilm as a non-invasive, patient-friendly, and cost-effective biomarker source for identifying early microbial and metabolic disturbances associated with Alzheimer's disease (AD).

MATERIALS AND METHODS: A total of 62 outpatients were enrolled (31 with AD and 31 cognitively normal controls). Tongue biofilm samples were analyzed using 16S rRNA sequencing and untargeted metabolomics via UPLC-Q/TOF-MS. Additionally, cerebrospinal fluid (CSF) samples from 36 individuals (18 per group) were examined under identical untargeted metabolomics processing protocols to validate the metabolomic findings.

RESULTS AND DISCUSSION: Microbiome analysis revealed an increased relative abundance of Proteobacteria in the AD group, while Firmicutes and Bacteroidetes were enriched in controls. Metabolomic profiling identified 88 significantly different metabolites between groups, 64 of which achieved area under the curve (AUC) values > 0.90 in the ROC analysis. Glycerophospholipid metabolism has emerged as a key dysregulated pathway in AD, a finding further corroborated by CSF metabolomic analysis. Tongue biofilm represents a non-invasive, cost-effective, and accessible biomarker source, offering potential for AD diagnosis and research when coupled with microbiome and metabolomic analyses. Moreover, the role of glycerophospholipid metabolism in AD pathogenesis warrants further investigation.},
}

@article {pmid42825350,
year = {2026},
author = {Chen, J and Long, Z and Li, Y and Luo, M and Luo, S and He, G},
title = {[Corrigendum] Alteration of the Wnt/GSK3β/β‑catenin signalling pathway by rapamycin ameliorates pathology in an Alzheimer's disease model.},
journal = {International journal of molecular medicine},
volume = {58},
number = {5},
pages = {},
doi = {10.3892/ijmm.2026.6003},
pmid = {42825350},
issn = {1791-244X},
abstract = {Following the publication of the above article, a concerned author drew to the authors' attention that they had apparently used an inappropriate antibody in their study: In the Materials and methods section, the authors had reported the use of Abcam's recombinant antibody against plant homeodomain (PHD) finger protein 1 (a.k.a. PHF1; cat. no. ab184951) to probe for the unrelated protein, tau paired helical filaments (PHFs). Based on their search of previous literature, the authors acknowledged that they had made a methodological error in selecting the incorrect antibody; therefore, the western blot assay results shown in Fig. 4A on p. 317 for protein PHF1 should be considered to be invalid. Given that this issue has come to light, the authors have now purchased the correct and specific antibody targeting phosphorylated tau (p‑tau‑S404) from ABclonal Viotech Co., Ltd (cat. no. AP1378) and completely repeated the relevant experiments, in strict accordance with the original experimental protocols and conditions. In addition, the authors provided the Editorial Office with the raw data from the repeated experiments, and also proof of purchase of the correct antibody. The corrected version of Fig. 4, now showing the revised data for the PHF1 blots in Fig. 4A together with re‑quantified bar charts for these data shown in Fig. 4B, is featured on the next page. Additional changes to the text should also be noted: The text in the Materials and methods section, 'Western blot analysis' subsection, on p. 315 (left-hand column, lines 14-15), should read as follows (changes highlighted in bold): '...rabbit anti insulin degrading enzyme (IDE) antibody (ab133561), rabbit anti‑PHF‑1 antibody (ab184951), mouse anti‑GSK3β antibody (ab93926)...'. In addition, revisions have also been made to the legend for Fig. 4. The authors confirm that the error made in performing these experiments has not had a significant impact on either the results or the conclusions reported in this study, and all the authors agree with the publication of this Corrigendum. The authors are grateful to the Editor of International Journal of Molecular Medicine for allowing them the opportunity to publish this Corrigendum; furthermore, they apologize to the readership of the Journal for any inconvenience caused. [International Journal of Molecular Medicine 44: 313‑323, 2019; DOI: 10.3892/ijmm.2019.4198].},
}

@article {pmid42813639,
year = {2026},
author = {Singh, AP and Prajapati, S and Yadav, S and Yadav, A},
title = {Lipid-based Nanocarriers for Neurodegenerative Disorders: Bridging Blood-brain Barrier Biology and Translational Drug Delivery.},
journal = {Current neurovascular research},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115672026478560260909100922},
pmid = {42813639},
issn = {1875-5739},
abstract = {INTRODUCTION: Neurodegenerative disorders, including Alzheimer's, Parkinson's, Huntington's disease, and amyotrophic lateral sclerosis, remain difficult to treat because the Blood-brain Barrier (BBB) severely restricts therapeutic access to the central nervous system. This review evaluates BBB biology and the potential of lipid-based nanocarriers to improve brain-targeted drug delivery and facilitate clinical translation.

METHODS: A structured narrative review of peer-reviewed preclinical and clinical literature published between 2000 and 2025 was conducted using PubMed, Scopus, and Web of Science. Evidence concerning BBB structure and transport mechanisms, lipid-based nanocarrier design, physicochemical characteristics, drug-release behavior, computational modelling, therapeutic applications, and translational challenges was critically synthesized.

RESULTS: Liposomes, nanoemulsions, solid lipid nanoparticles, nanostructured lipid carriers, and lipid-polymer hybrid nanoparticles demonstrated improved drug solubility, stability, controlled release, systemic circulation, and brain targeting. Preclinical evidence indicates enhanced brain bioavailability and therapeutic effects, including reductions in neuroinflammation, oxidative stress, and disease-associated pathological processes. However, clinical translation remains constrained by formulation complexity, scalability, long-term safety, and inconsistent clinical outcomes.

DISCUSSION: Integration of BBB transport biology with surface functionalization, receptormediated targeting, formulation engineering, and computational modelling may enable more rational nanocarrier development. Nevertheless, standardized characterization, reproducible manufacturing, comprehensive safety evaluation, and stronger clinical validation are required to bridge the gap between promising preclinical findings and therapeutic implementation.

CONCLUSION: Lipid-based nanocarriers represent promising platforms for overcoming biological and pharmacokinetic barriers in neurodegenerative disorders. Further optimization and rigorous translational validation are essential to establish their safety, reproducibility, and clinical effectiveness.},
}

@article {pmid42813641,
year = {2026},
author = {Küpeli, E and Mancak, M and Cakirli, E and Bardakci, H and Avci, TB and Ozdemir, S},
title = {Solid and Nanostructured Lipid Carriers for Plant-Derived Neuroprotective Agents: Advances and Future Perspectives.},
journal = {Current pharmaceutical design},
volume = {},
number = {},
pages = {},
doi = {10.2174/0113816128509583260914134550},
pmid = {42813641},
issn = {1873-4286},
abstract = {Neurodegenerative disorders, particularly Alzheimer's disease (AD) and Parkinson's disease (PD), continue to pose a substantial therapeutic challenge, largely due to progressive neuronal degeneration and the limited effectiveness of currently available treatments. Plant-derived bioactive compounds-including polyphenols, alkaloids, terpenoids, and flavonoids-have shown notable neuroprotective properties. However, their clinical use remains constrained by low bioavailability and limited ability to cross the blood-brain barrier (BBB). Lipid-based nanocarrier systems, especially solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), have emerged as promising alternatives for improving delivery efficiency. This review evaluates recent advances in SLN and NLC formulations developed for phytochemical delivery in neurodegenerative conditions, focusing on formulation approaches, production methods, and the physicochemical factors that govern system performance. Preclinical findings consistently indicate enhanced solubility, improved stability, and more effective brain targeting with these systems. Even so, several challenges continue to impede their clinical translation. In particular, issues related to formulation reproducibility, scalability of production, and long-term safety remain unresolved. Alternative administration routes such as intranasal delivery offer a potential strategy to bypass the BBB, although their practical feasibility still requires further confirmation. SLN- and NLC-based systems offer a promising approach, although their clinical development is still ongoing. Future efforts should focus on establishing standardized formulation protocols, conducting rigorous in vivo studies, and ensuring alignment with regulatory requirements to facilitate successful clinical translation.},
}

@article {pmid42813688,
year = {2026},
author = {Yu, H and Chang, W and Mahmut, D and Huang, C and Zhang, B},
title = {Integrative transcriptomic and regulatory network analysis reveals associations of seven proposed risk genes with immune-related molecular features in Alzheimer's disease.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261493169},
doi = {10.1177/13872877261493169},
pmid = {42813688},
issn = {1875-8908},
abstract = {BackgroundAlzheimer's disease (AD) involves neuroinflammation influenced by genetic and immune dysregulation. Seven proposed AD risk genes (CACNA2D3, EPB41L2, INPP5D, MYO1F, RBM47, SSH2, TBXAS1) have been identified, but their associations with the immune microenvironment (IME) remain unclear.ObjectiveThis study investigates associations between these genes and the neuroimmune landscape in AD.MethodsIntegrative transcriptomic and regulatory network analysis was performed using the GSE53697 dataset (9 AD and 8 control samples) from the GEO. Immune cell enrichment scores and pathway activity were evaluated using single-sample Gene Set Enrichment Analysis (ssGSEA), and enriched pathways were identified through Gene Set Enrichment Analysis (GSEA). Upstream regulatory associations were explored by constructing miRNA-mRNA and transcription factor regulatory networks, and correlations between the risk genes and established AD-related genes were assessed using public databases.ResultsAD samples showed immune dysregulation, including reduced dendritic cell ssGSEA scores. All seven risk genes correlated with immune cell subsets and immunomodulatory molecules. Enrichment analysis revealed inflammatory pathways including NF-κB, IL-17, TNF, MAPK, and Notch, suggesting potential links to neuroinflammation and neuronal signaling disruption. Upstream analysis identified 85 miRNAs and several transcription factor motifs annotated to HOXA13, ESRRA, and SNAI1/2/3. Correlation analysis further revealed associations between risk genes and AD-related genes, placing these genes within established AD pathological networks in an exploratory manner.ConclusionsThis exploratory study provides insights into how AD risk genes are associated with the IME and may be linked to neuroinflammatory pathways and neuronal function, providing hypotheses for future studies of immune-genetic crosstalk in AD pathogenesis.},
}

@article {pmid42813805,
year = {2026},
author = {Feng, J and Nanshan, M and Shi, H and Wong, KY and Lam, KF and Cao, J},
title = {A regularized semiparametric cure-rate model with high-dimensional imaging data.},
journal = {Statistical methods in medical research},
volume = {},
number = {},
pages = {9622802261483498},
doi = {10.1177/09622802261483498},
pmid = {42813805},
issn = {1477-0334},
abstract = {Structural magnetic resonance imaging (MRI) is informative for studying progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD), but incorporating high-dimensional images into survival models requires methods that accommodate irregular brain domains and yield interpretable spatial effects. We propose a regularized semiparametric mixture cure-rate model for high-dimensional imaging predictors that separates susceptibility to AD conversion from time to AD among susceptible subjects. Baseline MRI images are represented by bivariate Bernstein spline basis functions over a triangulation of the brain domain, and sparsity-inducing penalties are imposed on imaging effects in both incidence and latency components. This construction enables direct estimation of localized coefficient functions describing how image regions are associated with susceptibility and conversion time. We develop an expectation-maximization algorithm that updates latent susceptibility probabilities and solves penalized logistic and Cox regression subproblems, together with an efficient tuning strategy. Simulations show that the method can recover localized active regions and provide useful incidence and latency discrimination. An application to Alzheimer's Disease Neuroimaging Initiative data demonstrates susceptibility discrimination and interpretable brain-region coefficient maps.},
}

@article {pmid42814409,
year = {2026},
author = {Huang, S and Zhang, Z and Xia, J and Deng, M and Chen, F and Wang, M and Fei, Y and Jiang, Z and Lu, C and Fu, J and Guo, J and Zhou, H},
title = {ZBP1-mediated Treg cell dysfunction exacerbates neuroimmune dysregulation in Alzheimer's disease under metabolic stress.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {10},
pages = {e71896},
pmid = {42814409},
issn = {1552-5279},
support = {81871098//the National Science Foundation of China/ ; 81671392//the National Science Foundation of China/ ; 2021YFE0111800//National Key R&D Program of China/ ; ZY [2021-2023]-0207-01//National Key R&D Program of China/ ; shslczdzk02802//National Key R&D Program of China/ ; 2018SHZDZX01//National Key R&D Program of China/ ; },
mesh = {Animals ; *Alzheimer Disease/immunology/metabolism ; *T-Lymphocytes, Regulatory/immunology/metabolism ; Mice ; *Stress, Physiological/immunology ; *DNA-Binding Proteins/metabolism ; Humans ; *Neuroimmunomodulation ; Male ; Mice, Transgenic ; Disease Models, Animal ; Diet, High-Fat ; Brain/metabolism ; Female ; *RNA-Binding Proteins/metabolism ; },
abstract = {INTRODUCTION: Metabolic stress increases Alzheimer's disease (AD) risk, but mechanisms linking metabolic dysfunction to neuroimmune dysregulation remain unclear.

METHODS: We assessed cognition in community-dwelling participants and used high-fat diet (HFD)-fed 5xFAD mice, high glucose and high palmitate (HGHP)-treated regulatory T cell (Treg) co-cultures, and adoptive Treg transfer to evaluate metabolic stress-associated neuroimmune dysfunction. Flow cytometry, RNA sequencing, positron emission tomography computed tomography, and electrophysiology assessed Treg function, AD pathology, cerebral metabolism, and synaptic plasticity.

RESULTS: Metabolic stress impaired Treg stability and function, accompanied by increased Z-DNA-binding protein 1 (ZBP1) expression and activation of apoptotic and necroptotic signaling. Treg dysfunction was associated with enhanced glial activation and neuronal injury. Under HGHP stress, ZBP1-deficient Tregs showed improved survival and stronger immunosuppressive activity, more effectively limiting glial activation and preserving neuronal integrity. In vivo, ZBP1-deficient Treg transfer conferred greater neuroprotection than wild-type Treg transfer in HFD-fed AD mice.

DISCUSSION: ZBP1 may contribute to metabolic stress-induced Treg dysfunction and represent a candidate target to improve Treg-based therapy in HFD-fed AD mice.},
}

Animals
*Alzheimer Disease/immunology/metabolism
*T-Lymphocytes, Regulatory/immunology/metabolism
Mice
*Stress, Physiological/immunology
*DNA-Binding Proteins/metabolism
Humans
*Neuroimmunomodulation
Male
Mice, Transgenic
Disease Models, Animal
Diet, High-Fat
Brain/metabolism
Female
*RNA-Binding Proteins/metabolism

@article {pmid42814513,
year = {2026},
author = {Jia, H and Wu, S and Xue, X and Li, Z and Li, L and He, H and Wang, Q and Gao, H and Wen, C},
title = {A review on diffusion tensor imaging-based comprehensive intelligent diagnosis of Alzheimer's disease.},
journal = {Reviews in the neurosciences},
volume = {},
number = {},
pages = {},
pmid = {42814513},
issn = {2191-0200},
abstract = {AI-assisted early diagnosis of Alzheimer's disease (AD) has substantial clinical value, and diffusion tensor imaging (DTI), which captures white matter microstructural alterations, has considerable potential across the AD continuum. However, major barriers to clinical translation remain. This review systematically evaluated the evolution of algorithmic paradigms, the effectiveness of multimodal fusion, and barriers to clinical generalization in DTI-based AD diagnosis. Using an "Input-Model-Fusion" evaluation framework, we analyzed 98 studies published from 2010 to 2026 and compared sample size, diagnostic task, validation design, and methodological quality. Four findings emerged. 1) Modality selection should be task-driven; single-modality DTI and multimodal fusion have different applicability across diagnostic tasks. 2) Algorithm choice was closely related to sample size: conventional machine learning, particularly support vector machines, predominated in small-sample studies, whereas deep learning architectures, including convolutional neural networks, graph convolutional networks, and Transformers, were more widely used with large datasets. 3) Substantial performance degradation in multicenter or external validation highlighted persistent limitations in clinical generalizability. Data source, sample representativeness, feature processing, validation strategy, acquisition protocol, and software pipeline heterogeneity remain important constraints on clinical translation and cross-study comparability of DTI metrics. 4) Hippocampal pathways, the corpus callosum, fornix, and cingulum showed relatively stable discriminative value. Future research should move beyond "algorithm accuracy competition" toward clinical pragmatism by prioritizing task alignment, standardized DTI acquisition and processing, external validation, and neurobiological interpretability.},
}

@article {pmid42814589,
year = {2026},
author = {Singh, L and Gupta, GD and Singh, S},
title = {Neurobehavioral and Molecular Rescue by Dapagliflozin in Aluminum Chloride-Induced Alzheimer's Model: Possible Relevance of NF-κB and Aβ(1-42).},
journal = {Assay and drug development technologies},
volume = {},
number = {},
pages = {1540658X261486541},
doi = {10.1177/1540658X261486541},
pmid = {42814589},
issn = {1557-8127},
abstract = {Alzheimer's disease (AD), a progressive neurodegenerative disorder, characterized by the deposition of amyloid-β plaques in the hippocampus, leading to cognitive and behavioral impairments. This study investigated the neuroprotective outcome of Dapagliflozin (DAPA), a sodium-glucose cotransporter 2 inhibitor primarily used for glycemic control, which also exhibits notable anti-inflammatory, antioxidant, and neuroprotective properties. Using an aluminum chloride (AlCl3)-induced rat model of AD, the research evaluates behavioral, biochemical, and neuroinflammatory changes, particularly focusing on the nuclear factor kappa-B protein (NF-κB) signaling pathway. Rats were orally administered AlCl3 to induce AD-like pathology, followed by DAPA treatment (1 and 2 mg/kg, p.o.) over a 28-day period. Behavioral assessments, including the Morris water maze and Elevated Plus Maze, were used to evaluate spatial memory and anxiety. On day 29, hippocampal tissues were collected to assess neurotransmitter levels, oxidative stress markers (LPO, GSH, nitrite), and inflammatory cytokines (interleukin-1 beta, interleukin-6), along with the expression of NF-κB. AlCl3 exposure led to significant alterations in neurotransmitter balance (AChE, GABA, and glutamate), heightened oxidative stress, and increased neuroinflammatory responses. DAPA treatment significantly mitigated these changes, notably downregulating NF-κB, which correlated with decreased amyloid beta and expression in the hippocampus. These findings suggest that beyond its antidiabetic action, DAPA offers promising neuroprotection against AlCl3-induced neurotoxicity, potentially via modulation of the NF-κB signaling pathway.},
}

@article {pmid42814649,
year = {2026},
author = {Liguori, C and Carpi, M},
title = {The orexinergic system in Alzheimer's disease: from sleep disruption to accelerated neurodegeneration.},
journal = {European neurology},
volume = {},
number = {},
pages = {1},
doi = {10.1159/ene/acsag009},
pmid = {42814649},
issn = {1421-9913},
abstract = {BACKGROUND: Sleep-wake dysregulation is increasingly recognized as an early and clinically relevant feature of Alzheimer's disease (AD), with growing evidence supporting a bidirectional relationship between disturbed sleep and AD pathophysiology. Sleep fragmentation, reduced slow-wave and REM sleep may contribute to amyloid-β (Aβ) accumulation by increasing Aβ production during wakefulness and diminishing glymphatic clearance during sleep, while emerging amyloid pathology can further disrupt sleep architecture and circadian sleep-wake rhythm, reinforcing a feed-forward cycle.

SUMMARY: Within this framework, the orexinergic system, centered in the hypothalamus and crucial for arousal and sleep-wake stability, has been implicated as a mechanistic link between hyperarousal, impaired sleep consolidation, and altered amyloid dynamics. Preclinical studies suggested that orexin-A signaling can exacerbate Aβ and tau pathology and impair synaptic function, whereas biomarker studies reported high cerebrospinal fluid orexin-A levels in mild cognitive impairment and dementia due to AD. These observations raise the hypothesis that targeting orexin signaling and improving sleep may represent actionable strategies within the AD continuum.

KEY MESSAGES: Clinical evidence indicates that behavioral and pharmacological interventions can improve sleep in at-risk populations, yet robust proof of disease-modifying effects on AD biomarkers or clinical progression remains limited. Ongoing trials of dual orexin receptor antagonists may clarify whether sustained modulation of sleep-wake regulation can influence AD-related biology beyond symptomatic sleep benefits.},
}