@article {pmid41856514,
year = {2026},
author = {Haddad-Santos, D and Moura, CB and Martinez, MT and Morgado, A and Callegaro, D and Kiderman, A and Anghinah, R},
title = {Portable eye-tracking in neurology: current uses and future perspectives in cognition.},
journal = {Arquivos de neuro-psiquiatria},
volume = {84},
number = {1},
pages = {1-10},
doi = {10.1055/s-0046-1817035},
pmid = {41856514},
issn = {1678-4227},
mesh = {Humans ; *Eye-Tracking Technology/instrumentation/trends ; Reproducibility of Results ; *Eye Movements/physiology ; *Cognition Disorders/diagnosis/physiopathology ; Neurology/instrumentation ; *Nervous System Diseases/physiopathology ; },
abstract = {Eye tracking technology has emerged as a pivotal tool in neurology, providing objective insights into ocular motor function and cognitive processes across various neurological conditions, including mild traumatic brain injury, autism spectrum disorder, schizophrenia, attention deficit hyperactivity disorder, and neurodegenerative diseases like Alzheimer's and Parkinson's disease.The present systematic review evaluates the current applications and reliability of portable eye-tracking devices in clinical practice, highlighting their transformative potential for diagnosing and monitoring cognitive disorders.A systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Observational studies using portable eye-tracking devices were included. Databases searched included PubMed, Embase, and Cochrane, with studies screened and reviewed by two independent authors. Outcomes assessed were eye movements and visual responses in neurological patients. The Critical Appraisal Skills Program (CASP) checklist was used to assess study quality and bias.A total of 62 studies were identified, with 27 included after screening. The findings reveal significant advancements in device accessibility, sampling rates, and accuracy, which enhance the ability to detect subtle cognitive changes through eye movement patterns. Portable devices such as Neurolign DX 100 (Neurolign USA, LLC) and Tobii (Tobii), which is a portable video-oculography (VOG) devices including Neurolign DX 100 and Tobii systems, were highlighted for their precision and applicability in clinical settings.Portable eye-tracking devices show promise for detecting cognitive impairments in neurological conditions like multiple sclerosis. Their portability and ease of use facilitate widespread clinical application, making cognitive assessments more accessible and effective in early diagnosis and monitoring of disease progression.},
}

Humans
*Eye-Tracking Technology/instrumentation/trends
Reproducibility of Results
*Eye Movements/physiology
*Cognition Disorders/diagnosis/physiopathology
Neurology/instrumentation
*Nervous System Diseases/physiopathology

@article {pmid41857195,
year = {2026},
author = {Wen-Xia, H and Zhong-Wen, H and Yu, M and Han, Z and Wei-Ze, L and Li, G and Ning, Z and Lin, W and Min, J and Shan-Shan, M},
title = {Co-cultivation Serratia marcescens with Trichoderma harzianum for improving production of Huperzine A.},
journal = {Applied microbiology and biotechnology},
volume = {110},
number = {1},
pages = {},
pmid = {41857195},
issn = {1432-0614},
support = {2019PT-26//the Science and Technology Innovation Base-Open and Sharing Platform of Science and Technology Resources Project of Shaanxi Province/ ; Shaanxi Education No. 30 [2022]//Biological breeding and green synthesis of endangered precious medicinal materials future Industrial Innovation Research Institute/ ; 2022NLTS103//Xi'an Medical University/ ; 24JC080//Shaanxi Provincial Department of Education service local exceptional/ ; 24KJCX062//State General Administration of Sport, based on multi-omics to explore the effects of aerobic exercise on the regulatory mechanism of organ and pancreas microenvironment/ ; },
mesh = {*Serratia marcescens/metabolism/growth & development/isolation & purification/genetics ; *Alkaloids/biosynthesis/metabolism ; *Sesquiterpenes/metabolism ; Huperzia/microbiology/metabolism ; Coculture Techniques ; RNA, Ribosomal, 16S/genetics ; Culture Media/chemistry ; *Hypocreales/metabolism/growth & development ; Endophytes/metabolism/isolation & purification ; },
abstract = {Plant-derived (-)-Huperzine A (HupA), the bioactive enantiomer of the acetylcholinesterase inhibitor used for Alzheimer's disease (AD) therapy, is limited by the scarcity of Huperzia serrata (HS), while chemically synthesized (+)-HupA is clinically unviable due to high toxicity and low activity (1/30 that of (-)-HupA), creating a critical bottleneck for HupA pharmaceutical development that necessitates microbial biosynthesis solutions. In this study, we isolated the endophytic bacterium Serratia marcescens HL-1 from HS (identified via morphological characterization and 16S rRNA sequencing) and developed a novel co-cultivation strategy with Trichoderma harzianum NSW-V in modified PDA medium (26 °C, 2 days): This co-cultivation system sustained the stable HupA biosynthetic capacity of both Serratia marcescens HL-1 and Trichoderma harzianum NSW-V, synergistically enhancing the (-)-HupA yield of the endophytic bacterium to 32.976 ± 0.21 mg/L (biosynthetic HupA, BHA) and concurrently boosting the HupA production of the fungal strain; this revealed a positive upward trend in HupA yield with co-cultivation intervention, but no statistically significant differences were observed between groups (p > 0.05), and notably co-cultivation restored the strain's HupA-synthesizing capacity when its native production potential declined. BHA exhibited physicochemical properties and crystal structure identical to plant-derived (-)-HupA (PHA), as validated by NMR spectroscopy and molecular docking analyses. Furthermore, we identified a novel pharmacological role for HupA: BHA protected pancreatic islet β-cells in a palmitic acid-induced injury model, where cell viability increased from 58.2% to 71.2% (one-way ANOVA followed by Dunnett's test, p < 0.01, n = 3 independent experiments), revealing an unprecedented role of HupA in pancreatic β-cell protection beyond its well-established anti-AD activity. KEY POINTS: • Co-cultivation of endophytic fungi and bacteria could highly express prior HupA.},
}

*Serratia marcescens/metabolism/growth & development/isolation & purification/genetics
*Alkaloids/biosynthesis/metabolism
*Sesquiterpenes/metabolism
Huperzia/microbiology/metabolism
Coculture Techniques
RNA, Ribosomal, 16S/genetics
Culture Media/chemistry
*Hypocreales/metabolism/growth & development
Endophytes/metabolism/isolation & purification

@article {pmid41857203,
year = {2026},
author = {},
title = {A biomarker of Alzheimer's disease could be a useful diagnostic tool for other amyloidoses.},
journal = {Nature medicine},
volume = {},
number = {},
pages = {},
pmid = {41857203},
issn = {1546-170X},
}

@article {pmid41857352,
year = {2026},
author = {Castellon-Lopez, Y and Aguilar-Hernandez, L and Guzman-Ruiz, IY and de Cordova, SF and Del Carmen Rosales, M and Salazar, JN and Pinzon, MM},
title = {Enhancing Participation in Alzheimer's Research: A Comparative Study of Community Health Worker -Led and Digital Recruitment Strategies in Hispanic/Latino Communities.},
journal = {Journal of racial and ethnic health disparities},
volume = {},
number = {},
pages = {},
pmid = {41857352},
issn = {2196-8837},
}

@article {pmid41857397,
year = {2026},
author = {Liu, J and Peng, F and Li, P and Yao, C and Jin, S and Wu, G and Zhang, T and Liang, Q and Wang, X and Du, X},
title = {Mechanistic insights into cannabidiol-mediated TrkB activation via FRS2 interaction in attenuating Alzheimer's disease pathology and cognitive impairment.},
journal = {Molecular psychiatry},
volume = {},
number = {},
pages = {},
pmid = {41857397},
issn = {1476-5578},
support = {82550005//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
abstract = {Alzheimer's disease (AD) is characterized by progressive synaptic failure, neuroinflammation, amyloid and tau pathology, yet effective disease-modifying therapies remain limited. Cannabidiol (CBD) has shown neuroprotective potential in AD, but its direct molecular targets and signaling mechanisms remain unclear. Here, we demonstrate that CBD ameliorates cognitive and emotional deficits in 3×Tg-AD mice by restoring synaptic integrity and plasticity. At the mechanistic level, CBD activated TrkB signaling independently of BDNF, leading to suppression of tau hyperphosphorylation via the PI3K/AKT/GSK3β pathway and attenuation of neuroinflammation and amyloid pathology through inhibition of the JAK2/STAT3/SOCS1 axis. Using isothermal shift assays combined with biophysical binding analyses, we identified FRS2, a core adaptor protein of TrkB, as a direct molecular target of CBD. Molecular dynamics simulations further revealed that CBD stabilizes the FRS2-TrkB interface, thereby facilitating TrkB activation. Importantly, genetic knockdown of FRS2 abolished CBD-induced TrkB signaling and its downstream neuroprotective effects in both cellular and in vivo AD models. Together, these findings identify FRS2 as a critical signaling node mediating BDNF-independent TrkB activation by CBD and establish a mechanistic framework linking CBD to disease-modifying pathways in AD.},
}

@article {pmid41857623,
year = {2026},
author = {Agosta, F and Cecchetti, G and Spinelli, EG and Ghirelli, A and Rugarli, G and Pisano, S and Coraglia, F and Canu, E and Castelnovo, V and Sibilla, E and Gilioli, A and Tripodi, C and Freri, F and Bianchi, A and Vezzulli, P and Calloni, S and Falini, A and Samanes Gajate, AM and Panzacchi, A and Pepe, G and Ferri, C and Chiti, A and Filippi, M},
title = {Real-world implementation of lecanemab and donanemab in an Italian memory center: a 1-year experience.},
journal = {Alzheimer's research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13195-026-02015-6},
pmid = {41857623},
issn = {1758-9193},
}

@article {pmid41857676,
year = {2026},
author = {Khurshid, Z and Tong, T and Olayinka, O and Farrell, JJ and Zhu, C and , and Martin, ER and Bush, WS and Pericak-Vance, MA and Wang, LS and Schellenberg, GD and Haines, JL and Lunetta, KL and Zhang, X and Farrer, LA},
title = {Interactive effects of telomere length and genetic variants on Alzheimer disease risk across multiple ancestral populations.},
journal = {Alzheimer's research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13195-026-02005-8},
pmid = {41857676},
issn = {1758-9193},
support = {U01-AG072577/AG/NIA NIH HHS/United States ; R01-AG048927/AG/NIA NIH HHS/United States ; },
}

@article {pmid41858054,
year = {2026},
author = {Reuben, DB and Chambliss, AB and Katz, BJ and López, AS and Hinman, JD},
title = {Rational Use of Blood-Based Biomarkers for Alzheimer's Disease: Navigating Between the Hope and the Hype.},
journal = {Journal of the American Geriatrics Society},
volume = {},
number = {},
pages = {},
doi = {10.1111/jgs.70384},
pmid = {41858054},
issn = {1532-5415},
abstract = {With better understanding of the pathologic processes of Alzheimer's disease, diagnostic methods have been developed to focus on specific biomarkers of disease detectable on brain imaging, cerebral spinal fluid, and, more recently, plasma. Although these tests do not establish a diagnosis of dementia, which requires a clinical evaluation, they can more precisely identify whether Alzheimer's disease is a contributing cause. The recent FDA approval of two blood-based biomarkers and the availability of others, including direct-to-consumer tests, has led to the potential for widespread use in primary and specialty care. However, the currently available blood-based biomarkers are more highly correlated with amyloid brain PET scans, which are less specific for symptomatic Alzheimer's disease, than with p-tau brain PET scans, which are strongly associated with changes in cognition. The value of a positive or negative blood-based biomarker depends on the test characteristics (e.g., sensitivity and specificity) of the specific test as well as the prevalence of the disease in the population. Clinicians ordering blood-based biomarkers must decide their value in the care of individual patients and be prepared to interpret the test results to their patients.},
}

@article {pmid41858070,
year = {2026},
author = {Zhang, Z and Fan, R and Jing, S and Liu, S and Liu, L and Que, W and Lu, D and Gan, Y and Xiao, F},
title = {Plasma proteomic trajectories before the onset of neurodegenerative diseases.},
journal = {Neurodegenerative disease management},
volume = {},
number = {},
pages = {1-12},
doi = {10.1080/17582024.2026.2646760},
pmid = {41858070},
issn = {1758-2032},
abstract = {BACKGROUND: The study aimed to identify indicative proteins associated with the occurrence and mortality of three neurodegenerative diseases (NDDs) and track the changes of proteins before the onset of NDDs.

RESEARCH DESIGN AND METHODS: We analyzed plasma proteomic data from UK Biobank. Cox regression analyses were utilized to detect the relationship between plasma proteins and the risk of development and all-cause mortality of Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Predictive models were established based on related proteins using Lasso regression.

RESULTS: We identified 14 disease-associated proteins for AD, 35 for PD, and one for ALS. The trajectory of plasma proteins before the onset of NDDs was portrayed. Neuroinflammation and the remodeling of the extracellular matrix might be common pathways for NDDs.

CONCLUSIONS: Our results highlighted that the landscape of plasma protein changes before the onset of NDDs.},
}

@article {pmid41858118,
year = {2026},
author = {Vogt, M and Helfenberger, N and Appenzeller-Herzog, C and Adlbrecht, L and Hirt, J},
title = {Non-pharmaceutical interventions for persons living with young-onset dementia and their informal caregivers: A systematic review with meta-analysis.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261429998},
doi = {10.1177/13872877261429998},
pmid = {41858118},
issn = {1875-8908},
abstract = {BackgroundYoung-onset dementia (YOD) causes major life disruptions and emotional strain for both persons living with YOD and their informal caregivers. Non-pharmaceutical interventions may help to improve quality of life and reduce stress.ObjectiveWe aimed at investigating the effects of non-pharmaceutical interventions for persons living with YOD and their informal caregivers and to explore the intervention characteristics.MethodsWe conducted a systematic review including randomized and non-randomized controlled trials (PROSPERO: CRD42025645744). We searched major bibliographic databases and performed citation and web searches. Two reviewers independently screened titles, abstracts, and full texts. For data extraction, we used Elicit, an artificial intelligent research assistant; with extractions confirmed by a human reviewer. The methodological quality was assessed using the Mixed Methods Appraisal Tool (MMAT). We performed a narrative synthesis based on a harvest plot. When appropriate, we performed meta-analyses.ResultsWe found 9 trials assessing interventions on education and information or skills building interventions that were published between 1990 and 2024 (median sample size: 58). Meta-analyses revealed no statistically significant impact on behavioral outcomes, activities of daily living, and quality of life of persons living with YOD and no statistically significant impact on burden, depression and anxiety, and quality of life of informal caregivers.ConclusionsEvidence on the effectiveness of non-pharmaceutical interventions for persons living with YOD and their informal caregivers is limited and inconsistent. Further, larger, and multiple randomized controlled trials assessing the impact of non-pharmaceutical interventions with comparable outcomes, standardized measurements, and longer follow-ups are needed.},
}

@article {pmid41858126,
year = {2026},
author = {Tolea, MI and Besser, LM and O'Shea, DM and Sol, K and Chrisphonte, S and Kleiman, MJ and Baig, MM and Joshi, MS and Galvin, JE},
title = {Associations between self-reported change in lifestyle behaviors and brain health: Findings from the Healthy Brain Initiative.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261432600},
doi = {10.1177/13872877261432600},
pmid = {41858126},
issn = {1875-8908},
abstract = {BackgroundHealthy lifestyles may reduce dementia risk by helping build cognitive reserve across the life course and promoting resilience and better cognitive outcomes in late-life. Whether self-reported lifestyle changes are informative for assessing brain health remains unclear.ObjectiveTo determine whether self-reported lifestyle changes (determinants) are associated with cognition, resilience, and Alzheimer's disease and related dementias (ADRD) biomarkers (outcomes), and whether these associations vary by sociodemographic characteristics and cognitive impairment status.MethodsData was obtained from 260 adults (age-range: 50-92). Self-reported change (increase/no change, decrease) in diet and physical, cognitive, and social activity from age 25 to present was evaluated in relation to cognition, resilience, and biomarkers within a cross-sectional design. ANCOVA models adjusted for age, sex, race, ethnicity, and education were used to examine associations between lifestyle change and outcomes. Effect modification by sex, race, ethnicity, and cognitive impairment status was also tested.ResultsSelf-reported increases in physical activity and diet were associated with better cognition and higher resilience, while increases in social activity with higher resilience and larger amygdala volume. Associations were stronger when increases occurred in multiple lifestyle domains. Associations differed by cognitive impairment status; no variation by sex and race was observed.ConclusionsIncreases in lifestyle behaviors relative to age 25 were associated with better cognitive and brain health outcomes, especially when increases occurred across multiple domains. These findings align with longitudinal evidence linking lifestyle engagement to cognitive aging and suggest that cross-sectional self-report of change may provide a useful proxy for estimating long-term lifestyle patterns.},
}

@article {pmid41858175,
year = {2026},
author = {Lin, CH and Wang, SH and Lane, HY},
title = {Sodium benzoate, a D-amino acids oxidase inhibitor, for the treatment of mild cognitive impairment: Pooled data from three randomized, double-blind, placebo-controlled trials.},
journal = {Psychiatry and clinical neurosciences},
volume = {},
number = {},
pages = {},
doi = {10.1111/pcn.70052},
pmid = {41858175},
issn = {1440-1819},
support = {DMR-115-102//China Medical University Hospital/ ; CMRPG8M1311//Kaohsiung Chang Gung Memorial Hospital/ ; CMRPG8M1361//Kaohsiung Chang Gung Memorial Hospital/ ; CMRPG8N1201//Kaohsiung Chang Gung Memorial Hospital/ ; CMRPG8N1121//Kaohsiung Chang Gung Memorial Hospital/ ; CMRPG8N1212//Kaohsiung Chang Gung Memorial Hospital/ ; NHRI-EX111-10816NC//National Health Research Institutes/ ; NHRI-EX113-11133NI//National Health Research Institutes/ ; NSTC 112-2314-B-039-020-MY3//National Science and Technology Council/ ; NSTC 113-2314-B-039-045-MY3//National Science and Technology Council/ ; NSTC 114-2314-B-182A-058-MY3//National Science and Technology Council/ ; NSTC 114-2622-B-039 -001//National Science and Technology Council/ ; NSTC 114-2629-B-039-001//National Science and Technology Council/ ; MOST 109-2628-B-182A-002//Ministry of Science and Technology, Taiwan/ ; MOST 111-2314-B-182A-024-MY3//Ministry of Science and Technology, Taiwan/ ; },
abstract = {BACKGROUND: Previous studies found that sodium benzoate (the pivotal D-amino acid oxidase [DAO] inhibitor) improved cognitive function in patients with mild Alzheimer's disease (AD); however, its efficacy for mild cognitive impairment (MCI) remained inconclusive. This study aims to evaluate the efficacy and safety of sodium benzoate in treating amnestic MCI (aMCI).

METHODS: Data were pooled from three randomized, double-blind, placebo-controlled trials. One hundred thirty-three patients with aMCI were enrolled from three major medical centers in Taiwan to receive 24-week treatment of 250-1500 mg/day of sodium benzoate or placebo. The cognitive outcome was Alzheimer's disease assessment scale-cognitive subscale (ADAS-cog), and the functional outcome was Instrumental Activities of Daily Living (IADL). Both were measured at weeks 0, 8, 16, and 24.

RESULTS: Among 133 participants, sodium benzoate therapy improved ADAS-cog scores more than placebo (P = 0.033 at week 16, 0.026 at week 24). Among 84 women, benzoate surpassed placebo in ADAS-cog (P = 0.046 at week 16, 0.029 at week 24), as well as IADL (P = 0.043 at week 24). In contrast, among 49 men, the two treatment groups did not differ significantly in both ADAS-cog and IADL scores. Both sodium benzoate and placebo were well tolerated and benzoate therapy produced no additional side effect.

CONCLUSIONS: This study is the first to demonstrate that a DAO inhibitor, sodium benzoate herein, can enhance overall cognitive function in MCI individuals. Furthermore, it can improve female patients' IADL. The finding lends support for DAO inhibition as a novel approach for early dementing processes.},
}

@article {pmid41858217,
year = {2026},
author = {Li, Y and Feng, J and Xie, Y and Yao, Q and Yu, J and Xu, S and Wang, Z and Wang, Q},
title = {Eye-brain coupling-mediated eye movement abnormalities as non-invasive biomarkers for mild cognitive impairment: A systematic review.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261430597},
doi = {10.1177/13872877261430597},
pmid = {41858217},
issn = {1875-8908},
abstract = {BackgroundEye movement abnormalities have emerged as promising non-invasive candidate biomarkers for the early detection, progression monitoring, and differential diagnosis of Alzheimer's disease (AD), with preliminary clinical evidence supporting their translational potential. Current AD diagnostic methods are limited by subjectivity, high cost, and complexity-making non-invasive biomarkers critical, especially for mild cognitive impairment (MCI). The tight functional link between the eye and brain underscores eye movement abnormalities as a window into AD-related pathology.ObjectiveThis systematic review summarizes AD-associated multi-modal eye movement dysfunctions (focusing on saccades, fixation, and smooth pursuit), clarifies their pathological mechanisms, clinical value, and translational feasibility, providing a basis for constructing an AD biomarker system.MethodsLiterature searches were conducted in PubMed, Web of Science, and Google Scholar using ("Alzheimer's disease" OR "mild cognitive impairment" AND "eye movements" OR "saccades" OR "smooth pursuit" OR "fixation") with a search cutoff date of September 30, 2025. Studies deemed irrelevant or lacking sufficient data were excluded.ResultsAD/MCI patients exhibit eye movement abnormalities: prolonged saccadic latency, increased antisaccade errors, reduced fixation stability, and attenuated smooth pursuit gain, which are closely linked to core AD pathologies, detectable in AD/MCI stages, and can, to a certain extent, distinguish AD from Parkinson's disease and frontotemporal dementia, and have value for MCI-to-AD conversion prediction.ConclusionsEye movement abnormalities hold promise as non-invasive biomarkers for AD, with potential for preclinical screening and differential diagnosis. To advance translation, future research should prioritize AI-driven multi-modal integration, standardized detection protocols, portable device development, and preclinical longitudinal validation.},
}

@article {pmid41858425,
year = {2026},
author = {Xu, M and Xiong, L and Qin, Z and Yu, X and Chen, T and Zhang, X and Jin, M and Wang, L and Cai, L and Wei, Y and Liu, H and Wang, C and Hu, H and Zou, Z},
title = {Epigenetic Changes in Alzheimer's Disease and Interventions for Therapy.},
journal = {Neuropsychiatric disease and treatment},
volume = {22},
number = {},
pages = {576404},
pmid = {41858425},
issn = {1176-6328},
abstract = {With the ageing of society, the number of Alzheimer's disease (AD) patients has increased rapidly, imposing a heavy burden on families and society. This article reviews the causes of AD, particularly the epigenetic changes associated with AD, including DNA methylation, histone modifications, and noncoding RNA changes. The development of diagnostic reagents based on biomarkers specific to epigenetic changes and attempts to intervene in adverse epigenetic factor changes in AD for the treatment of AD are discussed. This review contributes to a better understanding of the relationship between epigenetics and AD and provides guidance for exploring diagnostic and therapeutic strategies.},
}

@article {pmid41858499,
year = {2026},
author = {Barger, SW and Moerman-Herzog, AM},
title = {Modulation of apolipoprotein E receptor-2 by ApoE4, amyloid β-peptide, reelin, and secreted amyloid precursor protein: a common point of impact in Alzheimer's disease pathogenesis.},
journal = {Frontiers in molecular neuroscience},
volume = {19},
number = {},
pages = {1781541},
pmid = {41858499},
issn = {1662-5099},
abstract = {INTRODUCTION: Apolipoprotein E (ApoE), reelin, and several other proteins bind ApoE-receptor 2 (apoER2), distinguished from other members of its receptor family by signal transduction which enhances the activity of N-methyl D-aspartate (NMDA) receptors. Evidence indicates that this signal transduction depends upon apoER2 forming dimers or other high-order clusters. It seems noteworthy therefore that protein products of major APOE gene variants differ in their numbers of cysteines capable of forming disulfide dimers, with the allele (ε4) associated with highest rates of Alzheimer's disease (AD) possessing none. Thus, lower AD risk may be associated with the ability of ApoE to dimerize and thereby promote apoER2 dimerization and signaling.

METHODS: We examined calcium fluxes via the NMDA receptor in neurons derived from the NTera2 cell line in response to conditioned medium from human astrocytes differing in APOE genotype, recombinant ApoE proteins, reelin, amyloid β-peptide (Aβ) preparations differing in their aggregation states, and secreted amyloid precursor protein (sAPP). Signaling through apoER2 was inhibited by receptor-associated protein (RAP) or siRNA directed against apoER2.

RESULTS: Reelin, fibrillar Aβ, ApoE3, and conditioned medium from APOE ε3 astrocytes elevated calcium fluxes, and this phenomenon required apoER2. By contrast, ApoE4 and oligomeric Aβ antagonized activation. sAPP showed high-affinity binding to apoER2 and enhanced responses to reelin.

DISCUSSION: These findings suggest a comprehensive hypothesis for the pathogenesis of AD whereby the common factor in development of disease is antagonism of apoER2, likely to include agents that cannot promote the receptor's dimerization yet competitively inhibit those ligands that can cause dimerization.},
}

@article {pmid41858558,
year = {2026},
author = {Tran, MH and Pruitt, K and Bryarly, M and Emordi, I and Ali, A and Ma, L and Fei, B},
title = {Development and validation of a high-resolution hyperspectral imaging system for the retina.},
journal = {Journal of biomedical optics},
volume = {31},
number = {3},
pages = {036006},
pmid = {41858558},
issn = {1560-2281},
mesh = {Animals ; *Hyperspectral Imaging/methods/instrumentation ; Mice ; *Retinal Vessels/diagnostic imaging ; Algorithms ; Phantoms, Imaging ; *Retina/diagnostic imaging ; *Image Processing, Computer-Assisted/methods ; Oxygen/metabolism ; Deep Learning ; Mice, Inbred C57BL ; },
abstract = {SIGNIFICANCE: Early detection of Alzheimer's diseases, diabetic retinopathy, or macular degeneration with advanced retinal imaging technologies can help improve patient care and treatment outcome.

AIM: We aim to create a high-resolution hyperspectral imaging (HSI) system for the retina. Retinal vessel diameter and oxygenation rate will be extracted simultaneously from HSI data.

APPROACH: Our hyperspectral retinal imaging system consists of a snapshot hyperspectral camera, a high-resolution RGB camera, a beamsplitter, and an imaging endoscope. Multiple pansharpening algorithms, including deep learning methods, were developed to generate high-resolution hyperspectral images that were further used for the measurement of vessel size and oxygenation rate in mice.

RESULTS: The hyperspectral retinal imaging system was tested for its spatial resolution and spectral fidelity in retina phantoms. In vivo imaging experiments were performed in mice. The deep learning-based pansharpening algorithm achieved a root mean square error (RMSE) of 2.15 ± 0.64 , a correlation coefficient (CC) of 0.96 ± 0.05 , a spectral angle score of 0.06 ± 0.03 radians, and an error relative global dimensionless synthesis (ERGAS) score of 2.37 ± 1.71 . Oxygen saturation (sO 2) and lumen diameters of blood vessels were measured in the retina. The average lumen diameter of the venules was 45.7 ± 13.6    μ m , whereas the average lumen diameter of the arterioles was 31.5 ± 8.7    μ m . The average arteriole sO 2 was 98%, whereas the average venule sO 2 was 58%.

CONCLUSIONS: A high-resolution hyperspectral imaging system was developed and validated for retina imaging and measurement of blood vessels and oxygen saturation.},
}

Animals
*Hyperspectral Imaging/methods/instrumentation
Mice
*Retinal Vessels/diagnostic imaging
Algorithms
Phantoms, Imaging
*Retina/diagnostic imaging
*Image Processing, Computer-Assisted/methods
Oxygen/metabolism
Deep Learning
Mice, Inbred C57BL

@article {pmid41858787,
year = {2026},
author = {Cao, H and Liang, J and Dong, X and Xia, Z and Luo, X and Liu, B},
title = {Targeting the astrocytic metabolic cascade in Alzheimer's disease: mechanisms, challenges and opportunities.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1767811},
pmid = {41858787},
issn = {1663-4365},
abstract = {Alzheimer's disease (AD), a pressing global public health challenge, is underpinned by multifaceted pathogenic mechanisms. While traditional research has centered on amyloid-β deposition and tau hyperphosphorylation, emerging evidence reveals that metabolic perturbations play a pivotal role in the earliest phases of AD. As the principal regulators of energy homeostasis within the central nervous system, astrocytes orchestrate a multistep metabolic cascade-encompassing glucose uptake, glycolysis, mitochondrial oxidative metabolism, and the release of metabolic intermediates-to sustain neuronal energy supply and synaptic integrity. In the AD milieu, this astrocytic metabolic cascade becomes profoundly disrupted at every level. Such metabolic dysregulation not only compromises the neuroprotective functions of astrocytes but also directly accelerates synaptic degeneration, exacerbates Aβ and tau pathologies, and amplifies neuroinflammatory responses, collectively forming a core "metabolic-neurodegeneration" pathological axis. Here, we provide a comprehensive synthesis of the aberrant astrocytic metabolic cascade in AD, delineating its critical contributions to synaptic deterioration, proteinopathy progression, and inflammatory escalation. Building on these insights, we propose a conceptual model of an "astrocyte-centric metabolic collapse," highlighting metabolic derailment as a fundamental initiating and amplifying force in AD pathogenesis. Furthermore, we evaluate therapeutic strategies targeting key nodes of this cascade and discuss the challenges and opportunities inherent in modulating astrocytic metabolism. Through integrating the most recent advances, this review offers a refined understanding of astrocytic metabolic dysregulation in AD and examines its potential as a promising avenue for therapeutic intervention.},
}

@article {pmid41858791,
year = {2026},
author = {Su, CW and Chen, K and Wu, T and Reiman, EM and Wang, Q},
title = {TAS2R38 taster variants-linked MGAM expression in Alzheimer's disease: a novel target for precision drug repurposing.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1768436},
pmid = {41858791},
issn = {1663-4365},
abstract = {INTRODUCTION: TAS2R38 is a taste receptor gene located on human chromosome 7 that influences sensitivity to bitter tastes and has been implicated in innate immunity, glucose level, and human longevity. However, its potential association with Alzheimer's Disease (AD) has not been explored. Identifying such a genetic connection could support developing new drugs or repurposing existing ones for AD treatment.

METHODS: In this work, we examined the relationship between allele counts of TAS2R38 taster variants and AD risk using linear mixed-effects models, utilizing genetic, clinical, and biomarker data from the Alzheimer's Disease Neuroimaging Initiative (ADNI). We investigated the potential molecular mechanisms of the association by identifying expression quantitative trait loci (eQTLs) using RNA-seq data from postmortem tissues across brain regions from the Religious Orders Study/Memory and Aging Project (ROSMAP). We evaluated whether FDA-approved drugs targeting the identified e-gene could reduce dementia risk using 1:1 propensity score-matched groups from longitudinal data in the National Alzheimer's Coordinating Center (NACC) study, by comparing clinical dementia progression trends between the drug-taking and non-taking groups with linear mixed-effects models.

RESULTS: Our results show that TAS2R38 supertasters were connected to a reduced AD risk with advancing age due to its association with various AD biomarkers (p < 0.001). eQTL analysis linked the nontaster allele to increased expression of the gene MGAM in AD-affected brain regions (p < 0.001). Furthermore, elevated MGAM expression correlated with more severe Tau burden (p < 0.05) and implicated in mitochondrial dysfunction in AD subjects. Notably, MGAM is a known drug target for diabetes mellitus. In NACC data, individuals taking MGAM-inhibiting drugs (acarbose and miglitol) showed slower clinical dementia rating progression (p < 0.01) in comparison with the non-taking group.

DISCUSSION: This study is the first to report a genetic association between TAS2R38 and AD biomarkers. Our findings, validated in multiple cohorts/matching groups, suggest MGAM as a novel AD drug target with existing FDA-approved inhibitors and demonstrate the potential of TAS2R38 haplotypes to inform precision drug repurposing strategies for AD, which warrants further in-depth preclinical and clinical studies.},
}

@article {pmid41858792,
year = {2026},
author = {Raber, J and Sharpton, TJ},
title = {Diet, gut microbiome, and cognition in neurodegeneration: a review and methodological framework.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1771904},
pmid = {41858792},
issn = {1663-4365},
abstract = {The gut microbiome influences brain function through the gut-brain axis via synthesis of neurotransmitters, production of metabolites affecting epithelial barrier integrity and immune modulation and signaling through the vagus nerve. In humans, microbiome diversity reflects healthy aging and predicts survival, while dysbiosis is increasingly implicated in neurodegenerative conditions including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and ALS. Fecal transplant studies in germ-free mice demonstrate that microbiome alterations are sufficient to induce cognitive and neuropathological phenotypes, supporting causality in preclinical models. Genetic risk factors and environmental exposures affect both neurodegeneration risk and microbiome composition. In this review, we synthesize evidence from human cohorts and preclinical models on the gut-brain axis in cognitive health and disease. We then present a methodological framework for diet-microbiome-cognition research, addressing causal inference through mediation analysis, supervised approaches for deriving diet scores, validation strategies, and individual heterogeneity. This framework can guide development of microbiome-targeted dietary interventions to improve cognitive outcomes.},
}

@article {pmid41858793,
year = {2026},
author = {Wang, R and Feng, Y and Zhou, Z and Jiang, J and Zhang, R and Zou, W and Yang, H and Lv, W and Yang, S},
title = {Emerging pathological mechanisms of Alzheimer's disease pathogenesis: from neuroimmune interactions to intercellular communication.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1748418},
pmid = {41858793},
issn = {1663-4365},
abstract = {Alzheimer's disease (AD) research has transcended the traditional paradigm centered on amyloid-beta (Aβ) shifting toward a neuroimmune network perspective. This article systematically elucidates the evolving mechanisms underlying disease progression, from neuroimmune interactions to intercellular communication. Studies indicate that microglial and astrocytic dysfunctions are key contributors to disease progression, operating within a complex multifactorial framework. Upon transformation into disease-associated microglia (DAM), microglia exhibit a significant decline in Aβ clearance capacity and release a plethora of pro-inflammatory factors, exacerbating neuroinflammation and neuronal damage. Concurrently, astrocytes lose their homeostatic support functions and acquire neurotoxic properties. Intercellular communication molecules play pivotal roles as key mediators. The cytokine/chemokine network sustains a chronic inflammatory milieu; extracellular vesicles (EVs) facilitate the propagation of Aβ and tau pathologies; and the complement system (e.g., C1q) transitions from physiological synaptic pruning to pathological synaptic engulfment. Furthermore, peripheral immune cell infiltration and gut-brain axis dysregulation further expand the pathological scope. Consequently, therapeutic strategies are evolving towards multi-target interventions, including precise immune modulation (e.g., TREM2 agonists), exosome-based drug delivery systems, and combination therapies. Addressing disease heterogeneity and developing personalized treatments are critical future directions. Ultimately, early interventions aimed at restoring healthy intercellular communication offer new hope for halting AD progression.},
}

@article {pmid41858824,
year = {2026},
author = {Fu, W and Wang, K and Chen, H and Liu, T and Liu, X and Jin, Q and Tan, Z and Dong, W and Liu, W and Sang, Z},
title = {Design, synthesis and biological evaluation of novel 3,4-dihydro-2(1H)-quinoline-O-carbamate derivatives as AChE/MAO-B dual inhibitors for the treatment of Alzheimer's disease.},
journal = {RSC medicinal chemistry},
volume = {},
number = {},
pages = {},
pmid = {41858824},
issn = {2632-8682},
abstract = {Alzheimer's disease (AD) is an irreversible degenerative disorder of the brain, and there is no effective drug for it to date. Given its complex pathogenesis, the multi-target-directed ligand (MTDL) strategy is considered as a promising approach against AD. Herein, a series of 3,4-dihydro-2(1H)-quinoline-O-carbamate derivatives were designed and synthesized based on the MTDL strategy. The in vitro biological results indicated that 3c was a potent AChE/MAO-B dual inhibitor with an IC50 value of 0.81 μM and 0.17 μM, respectively. Molecular modeling and molecular dynamics (MD) simulations offered possible insights into the AChE/MAO-B inhibition of 3c. Moreover, 3c showed good stability and BBB permeability, as well as favorable neuroprotective effects. In vivo evaluation exhibited that 3c impressively improved the AlCl3-induced zebrafish AD model by elevating ACh, decreasing APP and inflammatory factors. Further, 3c effectively alleviated the scopolamine-induced cognitive impairment model. Therefore, 3c is a promising AChE/MAO-B dual inhibitor for treating AD.},
}

@article {pmid41858835,
year = {2026},
author = {Khan, FA and Khan, H and Awan, UA and Nurahmat, M and Nabijan, M and Abduwaki, M and Dong, J},
title = {c-Jun in neurodegeneration: A key transcriptional regulator with therapeutic implications.},
journal = {Molecular therapy. Nucleic acids},
volume = {37},
number = {2},
pages = {102874},
pmid = {41858835},
issn = {2162-2531},
abstract = {c-Jun, a core component of the activating protein-1 (AP-1) transcription factor complex, regulates cellular processes including proliferation, differentiation, survival, apoptosis, and oncogenesis. c-Jun functions by dimerizing to bind DNA and modulates the expression of genes such as Bcl-2, cyclin D1, and pro-inflammatory cytokines, enabling context-dependent transcriptional control. Its role in neurodegenerative diseases has gained attention due to its regulation of oxidative stress, inflammation, and apoptosis. In Parkinson's disease, Alzheimer's disease, and Huntington's disease, dysregulated c-Jun expression accelerates dopaminergic neuron loss via oxidative damage, contributes to amyloid-β-induced synaptic toxicity, and mediates neuronal apoptosis and inflammation, respectively. Despite its degenerative role, c-Jun also promotes axonal regeneration and stress adaptation, revealing a dual function that depends on context and stimulus severity. This paradox underscores its ability to promote survival under mild stress and apoptosis under chronic damage. Emerging therapeutic strategies targeting c-Jun-via small-molecule inhibitors (e.g., SP600125), RNA interference, or modulation of upstream c-Jun N-terminal kinase (JNK)-are being explored. However, challenges remain in achieving specificity, as c-Jun's ubiquitous expression raises concerns about off-target effects. This review highlights recent advances in understanding c-Jun's complex role in neurodegeneration and its therapeutic potential, emphasizing its value as both a mechanistic regulator and a target for preserving neuronal integrity in neurodegenerative diseases.},
}

@article {pmid41858884,
year = {2026},
author = {Davargaon, RS and Verma, N and Kotiya, D and Leibold, N and Velmurugan, GV and Coburn, H and Chen, KC and Ruiz, D and Corces, V and Liu, H and Kachroo, P and Singh, PK and Gentry, MS and Despa, S and Despa, F},
title = {Peripheral amylin modulation rebalances brain glycolysis and Tau-Ser214 phosphorylation via cAMP-PKA signaling.},
journal = {iScience},
volume = {29},
number = {3},
pages = {115157},
pmid = {41858884},
issn = {2589-0042},
abstract = {Brain glucose dysregulation is shared by Alzheimer's disease (AD) and diabetes, but whether it arises from central or peripheral mechanisms remains unclear. Amylin, a pancreatic hormone, normally supports CNS cAMP-PKA signaling, metabolism and memory; however, prediabetes-associated hypersecretion disrupts this balance. Using human amylin-inducible mice, we show that toggling amylin secretion during metabolic stress bidirectionally regulates brain glycolysis and function. Excess amylin overactivates cAMP-PKA signaling, suppressing glycolysis and inducing Tau-Ser214 phosphorylation, two core features of AD pathology. This state is accompanied by activation of the amino acid starvation response, Tau-T231 hyperphosphorylation, pTau-Aβ coupling, neuroinflammation and memory deficit. In contrast, reducing amylin in prediabetes preserves glycolysis, ATF4-dependent proteostasis and cognition. Astrocytes emerge as primary targets, as amylin receptor blockade prevents glycolytic deficits ex vivo, and amylin accumulates in GFAP-enriched regions in vivo. Together, these results define prediabetic hyperamylinemia as an upstream, modifiable driver of PKA-mediated tau pathology linking metabolic dysfunction to AD.},
}

@article {pmid41859113,
year = {2026},
author = {Devine, J and Jacobs, B and Leroux-Roels, I and Leroux-Roels, G and van der Most, R},
title = {Infection, vaccination and risk of dementia: a proposed immunological model.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1748535},
pmid = {41859113},
issn = {1664-3224},
mesh = {Humans ; *Dementia/immunology/epidemiology/etiology/prevention & control ; *Vaccination ; *Models, Immunological ; BCG Vaccine ; Alzheimer Disease/immunology ; Immunity, Innate ; Risk Factors ; SARS-CoV-2/immunology ; Adjuvants, Immunologic ; },
abstract = {With ageing populations, the prevalence of different types of dementias is increasing. The pathology of Alzheimer's disease (AD), the most common form of dementia, has been linked to the presence of plaques and neurofibrillary tangles in the central nervous system of patients. There are growing indications that risk of developing dementia correlates with several infectious agents, including human herpes viruses, flaviviruses and SARS-CoV-2. This has led to a proposition that AD and other dementias could be considered as having an infectious disease etiology. Whilst the mechanisms behind this remain unclear, intriguing epidemiological data suggest that several vaccinations are correlated with reduced risk for dementia. Intravesicular administration of the tuberculosis vaccine strain Bacille Calmette-Guérin (BCG) has been associated with decreased risk of dementia in bladder cancer patients. This has led to the hypothesis that non-specific effects of vaccinations, mediated through trained innate immunity, provide a mechanistic explanation. Over the last few years, the AS01-adjuvanted recombinant shingles vaccine has also been associated with reduced risk in several studies. Moreover, in a recent study, immunization with the adjuvanted RSV vaccine, also containing AS01, was shown to reduce risk of dementia. Integrating data on BCG and mechanistic hypotheses, recent findings on the AS01 adjuvant, and the role of trained innate immunity, we describe here an immunological model that connects vaccine and adjuvant mode of action with risk of dementia. This immunological model can help shape a research roadmap to further elucidate the mechanisms behind the collective epidemiological data.},
}

Humans
*Dementia/immunology/epidemiology/etiology/prevention & control
*Vaccination
*Models, Immunological
BCG Vaccine
Alzheimer Disease/immunology
Immunity, Innate
Risk Factors
SARS-CoV-2/immunology
Adjuvants, Immunologic

@article {pmid41859188,
year = {2026},
author = {Nwulia, E and Ajibade, TO and Onukak, CE and Esan, OO and Abiola, JO and Omobowale, TO and Olaifa, OS and Alaka, OO and Igado, OO and Obasa, AA and Ana, G and Omobowale, OC and Hipolito, M and Awofeso, OM and Idowu, A and Oyagbemi, AA},
title = {Toxicological effects of volatile organic compounds are mediated by aggravated oxidative stress and neuroinflammatory processes in piglets.},
journal = {Toxicology reports},
volume = {16},
number = {},
pages = {102236},
pmid = {41859188},
issn = {2214-7500},
abstract = {Anthropogenic and natural sources of volatile organic compounds (VOCs) have been associated with hematological, cardiovascular, and respiratory diseases. VOCs can also track directly from the nose to the olfactory bulb (OB). This study investigated whether inhaled VOC-induced toxicity increases free radical generation and oxidative stress biomarker levels along the olfactory neural pathway from the nasal mucosa to brain regions implicated in Alzheimer's disease. In this study, twenty male six-week-old Landrace piglets were randomly divided into three groups and daily exposed to VOCs for eight weeks: Group A (unexposed piglets; n = 6), Group B (2 h exposure; n = 7), and Group C (3 h exposure; n = 7). The VOC mixture consisted of 5% formaldehyde, 5% benzene, 10% toluene, 10% xylene, and 70% water, and released at a steady-state Total VOC (TVOC) level of 1.0 mg/m3 range (0.6 - 1.8 mg/m3) in the test room. Biomarkers of oxidative stress, antioxidant status, and pro-inflammatory cytokines were assessed in the nasal mucosa, olfactory bulb, pyriform cortex, entorhinal cortex, and hippocampus. Exposure of piglets to VOCs significantly elevated malondialdehyde, hydrogen peroxide (H2O2) generation, nitric oxide, and acetylcholinesterase (AChE) activity along the contiguous olfactory neural structures, from the olfactory mucosa in the nose to the olfactory cortex and adjoining hippocampus. There was also a time-dependent significant reduction in glutathione content, superoxide dismutase levels, and glutathione S-transferase activities in the olfactory regions of VOCs-exposed piglets. Olfactory neuroinflammation was evidenced by significant elevations of IL-6, IL-8, IFNγ, and TNF-α. In summary, exposure of piglets to volatile organic compounds resulted in a significant elevation of biomarkers of oxidative stress and pro-inflammatory cytokines, and in depletion of the neuronal and systemic antioxidant defense systems. Furthermore, the observed olfactory neurotoxicity and neuroinflammation were more pronounced and prolonged after three hours of exposure to volatile organic compounds. Parallel patterns of neurotoxicity in the nasal-olfactory mucosa and the olfactory cortex suggest that the nose could serve as a window into pathophysiologic events underlying neurodegenerative diseases.},
}

@article {pmid41859231,
year = {2026},
author = {Xiaoyi, Z and Haixiao, L and Houjian, R and Wenya, Z and Jie, F and Han, S and Defeng, W and Zhen, W and Jingrong, C},
title = {The correlation and gut microbial characteristics in the whole spectrum of Alzheimer's disease: a systematic review and meta-analysis.},
journal = {Frontiers in neuroscience},
volume = {20},
number = {},
pages = {1775002},
pmid = {41859231},
issn = {1662-4548},
abstract = {BACKGROUND: Gut dysbiosis is hypothesized to be a potential pathological mechanism in patients across the Alzheimer's disease (AD) spectrum. Nevertheless, despite growing interest, existing findings remain largely inconsistent.

PURPOSE: This systematic review and meta-analysis aimed to compare the composition of gut microbiota (GM) between patients with mild cognitive impairment (MCI) or AD and healthy controls (HC).

METHODS: PubMed, Embase, MEDLINE and Web of science were searched from January 2022 to November 2025. Eligible studies included observational studies and pre-intervention arms of interventional trials reporting GM abundance in AD spectrum patients vs. HC. Two reviewers independently screened articles, extracted data, and assessed bias risk. Effect sizes were pooled using an inverse-variance weighted random-effects model.

RESULTS: Twenty studies (1,025 HC and 456 AD spectrum patients) were analyzed. AD patients demonstrated reduced GM diversity vs. HC cohort. The abundances of Megamonas and Bacteroides were elevated in AD patients, while Firmicutes and Proteobacteria were reduced. When stratified by clinical stage, Fusobacteria and Lactobacillus abundances showed gradient shift from MCI to AD.

CONCLUSION: Individuals within the AD spectrum exhibit altered GM abundance, with these differences influenced by clinical stage. The present study did not identify any significant trends; it reports only findings that have been statistically substantiated.},
}

@article {pmid41859400,
year = {2026},
author = {Maskey, D and Nguyen-Hao, HT and Smith, CC and Novelli, M and Stevens, J and Sutherland, GT},
title = {Antibody elution methods for multiplex immunofluorescence of Alzheimer's disease pathology in human post-mortem brain tissue.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1760600},
pmid = {41859400},
issn = {1664-2295},
abstract = {INTRODUCTION: Post-mortem human brain banks are a key resource for researching brain diseases. The New South Wales Brain Tissue Resource Center (BTRC) is a brain bank that focuses on neurodegenerative diseases, including alcohol use disorder and Alzheimer's disease. Most banks hemi-sect brains, freezing one half and fixing the other. Traditionally, formalin-fixed, paraffin-embedded tissue has been used for immunostaining, whereas frozen tissue has been used for complementary molecular studies. Immunofluorescent staining has been more difficult to employ than chromogen-based immunostaining in post-mortem brain tissue because of autofluorescence that is amplified further in archival tissue kept in formalin for long term storage. Multiplex immunofluorescence (mIF) is extremely useful for visualizing complex cell interactions in the brain but is limited by the availability of primary-secondary antibody combinations. Tyramide signal amplification (TSA) systems largely solved the latter issue but remains expensive to perform.

METHODS AND RESULTS: Given the increasing interest in human post-mortem brain tissue for mechanistic studies, we explored whether modifying stripping protocols for traditional mIF staining could improve performance to match newer TSA-based methods.

CONCLUSION: Employing β-mercaptoethanol (BME)-containing stripping buffer instead of heat-induced epitope retrieval gave similar results for both techniques in both short-term and long-term fixed tissue. However, iterative imaging sessions between cycles for traditional mIF still pose a greater risk for malalignment of target molecules in composite images.},
}

@article {pmid41859403,
year = {2026},
author = {Dong, Q and Li, J and Guo, X and Gao, Z and Liu, Z and Zhao, D and Ji, Z},
title = {Characteristics of brain computed tomography in dementia with cardiovascular disease and psychological and behavioral symptoms.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1714782},
pmid = {41859403},
issn = {1664-2295},
abstract = {OBJECTIVE: To describe brain computed tomography (CT) features in Alzheimer's disease (AD) with comorbid cardiovascular diseases (CVDs) and examine associations with behavioral and psychological symptoms (BPSD).

METHODS: This single-center, hospital-based observational case-control study (August 2019-May 2021) used consecutive sampling. We enrolled 165 older adults with AD and CVDs (CVD group), 165 older adults with AD without CVDs (AD-only group), and 165 cognitively healthy older adults (healthy controls). All participants underwent non-contrast brain CT at baseline. Qualitative CT findings [cortical atrophy, widened sulci, and medial hippocampal cerebrospinal fluid (CSF) pool widening] and quantitative parameters (lateral split brain width, frontal sulcus width, lateral ventricle width, third ventricle width, forehead index, and caudate nucleus index) were compared across groups. Diagnostic performance for AD (AD groups vs. healthy controls) was evaluated using receiver operating characteristic (ROC) curves and the area under the curve (AUC). BPSD were assessed with the Neuropsychiatric Inventory Questionnaire (NPI-Q), and correlations between NPI-Q scores and CT parameters were analyzed in the CVD group.

RESULTS: Qualitative CT abnormalities were more frequent in both AD groups than in healthy controls (p < 0.05) but did not differ between the CVD and AD-only groups (p > 0.05). Quantitative CT parameters showed a similar pattern: both AD groups differed from healthy controls (p < 0.05), while comparisons between the two AD groups were not significant (p > 0.05). The combined diagnostic AUC for AD was 0.881. In the CVD group, higher NPI-Q total scores were associated with decreased lateral split brain width and increased frontal sulcus width, lateral ventricle width, third ventricle width, forehead index, and caudate nucleus index (all p < 0.05).

CONCLUSION: AD participants, with or without CVD comorbidity, showed significant CT abnormalities compared with healthy controls. In AD with CVDs, quantitative CT parameters were associated with BPSD severity.},
}

@article {pmid41859452,
year = {2026},
author = {Jia, C and Zhu, W and Yuan, Y and Xie, Q},
title = {How gut microbiota contribute to neuropsychiatric disorders: evidence from neuroimaging studies.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1760096},
pmid = {41859452},
issn = {1664-302X},
abstract = {The interaction between the gut microbiota and central nervous system (CNS) diseases has emerged as a major focus in neuroscience and microbiome research. Accumulating evidence shows that gut microbiota influence the pathogenesis of neurodevelopmental, neurodegenerative, autoimmune, and psychiatric conditions via the microbiota-gut-brain axis. However, the underlying mechanisms are complex and not yet fully elucidated. Advances in multimodal magnetic resonance imaging, positron emission tomography, and diffusion tensor imaging, now enable in vivo visualization of associations between gut microbial alterations and abnormalities in brain structure and function, providing new perspectives for understanding the role of gut microbiota in CNS pathology. This review systematically reviews neuroimaging-based research linking gut microbiota to neurological diseases (e.g., Alzheimer's disease, multiple sclerosis, traumatic brain injury), and psychiatric disorders (e.g., schizophrenia, and autism spectrum disorder). It highlights the mediating roles of microbial metabolites, immune-inflammatory responses, and neuroimmune pathways, and discusses future directions integrating multi-omics data with neuroimaging technologies, as well as their potential clinical applications. What distinguishes this review from its predecessors in the same field is its explicit neuroimaging-driven framework rather than general mechanistic discussion.},
}

@article {pmid41859472,
year = {2026},
author = {Taylor, JS and Vig, EK},
title = {The nearness of the state: substitution practices at the ragged ends of life in the U.S.},
journal = {BioSocieties},
volume = {21},
number = {1},
pages = {83-99},
pmid = {41859472},
issn = {1745-8552},
abstract = {This essay examines two stories emerging from two different research projects, both based in Seattle, Washington (U.S.): one woman's story of her efforts to implement her husband's wishes following a stroke, and another woman's story of a failed suicide attempt by her dear friend who had been diagnosed with early-onset Alzheimer's disease. We first consider these stories in relation to the concept of substituted judgment implicit in the influential discourse of advance care planning (ACP). We then consider them in light of the concepts of 'substitution practices' and 'nearness' as developed by Mette Nordahl Svendsen. We contend that these concepts open valuable new perspectives and questions about medical decision-making and care in situations of grave impairment in late life. In particular, they help direct attention to the nearness of the state at the ragged ends of life, and indeed allow the situation of vulnerable and gravely impaired individuals to serve as a window onto what 'the state' is understood to be and do.},
}

@article {pmid41859568,
year = {2025},
author = {Adnan, D and Engen, PA and Villanueva, M and Raeisi, S and Ramirez, V and Naqib, A and Green, SJ and Bishehsari, F and Barnes, LL and Keshavarzian, A and Dhana, K and Voigt, RM},
title = {Oral microbiome brain axis and cognitive performance in older adults.},
journal = {NPJ dementia},
volume = {1},
number = {},
pages = {},
pmid = {41859568},
issn = {3005-1940},
abstract = {The human oral microbiota is a community of microorganisms that reside in the oral cavity, including lingual, buccal, and saliva, each niche with a distinct microbial composition. Alterations in oral microbiota have been associated with an increased risk of Alzheimer's disease (AD). This study used data from 143 older adults in the MIND trial to evaluate the association between oral microbiome and cognitive function. Oral niche-specific differences (saliva, buccal, and lingual), as well as the microbiome composition differences (α and β diversity), were associated with cognitive function. A lower abundance of Gemella and a higher abundance of anaerobic pro-inflammatory bacteria (e.g., Parvimonas, Treponema, Dialister) were linked to a lower Cognitive Z Score. Porphyromonas, previously linked to AD, was not associated with cognition. The outcomes suggest that oral microbiota may be a biomarker for cognitive function. Further research is required to assess whether oral microbiota-directed strategies can positively impact cognitive decline.},
}

@article {pmid41859776,
year = {2026},
author = {Wagemann, O and Götz, C and Wlasich, E and Sandkühler, K and Prix, C and Stockbauer, A and Marth, L and Jäck, A and Halbgebauer, S and Tumani, H and Höglinger, GU and Levin, J and Nübling, G},
title = {Combining blood biomarkers and the German version of the Dementia Screening Questionnaire for Individuals with Intellectual Disabilities (DSQIID-G) for diagnosing cognitive decline in Down syndrome.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {3},
pages = {e71296},
doi = {10.1002/alz.71296},
pmid = {41859776},
issn = {1552-5279},
support = {//Verum Foundation/ ; 2022_EKEA.133//Else Kröner-Fresenius-Stiftung/ ; CLINSPECT-M (FKZ161L0214B)//Bundesministerium für Bildung und Forschung (BMBF) project CLINSPECT-M/ ; FKZ161L0214C//Bundesministerium für Bildung und Forschung (BMBF) project CLINSPECT-M/ ; //Germany's Excellence Strategy within the framework of the Munich Cluster for Systems Neurology/ ; },
mesh = {Humans ; *Down Syndrome/complications/blood ; Female ; Male ; Biomarkers/blood ; *Neurofilament Proteins/blood ; Middle Aged ; *Cognitive Dysfunction/diagnosis/blood ; Surveys and Questionnaires ; *Glial Fibrillary Acidic Protein/blood ; Germany ; *Intellectual Disability/blood/complications ; Aged ; *Dementia/diagnosis/blood ; Adult ; },
abstract = {INTRODUCTION: Individuals with Down syndrome (DS) are at risk for Alzheimer's disease (AD). However, diagnosis remains challenging due to variability of intellectual ability and symptom presentation. To investigate whether serum AD biomarkers enhance accuracy of the German version of the Dementia Screening Questionnaire for Individuals with Intellectual Disabilities (DSQIID-G), we combined test scores with neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) levels.

METHODS: Seventy-eight DS individuals (49% female) completed the DSQIID-G; previous cohort data were added for a pooled sample (n = 164, 47% female). Serum NfL and GFAP were assessed using the automated microfluid Ella system.

RESULTS: Combining the DSQIID-G with NfL or GFAP resulted in improved accuracy in every diagnostic subgroup. The Youden index in the pooled samples yielded a cut-off score at 6.5.

DISCUSSION: The DSQIID-G is a robust screening tool and its combination with AD blood biomarkers aids earlier identification of individuals requiring further diagnostics for DS-associated AD.},
}

Humans
*Down Syndrome/complications/blood
Female
Male
Biomarkers/blood
*Neurofilament Proteins/blood
Middle Aged
*Cognitive Dysfunction/diagnosis/blood
Surveys and Questionnaires
*Glial Fibrillary Acidic Protein/blood
Germany
*Intellectual Disability/blood/complications
Aged
*Dementia/diagnosis/blood
Adult

@article {pmid41859874,
year = {2026},
author = {Gutstein, DB and Iorga, M and Stocks, J and Gill, N and Sleeman, J and Gefen, TD and Los, M and Nelson, C and Geula, C and Weintraub, S and Parrish, T and Mesulam, MM and Barbieri, E},
title = {Identifying neuropathologic disease in primary progressive aphasia using narrative speech.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {3},
pages = {e71294},
doi = {10.1002/alz.71294},
pmid = {41859874},
issn = {1552-5279},
support = {5R01AG077444/NH/NIH HHS/United States ; P30AG072977/NH/NIH HHS/United States ; P30AG013854/NH/NIH HHS/United States ; R01AG062566/NH/NIH HHS/United States ; //Karen Toffler Charitable Trust/ ; },
mesh = {Humans ; *Aphasia, Primary Progressive/pathology/diagnosis ; Male ; Female ; *Alzheimer Disease/pathology/diagnosis ; Aged ; *Narration ; Machine Learning ; *Natural Language Processing ; *Frontotemporal Lobar Degeneration/pathology/diagnosis ; *Speech ; Middle Aged ; Artificial Intelligence ; Tauopathies/pathology/diagnosis ; *Brain/pathology ; },
abstract = {INTRODUCTION: We present an application of artificial intelligence to narrative speech with the primary objective of predicting neuropathologic disease underlying primary progressive aphasia (PPA).

METHODS: Using natural language processing toolkits, features were extracted from transcribed narratives of the Cinderella story. Machine learning ensemble models classified participants as either normal controls (NC) or as individuals with PPA and a subsequent autopsy-confirmed neuropathologic diagnosis of either Alzheimer's disease (AD) or 4-repeat tauopathy under the umbrella of frontotemporal lobar degeneration (FTLD-4Rtau).

RESULTS: All models successfully distinguished transcribed narratives of AD from those with FTLD-4Rtau, as well as the narratives of NC from those with PPA. Feature permutation revealed diverging patterns of contribution to classification depending upon language domain and disease pathology.

DISCUSSION: The usage of artificial intelligence in the context of naturalistic language tasks may ultimately serve as a complementary aid in differential diagnosis of PPA disease pathologies and in uncovering avenues for disease-specific interventions.},
}

Humans
*Aphasia, Primary Progressive/pathology/diagnosis
Male
Female
*Alzheimer Disease/pathology/diagnosis
Aged
*Narration
Machine Learning
*Natural Language Processing
*Frontotemporal Lobar Degeneration/pathology/diagnosis
*Speech
Middle Aged
Artificial Intelligence
Tauopathies/pathology/diagnosis
*Brain/pathology

@article {pmid41859938,
year = {2026},
author = {Zhao, Y and Bazan, NG},
title = {Nutrition and gut-brain axis: opposing effects of dietary fiber and Western-style diets on Alzheimer's disease.},
journal = {Current opinion in clinical nutrition and metabolic care},
volume = {},
number = {},
pages = {},
doi = {10.1097/MCO.0000000000001223},
pmid = {41859938},
issn = {1473-6519},
abstract = {PURPOSE OF REVIEW: This review summarizes how diet shapes the gut-brain axis and contributes to Alzheimer's disease (AD) pathology, emphasizing the contrasting effects of Western-style diets and dietary fiber.

RECENT FINDINGS: Western diets rich in sugar and saturated fat disrupt gut microbial balance, increase intestinal permeability, and promote systemic inflammation, oxidative stress, and lipid metabolic imbalance, all of which accelerate neurodegeneration. In contrast, dietary fiber supports microbial diversity, improves lipid and glucose metabolism, and reduces neuroinflammation through both short-chain fatty acid (SCFA)-dependent and independent pathways involving bile acids, microbial lipids, and immune modulation. Recent animal and clinical data show that mixed-fiber supplementation can restore metabolic stability and cognitive function. In the 5xFAD mouse model (a transgenic AD model overexpressing five familial AD mutations), adding low-dose fiber to a high-sugar diet reshaped gut microbiota and improved AD-like pathology, identifying a reproducible set of fiber-sensitive bacterial taxa.

SUMMARY: Dietary patterns exert opposing effects on gut-brain communication. Nutrient excess drives dysbiosis and neuroinflammation, while dietary fiber promotes metabolic balance and neuronal resilience. Understanding these context-dependent microbial and metabolic interactions may guide precision dietary strategies for AD prevention and therapy.},
}

@article {pmid41860014,
year = {2026},
author = {Kim, D and Kondo, T and Imamura, K and Tsukita, K and Nagahashi, A and Sakasai, T and Inoue, H},
title = {Apolipoprotein E Deficiency Impairs Human Microglial Proliferation Accompanied by Elevated Cellular Oxidative Stress.},
journal = {Journal of cellular and molecular medicine},
volume = {30},
number = {6},
pages = {e71074},
doi = {10.1111/jcmm.71074},
pmid = {41860014},
issn = {1582-4934},
support = {JP23bm1323001//Japan Agency for Medical Research and Development/ ; JP24fm0208101//Japan Agency for Medical Research and Development/ ; JP23bm1423014//Japan Agency for Medical Research and Development/ ; JP23bm1223013//Japan Agency for Medical Research and Development/ ; JP23dk0207066//Japan Agency for Medical Research and Development/ ; JPMH24FC1008//Japan Agency for Medical Research and Development/ ; JP24bm1123047//Japan Agency for Medical Research and Development/ ; JP24wm0625201//Japan Agency for Medical Research and Development/ ; JP23bm1423012//Japan Agency for Medical Research and Development/ ; JP24wm0625501//Japan Agency for Medical Research and Development/ ; 20K16599//Japan Society for the Promotion of Science/ ; 23K06927//Japan Society for the Promotion of Science/ ; //Canon Foundation/ ; },
mesh = {*Microglia/metabolism/pathology ; Humans ; *Oxidative Stress/genetics ; *Apolipoproteins E/deficiency/genetics ; Cell Proliferation/genetics ; Alzheimer Disease/pathology/metabolism/genetics ; Reactive Oxygen Species/metabolism ; Induced Pluripotent Stem Cells/metabolism/pathology ; Inflammasomes/metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Transcriptome ; Lipid Droplets/metabolism ; },
abstract = {The APOE gene, which encodes Apolipoprotein E (ApoE), is the strongest genetic risk locus for Alzheimer's disease (AD). A substantial fraction of AD risk genes converges on pathways controlling lipid metabolism and immune regulation, in which microglia serve as a central integrative hub in the brain. Although microglial phenotypes linked to different APOE genotypes have been extensively characterised, the fundamental question of how ApoE shapes the core functions of human microglia remains unresolved. Here, we generated APOE knockout (KO) microglia from AD patient-derived induced pluripotent stem cells (iPSCs) and characterised their cellular and molecular phenotypes. Ablation of APOE resulted in marked lipid droplet accumulation and increased NLRP3 inflammasome activation. Transcriptomic analysis further revealed downregulation of cell cycle-related pathways, accompanied by enrichment of an oxidative stress-associated pathway. Consistent with these transcriptomic signatures, APOE KO microglia exhibited elevated intracellular reactive oxygen species (ROS) levels and a marked reduction in proliferative capacity. Given the importance of microglial proliferation for maintaining immune homeostasis in the brain, our findings highlight ApoE as being an important regulator of this process, with potential consequences for the pathogenesis of neurodegenerative disorders.},
}

*Microglia/metabolism/pathology
Humans
*Oxidative Stress/genetics
*Apolipoproteins E/deficiency/genetics
Cell Proliferation/genetics
Alzheimer Disease/pathology/metabolism/genetics
Reactive Oxygen Species/metabolism
Induced Pluripotent Stem Cells/metabolism/pathology
Inflammasomes/metabolism
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
Transcriptome
Lipid Droplets/metabolism

@article {pmid41860347,
year = {2026},
author = {Zhu, W and Li, H and Wang, K and Sun, M and Xiang, K and Shan, S and Ke, C},
title = {Evidence integration of acupuncture for prevention and treatment of Alzheimer's disease and mild cognitive impairment from a neuroimaging perspective.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261420235},
doi = {10.1177/13872877261420235},
pmid = {41860347},
issn = {1875-8908},
abstract = {BackgroundAcupuncture has clinical potential in treating Alzheimer's disease (AD) and mild cognitive impairment (MCI), but there is a lack of systematic review and presentation of clinical evidence from the perspective of neuroimaging in this field.ObjectiveTo conduct a systematic review of clinical studies on acupuncture for AD and MCI from the perspective of neuroimaging, and to comprehend the evidence distribution of relevant research.MethodsThis article retrieved all the neuroimaging clinical studies on acupuncture treatment for AD and MCI that were published and included in the seven databases from their establishment until February 22, 2025. It analyzed and organized the data based on the PICOS (Population, Intervention, Comparison, Outcome, Study design) principle, and presented the quality and distribution of evidence.ResultsA total of 58 studies were included. The diagnostic criteria for the research subjects mainly refer to the standards of Western medicine. The task design was mostly two-arm before-and-after comparisons and single-group immediate studies, with the intervention measures mainly including hand acupuncture and electroacupuncture. The study employed 8 neuroimaging techniques and 29 outcome measures, with a primary focus on brain functional activation regions and brain functional connectivity. Included studies had high bias risk in blinding design/implementation; overall evidence quality was acceptable.ConclusionsAcupuncture for AD and MCI demonstrates clear efficacy, which is supported by imaging evidence. In the future, more large-sample, multi-center joint clinical studies using neuroimaging methods will be needed to further investigate AD and MCI, providing more high-quality evidence-based medical evidence in this field.},
}

@article {pmid41860361,
year = {2026},
author = {Høilund-Carlsen, PF and Alavi, A and Costa, T and Neve, RL and Revheim, ME and Barrio, JR},
title = {Serious doubts about amyloid-β (Aβ) biomarkers and anti-Aβ immunotherapy.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261417548},
doi = {10.1177/13872877261417548},
pmid = {41860361},
issn = {1875-8908},
abstract = {Reports highlight new Alzheimer's disease treatments using anti-amyloid-β immunotherapy, but we see major concerns. The trials supporting lecanemab and donanemab approvals have methodological flaws, and the benefits may be smaller than the minimal clinically important difference-or absent-since patients with poor tolerance were excluded from efficacy analyses. Moreover, treatment increases amyloid-related imaging abnormalities, suggesting local tissue damage, and is linked to brain volume loss. These issues raise doubts about whether regulators are adequately balancing risks and benefits compared to academic critics.},
}

@article {pmid41860363,
year = {2026},
author = {Wei, X and Li, T and Yang, N and Xu, K and Ren, T and Cai, H and , and , and Yao, Z and Fu, Y and Hu, B},
title = {Distinct morphological patterns of the hippocampus and amygdala in normal and pathological aging.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261431845},
doi = {10.1177/13872877261431845},
pmid = {41860363},
issn = {1875-8908},
abstract = {BackgroundNormal aging is accompanied by cognitive decline and structural changes in the brain, most notably within the hippocampus and amygdala. However, distinguishing these age-related alterations from the earliest signs of neurodegenerative disorders remains challenging.ObjectiveThis study aims to investigate and compare the alteration patterns of hippocampus and amygdala during normal aging and in cases of mild cognitive impairment (MCI) and Alzheimer's disease (AD), which will provide insights into their distinct structural profiles.MethodsA total of 2195 participants aged 20-90 from three public cohorts (1364 cognitively normal controls, 623 MCI, and 208 AD) were grouped by decade to examine age- and disease-related differences in surface-based morphometry of hippocampus and amygdala. Radial distance, tensor-based morphometry, and multivariate tensor-based morphometry were calculated and combined to generate the Multivariate Morphometry Statistics, which capture both radial and tangential deformations at each vertex. Statistical and deformation analyses were further performed to identify the alteration patterns across 15000 surface vertices between age groups.ResultsIn healthy adults, significant intergroup differences were observed in the hippocampal CA1 and subiculum, as well as in the lateral, basolateral, and accessory basal nuclei of the amygdala. In MCI and AD, additional significant differences were detected in the hippocampal CA2-3 subfield and the central, medial, and cortical nuclei of the amygdala.ConclusionsWe provide a surface-based morphometry map of the hippocampus and amygdala across age groups in normal and pathological aging, revealing distinct morphological patterns that enhance understanding of aging and neurodegeneration.},
}

@article {pmid41860371,
year = {2026},
author = {Jian, JM and Li, XP and Xie, JH and Hu, JN and Liang, J and Zhu, L and Zhao, HD and Zeng, F and Jin, WS and Fan, DY and Sun, HL},
title = {Chronic high-altitude hypoxia exacerbates cognitive impairment and Alzheimer's disease pathology.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261431844},
doi = {10.1177/13872877261431844},
pmid = {41860371},
issn = {1875-8908},
abstract = {BackgroundChronic hypoxia has been acknowledged as a significant risk factor for Alzheimer's disease (AD), yet the impact of high-altitude hypoxia on AD pathogenesis remains poorly understood.ObjectiveThis study aims to investigate the effects of chronic high-altitude hypoxia on cognitive function and AD-related pathology.MethodsA cross-sectional cohort comprising 186 high-altitude migrants (HAM) and 378 high-altitude natives (HAN) was recruited for a preliminary assessment. We further conducted 101 HAM, 135 HAN, and 66 low-altitude controls (LA) for plasma biomarkers research. Plasma Aβ40, Aβ42, and T-tau levels were quantified by SIMOA. In parallel, APP/PS1 mice were exposed to hypobaric hypoxia (simulated at 5,500 m) or normoxia for 30 days, followed by behavioral tests, brain immunohistochemistry, and transcriptomic/proteomic analyses.ResultsHAM subjects exhibited significant deficits in Montreal Cognitive Assessment scores and delayed recall subscores compared to LA controls, with both measures showing a positive correlation with peripheral oxygen saturation (SpO2). Notably, HAN showed preserved memory despite lower overall cognitive scores. Plasma levels of amyloid-β (Aβ)40, Aβ42, and Aβ42/Aβ40 ratio were significantly lower in both HAM and HAN groups compared to the LA group. In mice, chronic hypoxia exacerbated hippocampal Aβ deposition and induced spatial memory decline. Multi-omics analyses revealed the upregulation of oxidative stress and neuroinflammatory pathways and identified S100A8/A9 as a potential key mediator in hypoxia-accelerated AD pathology.ConclusionsOur findings demonstrate that chronic high-altitude hypoxia contributes to cognitive decline and AD-related pathological changes, likely mediated by Aβ burden and oxidative stress. High-altitude hypoxia might be an important environmental risk factor for AD.},
}

@article {pmid41860372,
year = {2026},
author = {Damodarasamy, M and Hernandez, GJ and Johnson, RS and Keene, CD and Latimer, CS and MacCoss, MJ and Banks, WA and Erickson, MA and Reed, MJ},
title = {Lecanemab alters basement membrane collagen IV in viable microvessels isolated from brains with high Alzheimer's disease neuropathology.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261433167},
doi = {10.1177/13872877261433167},
pmid = {41860372},
issn = {1875-8908},
abstract = {Amyloid-β (Aβ) can deposit in or near the microvascular basement membrane (BM) in Alzheimer's disease (AD). We examined the effect of the Aβ binding antibody, lecanemab, on BM collagen IV (Col-IV) using viable brain microvessels (MV) isolated from human postmortem brain tissue with high AD neuropathologic change (ADNC=3, 16 females (mean 86 years), 11 males (mean 81 years)). MVs were exposed to lecanemab or isotype for 4 days and examined for Col-IV related outcomes: western blotting, capillary electrophoresis, RT-PCR, and degraded Col-IV. We find a subset of MV from some donors demonstrate Col-IV changes that could cause microvascular injury when exposed to lecanemab.},
}

@article {pmid41860528,
year = {2026},
author = {Rubin, R},
title = {Lithium for Alzheimer Disease-Pilot Study Sets the Stage for Larger Trials.},
journal = {JAMA},
volume = {},
number = {},
pages = {},
doi = {10.1001/jama.2026.3046},
pmid = {41860528},
issn = {1538-3598},
}

@article {pmid41860664,
year = {2026},
author = {Qian, G and Zou, J and Huang, Q and Gao, M and Sun, Y and Wu, X and Gu, L and Qian, Y and Wu, X},
title = {Polygala Tenuifolia Willd. Ameliorates Neuronal Damage in Alzheimer's Disease Model Mice by Regulating Ferroptosis Through Modulation of the Nrf2/SLC7A11/GPX4 Axis.},
journal = {Applied biochemistry and biotechnology},
volume = {},
number = {},
pages = {},
pmid = {41860664},
issn = {1559-0291},
support = {No.SKY2021019//Suzhou Science and Technology Bureau Science and Technology Development Plan Project/ ; No.CSWS202120//Changshu Municipal Health Commission Science and Technology Plan Project/ ; No.CSWS202221//Changshu Municipal Health Commission Science and Technology Development Plan Project/ ; },
}

@article {pmid41860762,
year = {2026},
author = {Miller-Winder, AP and Relerford, RR and Schierer, A and Murawski, A and Olvera, C and Curtis, LM and Kim, KY and Ramirez-Zohfeld, V and Lindquist, LA},
title = {Phenotypes of Older Adults Planning for Alzheimer's Disease Support.},
journal = {Journal of the American Geriatrics Society},
volume = {},
number = {},
pages = {},
doi = {10.1111/jgs.70401},
pmid = {41860762},
issn = {1532-5415},
support = {P30AG059988/AG/NIA NIH HHS/United States ; R01AG058777/AG/NIA NIH HHS/United States ; R01AG068421/AG/NIA NIH HHS/United States ; R01AG083034/AG/NIA NIH HHS/United States ; R01AG30611/AG/NIA NIH HHS/United States ; },
}

@article {pmid41860868,
year = {2026},
author = {Trautwig, AN and Shantaraman, A and Chung, M and Dammer, EB and Ping, L and Duong, DM and Watson, CM and Petrucelli, L and Ward, ME and Glass, JD and Nelson, PT and Levey, AI and McEachin, ZT and Seyfried, NT},
title = {Subtyping based on hippocampal cryptic exon burden reveals proteome-wide changes associated with TDP-43 and Alzheimer's disease pathology.},
journal = {Cell reports},
volume = {45},
number = {4},
pages = {117142},
doi = {10.1016/j.celrep.2026.117142},
pmid = {41860868},
issn = {2211-1247},
abstract = {TDP-43 pathology defines limbic-predominant age-related TDP-43 encephalopathy (LATE-NC) and frequently co-occurs with Alzheimer's disease neuropathologic change (ADNC), yet the molecular consequences of overlapping pathology remain unclear. We performed biochemical and proteomic analyses of postmortem hippocampal tissue from 90 individuals spanning control, LATE-NC, ADNC, and ADNC+LATE-NC groups. Cryptic exon (CE) inclusion was quantified across eight TDP-43-regulated transcripts and related to phosphorylated TDP-43 (pTDP-43), amyloid, and tau pathology. ADNC+LATE-NC cases showed the highest CE levels. Although CE inclusion correlated with pTDP-43, CE measures were more strongly intercorrelated and defined low, intermediate, and high CE subtypes largely independent of amyloid and tau. Proteome-wide analyses revealed reduced abundance of CE-target proteins and disruption of synaptic, endosomal, and RNA-binding pathways in high CE cases. These signatures overlapped with changes in TDP-43-depleted human i[3]Neurons, supporting biological relevance. Overall, CE burden provides a robust molecular classifier of TDP-43 dysfunction across LATE-NC and ADNC.},
}

@article {pmid41860953,
year = {2026},
author = {Wu, Y and Xu, L and Aung, YW and Daoud, AM},
title = {Prior-guided factorization for reliable imputation of scRNA-seq data.},
journal = {PLoS computational biology},
volume = {22},
number = {3},
pages = {e1014051},
doi = {10.1371/journal.pcbi.1014051},
pmid = {41860953},
issn = {1553-7358},
mesh = {Animals ; *Single-Cell Analysis/methods/statistics & numerical data ; Mice ; Computational Biology/methods ; *RNA-Seq/methods/statistics & numerical data ; *Sequence Analysis, RNA/methods ; Alzheimer Disease/genetics ; Algorithms ; Humans ; Gene Expression Profiling/methods ; Single-Cell Gene Expression Analysis ; },
abstract = {Single-cell RNA sequencing (scRNA-seq) provides an important means to reveal the heterogeneity and dynamic processes of tissues, organisms, and complex diseases, but technical capture loss (dropout) often obscures true biological expression, and existing imputation methods have difficulty distinguishing biological zeros (silent expression) from technical noise. To address this, we propose the imputation framework scZN. scZN assumes that the observed scRNA-seq data arise from a combination of RNA's two-state transcription process and dropout, and formulates imputation as nonnegative factorization: decomposing the raw count matrix into two interpretable nonnegative factors, performing learning and optimization under constraints from prior knowledge and multiple regularizations, thereby reconstructing the cellular expression landscape. Experiments show that scZN can capture the true distributional characteristics at both the gene and cell levels and significantly suppress spurious activation of genes that should not be expressed. Across multiple real datasets, it outperforms dozens of state-of-the-art methods. Especially in complex experimental design scenarios, scZN markedly improves trajectory inference for embryonic stem cells and mouse dentate gyrus data. In Alzheimer's disease data, scZN can also effectively recover pathways related to neuroinflammation, improving downstream scRNA-seq analysis. Overall, scZN provides a unified framework for missing-value imputation and expression reconstruction that combines accuracy and interpretability.},
}

Animals
*Single-Cell Analysis/methods/statistics & numerical data
Mice
Computational Biology/methods
*RNA-Seq/methods/statistics & numerical data
*Sequence Analysis, RNA/methods
Alzheimer Disease/genetics
Algorithms
Humans
Gene Expression Profiling/methods
Single-Cell Gene Expression Analysis

@article {pmid41861051,
year = {2026},
author = {Ouyang, L and Shan, X and Sun, X and Peng, J and Ye, H and Wen, Y and Xiao, F and Zhu, H and Zhang, Z and Guo, H and Kuang, W},
title = {The Global Macroeconomic Burden of Neurological Disorders.},
journal = {Neuroepidemiology},
volume = {},
number = {},
pages = {1-21},
doi = {10.1159/000551382},
pmid = {41861051},
issn = {1423-0208},
abstract = {BACKGROUND: Existing studies have focused on neurological disorders' morbidity and mortality, yet their economic consequences remain unquantified. We estimated the macroeconomic impact of neurological disorders and subcategories at the global, super-regional, and national levels in 2019 and 2021, and described sex and age distribution.

METHODS: We obtained mortality and morbidity data, reflecting long-run and short-run disease burden respectively, from the Institute of Health Metrics and Evaluation (IHME) Global Burden of Disease 2021 study. Purchasing power parity (PPP)-adjusted gross domestic product (GDP) data were sourced from the World Bank. Economic burden was estimated using the value of lost welfare (VLW) framework, which rests on the value of a statistical life (VSL) and covers non-market losses. All monetary values are expressed in 2021 international dollars adjusted for PPP.

RESULTS: In 2021, the global VLW of neurological disorders was $10,710.51 billion, equal to 7.23% of global gross domestic product (GDP), and the short-run economic burden predominates over the long-run component. By subcategories, headache disorders accounted for 44.7%, and Alzheimer's disease and other dementias for 35.7%. From 2019 to 2021, global VLW changed little, while VLW/GDP (%) declined slightly due to rising nominal GDP.

CONCLUSIONS: Neurological disorders impose substantial economic burden globally, particularly in High-income super-region and older populations. Policy emphasis should reflect regional burden profiles. High-income settings prioritize earlier dementia detection, life-course risk-factor control, and caregiver support., while low- and middle-income settings scale primary-care chronic management and effective acute headache therapies.},
}

@article {pmid41861098,
year = {2026},
author = {Jayanti, S and Vítek, L and Gazzin, S and Tiribelli, C},
title = {Bilirubin as a Modulator of WNK1 Protein Signaling: Implications for Neuroinflammatory Diseases.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e20531},
doi = {10.1002/advs.202520531},
pmid = {41861098},
issn = {2198-3844},
support = {MH CZ-DRO-VFN64165//Czech Ministry of Health/ ; LUAUS26259//Czech Ministry of Health and the Inter-Action project/ ; },
abstract = {Previously regarded merely as a potentially harmful waste product of heme catabolism, bilirubin has now emerged as a pleiotropic molecule with potent antioxidant, anti-inflammatory, and hormone-like properties. Recent findings have revealed protective effects against cardiovascular, metabolic, autoimmune, and neoplastic diseases, as well as neurological disorders. The growing understanding of neuroinflammatory processes has opened new avenues for exploring the role of bilirubin in neuroprotection. Despite the increasing number of studies investigating the protective effects of bilirubin in neurological diseases, the molecular mechanisms underlying its anti-inflammatory actions in the brain remain insufficiently understood. In this perspective article, With-No-Lysine (K) kinase 1 (WNK1) is discussed as a newly identified molecular target of bilirubin, highlighting its potential implications for neuroinflammatory diseases. The bilirubin-WNK1 axis may represent a previously unrecognized protective mechanism that could be leveraged to mitigate inflammation-driven neurodegeneration. This interaction can open new therapeutic opportunities for neurodegenerative disorders such as multiple sclerosis (MS), Alzheimer's disease, and Parkinson's disease.},
}

@article {pmid41861196,
year = {2026},
author = {Zhang, HX and Li, HY},
title = {Mitochondrial dysfunction and programmed cell death in Alzheimer's disease: A retrospective bioinformatics study.},
journal = {Medicine},
volume = {105},
number = {12},
pages = {e48105},
doi = {10.1097/MD.0000000000048105},
pmid = {41861196},
issn = {1536-5964},
support = {NA//Tianchi Talent Program/ ; },
mesh = {Humans ; *Alzheimer Disease/genetics/physiopathology ; Computational Biology/methods ; Retrospective Studies ; *Mitochondria/genetics/metabolism ; *Apoptosis/genetics ; Superoxide Dismutase-1/genetics ; Mitochondrial Precursor Protein Import Complex Proteins ; Membrane Transport Proteins/genetics ; Gene Expression Profiling ; Machine Learning ; },
abstract = {Alzheimer's disease (AD) is a major cause of dementia, and this paper explores the unclear roles of mitochondrial dysfunction and programmed cell death in AD. Differentially expressed genes (DEGs) were identified using AD datasets GSE63061 and GSE63060 from the Gene Expression Omnibus. DEGs were intersected with mitochondria-related genes and programmed cell death-related genes to obtain DEGs (in AD) intersected with mitochondrial-related genes and DEGs (in AD) intersected with programmed cell death-related genes. Correlation analysis of these DEGs was used to identify candidate genes. Machine learning algorithms were applied to key genes, followed by functional enrichment, network construction, immune infiltration analysis, drug prediction, and expression validation. Two key genes, superoxide dismutase 1 (SOD1) and translocase of the outer mitochondrial membrane 7 (TOMM7), were identified and linked to pathways like ribosome and chemokine signaling. A strong positive correlation (0.76, P < .001) was found between them. Immune analysis showed differences in 11 immune cells between AD and controls, with TOMM7 positively linked to activated CD8 T cells and negatively to myeloid-derived suppressor cells. SOD1 and TOMM7 are regulated by 4 miRNAs and 71 long noncoding RNAs (lncRNAs). Seventeen potential AD drugs, including urea and nitric oxide, were predicted. Two key genes, SOD1 and TOMM7, related to mitochondria and PCD, were identified as potential targets for understanding AD's etiology, detection, and therapeutic approaches.},
}

Humans
*Alzheimer Disease/genetics/physiopathology
Computational Biology/methods
Retrospective Studies
*Mitochondria/genetics/metabolism
*Apoptosis/genetics
Superoxide Dismutase-1/genetics
Mitochondrial Precursor Protein Import Complex Proteins
Membrane Transport Proteins/genetics
Gene Expression Profiling
Machine Learning

@article {pmid41861574,
year = {2026},
author = {Denev, R and Berkov, S},
title = {A fast and simple method for GC-MS quantification of galanthamine in Hippeastrum papilio (Ravena) Van Sheepen and assessment of its alkaloid fractions.},
journal = {Journal of chromatography. A},
volume = {1774},
number = {},
pages = {466902},
doi = {10.1016/j.chroma.2026.466902},
pmid = {41861574},
issn = {1873-3778},
abstract = {BACKGROUND: Galanthamine, an AChE inhibitor marketed for symptomatic treatment of mild to moderate Alzheimer's disease, is produced by both chemical synthesis and extraction from plant of the Amaryllidoideae subfamily. There are a few validated GC-MS and HPLC-MS methods for its quantification in plant material. All of these methods apply multi-step sample preparation procedures including toxic solvents. The assessment of plant material and development of extraction methodologies from new plant sources (e.g. Hippeastrum papilio) requires validation of quantitative analytical methods considering the species alkaloid pattern.

RESULTS: The extraction of galanthamine from H. papilio raw material was optimized selecting 0.072% of HCl water solution as the most effective extractant. An aliquot (1 µL) of the total extract (1 mL) was directly injected into the GC-MS system avoiding any purification steps with toxic solvents. Selectivity, linearity, sensitivity, precision, accuracy, stability and robustness were determined. The LLOQ and LLOD in SIM mode were found at a concentration of 10 ng/mL and 2 ng/mL, respectively. The method was used for assessment of plant raw material, alkaloid fractions and extraction effectiveness.

SIGNIFICANCE: The method describes the fastest and simplest extraction procedure and direct aqueous injection into the GC-MS for quantification of galanthamine in plant material. As compared to the LC-MS, the use of EIMS detector provides important information and advantage in the assessment of alkaloid fractions from new plant sources of galanthamine.},
}

@article {pmid41861772,
year = {2026},
author = {Liu, P and Liu, J and Wang, J and Du, Y and Liu, Z and Zhang, H and Zhu, A and Zhang, G and Meng, X and Zhao, C and Zhang, W and Dang, L and Zhang, W and Qu, Q and Qu, Y},
title = {Characteristics of infusion-related reactions to lecanemab in early Alzheimer's disease: A multicenter real-world study in Northwestern China.},
journal = {The journal of prevention of Alzheimer's disease},
volume = {13},
number = {5},
pages = {100542},
doi = {10.1016/j.tjpad.2026.100542},
pmid = {41861772},
issn = {2426-0266},
abstract = {BACKGROUND: Infusion-related reactions (IRRs) represent the most common adverse events associated with lecanemab. However, real-world data on IRR characteristics and risk factors in Asian populations, particularly Chinese, remain scarce.

METHODS: In a multicenter prospective registry, 139 patients with early Alzheimer's disease (AD) receiving lecanemab were included. IRRs were physician-confirmed. Multivariable logistic regression identified independent predictors.

RESULTS: The cumulative IRR incidence was 12.36 %, highest at the first infusion (17.3 %) and decreased significantly thereafter (P < 0.001). Fever (54.2 %) and dizziness (16.7 %) were the most common symptoms. 45.8 % of IRRs occurred 2-24 hours after infusion. All IRRs were mild (Grade 1) and self-limited. Hypertension (OR = 5.017, P = 0.007) and higher Fazekas score (OR = 2.734, P = 0.017) were independently associated with IRR.

DISCUSSION: In this Chinese real‑world cohort, lecanemab‑associated IRRs were less frequent, mild, and delayed. Hypertension and white‑matter hyperintensity severity emerged as key risk factors, underscoring the potential role of cerebrovascular health in IRR susceptibility.},
}

@article {pmid41861779,
year = {2026},
author = {Hernández, D and Schlicht, SM and Clarke, JE and Daniszewski, M and Karch, CM and , and Goate, AM and Pébay, A},
title = {Retraction notice to "Generation of a gene-corrected human isogenic iPSC line from an Alzheimer's disease iPSC line carrying the PSEN1 H163R mutation" [Stem Cell Res. 79 (2024) 103495].},
journal = {Stem cell research},
volume = {93},
number = {},
pages = {103956},
doi = {10.1016/j.scr.2026.103956},
pmid = {41861779},
issn = {1876-7753},
}

@article {pmid41861831,
year = {2026},
author = {Taravella Oill, AM and Plaisier, SB and Phung, TN and Wilson, MA},
title = {Best practices for improving alignment and variant calling on human sex chromosomes.},
journal = {American journal of human genetics},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajhg.2026.02.019},
pmid = {41861831},
issn = {1537-6605},
abstract = {Sex chromosome complement is the largest karyotypic variation observed in humans. X and Y chromosomes were once a pair of homologous autosomes. Although chromosome X and Y differentiated from one another, they still share high sequence similarity in some regions, such as the pseudoautosomal regions (PARs) and X-transposed region (XTR). The sex chromosomes violate some assumptions of autosomes but are not always processed separately in genomics. We undertook a simulation study to assess the effects of standard autosomal versus sex chromosome complement (SCC)-informed alignment, variant calling, and filtering strategies on variants detected on the sex chromosomes. We find that aligning samples to a reference genome informed by the SCC of the sample increases the number of true positives called in the PARs, and, in XX samples only, also the XTR. In contrast, in XY samples, masking the XTR during alignment results in a 10-fold higher rate of false positives (FPs). We further find that haploid calling on the sex chromosomes in XY samples reduces the number of FPs compared to diploid calling but does not decrease the number of false negatives. Improving the accuracy of variant calling results in detection of variants that could be relevant to studies of health and disease, including variants we recovered in genes implicated in cardiomyopathy, immunodeficiency, and Alzheimer disease. We recommend future genomic analyses implement the following best practices for detecting variants: aligning samples to versions of the human reference genome informed by the SCC of the sample and using accurate ploidy when calling variants.},
}

@article {pmid41861975,
year = {2026},
author = {Huang, S and Lai, W and Zhao, Y and Pan, K and Xu, H and Lin, S and Liao, M and Liu, X and Lu, P and Wu, Y and Yang, W and Song, P and He, H and Hu, Y and Li, C},
title = {Hypertension, Antihypertensive Treatment, and Memory Decline: Consistent and Divergent Patterns in Aging Populations across Four Countries, 2010-2019.},
journal = {American journal of preventive medicine},
volume = {},
number = {},
pages = {108343},
doi = {10.1016/j.amepre.2026.108343},
pmid = {41861975},
issn = {1873-2607},
abstract = {INTRODUCTION: Memory decline is a hallmark of all-cause dementia. Hypertension, a highly prevalent and modifiable risk factor, is a critical intervention target. Cross-national, long-term studies examining the relationship between hypertension management and 10-year memory decline remain limited.

METHODS: We analyzed 2010-2019 data from four nationally representative aging cohorts. Hypertension (BP ≥140/90 mmHg or antihypertensive medications use) was categorized as treated and untreated. Memory was assessed using immediate and delayed word recall tasks. Linear mixed-effects models evaluated memory trajectories by hypertension and treatment status. Pooled analyses examined cross-country differences. Data analysis occurred from December 2024-January 2026.

RESULTS: Compared with non-hypertensive participants, hypertensive participants had a faster annual decline in the US (-0.010; 95% CI: -0.015, -0.006) and England (-0.011; 95% CI: -0.018, -0.004). Compared with treated hypertensive participants, untreated hypertensive participants had a slower annual decline among hypertensive participants in the US (0.010; 95% CI: 0.003, 0.017), but a faster decline in China (-0.022; 95% CI: -0.034, -0.011). Pooled analyses showed no cross-country differences in the association between hypertension and memory; however, compared with treated hypertension in the US, untreated hypertension was associated with faster memory decline in Mexico (-0.028; 95% CI: -0.051, -0.006) and China (-0.032; 95% CI: -0.045, -0.020).

CONCLUSIONS: Hypertension and treatment status are associated with memory decline in country-specific patterns. These findings highlight hypertension as a key modifiable risk factor and support prevention and treatment to promote cognitive health. Tailored approaches that align with local healthcare systems and population needs are essential.},
}

@article {pmid41862118,
year = {2026},
author = {Chen, W and Huang, N and Huang, W and Wang, M and Luo, Y and Huang, J},
title = {TREM2 as a possible link between Alzheimer's disease and diabetes mellitus.},
journal = {Experimental neurology},
volume = {},
number = {},
pages = {115739},
doi = {10.1016/j.expneurol.2026.115739},
pmid = {41862118},
issn = {1090-2430},
abstract = {Alzheimer's disease (AD) and diabetes mellitus (DM) represent escalating global health burdens, with epidemiological and clinical studies demonstrating a strong association between them. Diabetic patients face a significantly increased risk of AD, and poor glycemic control can accelerate AD progression. Chronic low-grade inflammation is increasingly recognized as a central mechanism bridging the two diseases. Triggering receptor expressed on myeloid cells 2 (TREM2), a key immune regulator, has emerged as a critical player in both AD and DM. In AD, TREM2 is specifically expressed on microglia, mediating neuroinflammatory and neurodegenerative processes while regulating both amyloid-β (Aβ) and Tau pathology. In DM, TREM2 contributes to insulin resistance and metabolic dysregulation. Genetic variants of TREM2 are established risk factors for AD, while altered TREM2 expression correlates with DM pathology. This review summarizes TREM2's structural and functional characteristics, its dual roles in AD and DM, and its potential as a therapeutic target. Elucidating these shared TREM2-mediated mechanisms may provide novel insights into the pathological interplay between AD and DM and inform precision therapeutic strategies.},
}

@article {pmid41862120,
year = {2026},
author = {Xue, C and Chen, C and Zou, X and Li, S and Lv, Y and Liu, W},
title = {Hippocampal astrocyte St6galnac5 silencing improves spatial memory and preserves synaptic integrity in an AD mouse model.},
journal = {Experimental neurology},
volume = {},
number = {},
pages = {115742},
doi = {10.1016/j.expneurol.2026.115742},
pmid = {41862120},
issn = {1090-2430},
abstract = {Cognitive resilience in Alzheimer's disease (AD) requires the maintenance of synaptic integrity despite progressive pathological insults. Reactive astrocytes can switch between neuroprotective and neurotoxic states, and their maladaptive transition significantly accelerates neurodegeneration, yet the molecular drivers of this shift remain elusive. Here, using published single-nucleus transcriptomic data, we identified the sialyltransferase St6galnac5 as a candidate regulator associated with reactive, pro-inflammatory astrocyte states. We further show that astrocyte-specific, AAV-mediated knockdown of St6galnac5 in female 3xTg-AD mice improves spatial learning, memory and anxiety-like behaviors. Neuropathological assessment revealed that this functional recovery was underpinned by a marked reduction in amyloid-β and tau pathologies, alongside the preservation of synaptic integrity. Consistent with a shift toward a less inflammatory astrocyte state, St6galnac5 knockdown decreased A1-associated markers and increased A2-associated markers in vitro and alleviated neurite outgrowth deficits in neuron-astrocyte co-culture. Together, our findings identify St6galnac5 as a critical molecular switch driving astrocytic dysfunction in AD, and further propose that targeted inhibition of this sialylation pathway represents a viable strategy to bolster astrocytic resilience and slow disease progression.},
}

@article {pmid41862124,
year = {2026},
author = {Asante, J and Barger, SW},
title = {Impact of P-glycoprotein substrates on transendothelial transport of amyloid-β peptide in an in vitro model.},
journal = {Neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neuroscience.2026.03.020},
pmid = {41862124},
issn = {1873-7544},
abstract = {Alzheimer's disease (AD) is a pervasive neurodegenerative disorder and the leading cause of dementia, strongly associated with amyloid β-peptide (Aβ) accumulation in the cerebrum. In most cases, this aggregation is primarily due to inefficiencies in the degradation and clearance of Aβ, notably its transport across the blood-brain barrier (BBB) into the bloodstream. This study investigates the role of P-glycoprotein (P-gp), a key transporter in transporting Aβ across endothelial-cell monolayers, focusing on the effects of other P-gp substrates on this process. In vitro models of the endothelial vessel wall were tested in monoculture and non-contact coculture techniques, optimizing conditions to enhance barrier integrity, as assessed by transendothelial electrical resistance (TEER) and dextran leakage assays. The hCMEC/D3 cell line was compared to primary human brain microvascular endothelial cells (HBMEC); the latter exhibited greater barrier integrity. Conditions of cell density and days in culture were optimized. The transport of fluorescently labeled Aβ1-40 was tested in the presence of P-gp substrates digoxin, lansoprazole, atorvastatin, and mirabegron. Atorvastatin, digoxin, and lansoprazole significantly increased Aβ efflux, while mirabegron inhibited it, effects qualitatively consistent with the risk for AD associated with their administration to human patients. These findings demonstrate the potential of P-gp substrates to differentially impact Aβ transport, providing therapeutic implications for AD.},
}

@article {pmid41862174,
year = {2026},
author = {Iacobucci, G},
title = {Alzheimer's drugs: Lecanemab and donanemab to be reconsidered for NHS after appeal.},
journal = {BMJ (Clinical research ed.)},
volume = {392},
number = {},
pages = {s551},
doi = {10.1136/bmj.s551},
pmid = {41862174},
issn = {1756-1833},
}

@article {pmid41668173,
year = {2026},
author = {Lu, H and Zhang, Y and Chen, C and Xie, H and Li, Y and Qiu, S},
title = {Capillary-Associated Microglia in Neurovascular Coupling: Localization, Mechanisms, and Disease Implications.},
journal = {Journal of neuroinflammation},
volume = {23},
number = {1},
pages = {},
pmid = {41668173},
issn = {1742-2094},
support = {2022GZ63//Huzhou Municipal Public Welfare Application Research Project/ ; },
abstract = {Capillary-Associated Microglia (CAMs) are increasingly recognized as integral components of the neurovascular unit (NVU) that interface with intracerebral capillaries and are implicated in microcirculatory regulation, neurovascular coupling (NVC), and blood–brain barrier (BBB) maintenance. Rather than a rigid lineage-defined subset, CAMs are often best conceptualized as an anatomically anchored and context-responsive microglial state in which somata and/or primary processes closely appose the capillary wall, enabling continuous sensing of vascular-derived signals and local modulation of vascular function. Advances in in vivo two-photon imaging, single-cell and spatial transcriptomics, and genetic perturbation approaches have begun to delineate their positioning dynamics and candidate molecular programs. Mechanistically, CAMs can engage purinergic signaling—most prominently via the PANX1–P2Y12R axis—to detect extracellular nucleotides and support process responses and capillary association, while additional pathways involving COX-1–dependent prostanoid production and CD39-mediated nucleotide hydrolysis may contribute to basal tone regulation and activity-dependent vascular reactivity, in part through local adenosine availability. Through coordinated interactions with endothelial cells, pericytes, astrocytes, and neurons, CAMs occupy a strategic immunovascular interface, where they may couple immune surveillance to BBB integrity and metabolic homeostasis. In disease, alterations in the positioning and signaling of CAMs have been linked to a range of neurological and neurovascular disorders, including Alzheimer’s and Parkinson’s diseases, cerebral small vessel disease, diabetic encephalopathy, and ischemic stroke, with emerging evidence suggesting that chronic inflammatory or metabolic stress can reshape these programs and compromise NVC. Key challenges remain in establishing operational definitions and cross-species comparability, achieving long-term in vivo tracking with causal resolution, and improving the physiological fidelity of in vitro models. Future work will benefit from standardized criteria for CAMs identification, longitudinal multimodal imaging integrated with spatial omics, refined microphysiological platforms, and targeted modulation or delivery strategies, with the aim of translating mechanistic insights into reliable biomarkers and therapeutic opportunities for neuroinflammatory and neurovascular pathologies.},
}

@article {pmid41673700,
year = {2026},
author = {Goulding, DS and Williams, HC and Gorman, AA and Devanney, NA and Harrison, DA and Walsh, AE and Tuck, T and Zajac, DJ and Macauley, SL and Estus, S and Tcw, J and A Johnson, L and Morganti, JM},
title = {APOE4 drives maladaptive heterogeneity and immunometabolic responses of astrocytes.},
journal = {Journal of neuroinflammation},
volume = {23},
number = {1},
pages = {},
pmid = {41673700},
issn = {1742-2094},
support = {R01 AG068330/AG/NIA NIH HHS/United States ; R01 AG093847/AG/NIA NIH HHS/United States ; RF1NS118558/NS/NINDS NIH HHS/United States ; RF1NS118558/NS/NINDS NIH HHS/United States ; },
abstract = {UNLABELLED: Apolipoprotein E4 (APOE4) is the strongest risk allele associated with the development of late onset Alzheimer’s disease (AD). Across the CNS, astrocytes are the predominant expressor of APOE while also being critical mediators of neuroinflammation and cerebral metabolism. APOE4 has been consistently linked with dysfunctional inflammation and metabolic processes, yet insights into the molecular constituents driving these responses remain unclear. Utilizing complementary approaches across humanized APOE mice and isogenic human iPSC astrocytes, we demonstrate that ApoE4 alters the astrocyte immunometabolic response to pro-inflammatory stimuli. Our findings show that ApoE4-expressing astrocytes acquire distinct transcriptional repertoires at single-cell and spatially-resolved domains, which are driven in-part by preferential utilization of the cRel transcription factor. Further, inhibiting cRel translocation in ApoE4 astrocytes abrogates inflammatory-induced glycolytic shifts and in tandem mitigates production of multiple pro-inflammatory cytokines. Altogether, our findings elucidate novel cellular underpinnings by which ApoE4 drives maladaptive immunometabolic responses of astrocytes.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-026-03698-2.},
}

@article {pmid41680800,
year = {2026},
author = {Wu, C and Gao, LY and Sun, W and Zhao, BK and Ma, YH and Song, HQ and , },
title = {Plasma lipidomic profiling reveals the potential protective role of lipids in cerebral small vessel disease.},
journal = {Lipids in health and disease},
volume = {25},
number = {1},
pages = {},
pmid = {41680800},
issn = {1476-511X},
support = {82401662//National Natural Science Foundation of China/ ; tsqn202312391//Taishan Scholar Project of Shandong Province/ ; },
abstract = {BACKGROUND: Limited understanding of the pathophysiology of cerebral small vessel disease (CSVD) has hampered the development of effective treatments. Lipidomics offers a promising approach for identifying molecular signatures, clarifying underlying pathogenic mechanisms, and predicting disease severity and progression.

METHODS: A total of 1161 participants with lipidomic data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database were included and matched to each neuroimaging marker of CSVD separately, including cerebral microbleeds (CMBs, n = 578), white matter hyperintensities (WMHs, n = 650), lacunes (n = 1125), and CSVD burden (n = 546). Three complementary classification strategies (class-based grouping, model-based clustering, and individual lipid species) were employed to investigate lipid signatures across various CSVD markers. A multimodel regression framework followed by a series of sensitivity analyses was used to further identify lipid species showing robust associations with each CSVD marker.

RESULTS: A total of 46 lipid classes, 25 lipid clusters, and 749 lipid species were quantified. Individuals with CSVD presented broadly reduced plasma lipid levels, particularly those of glycerophospholipids and glycerolipids. A multimodel regression framework initially screened 32 lipid species associated with the presence or progression of CSVD. Subsequent sensitivity analyses narrowed these to 13 robust species, including phosphatidylcholine, triacylglycerol, phosphatidylethanolamine, alkenyl-phosphatidylethanolamine, and sphingomyelin. Among these, elevated levels of PC(36:4)[+ OH] and TG(56:6)[NL-20:4] were associated with lower odds of CMBs and reduced WMH volumes, respectively, whereas higher levels of PC(15:0_20:3) and SM(d16:1/19:0) were linked to lower odds of lacunes, with all associations consistently observed across baseline, year 1, and year 2.

CONCLUSION: This study revealed dysregulated lipid metabolism across distinct magnetic resonance imaging phenotypes of CSVD and revealed multiple lipid species that are consistently associated with the presence and progression of these phenotypes, underscoring the potential of lipidomics for the earlier identification and prevention of CSVD and informing future diagnostic development and mechanistic studies.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12944-026-02891-9.},
}

@article {pmid41691355,
year = {2026},
author = {Chen, X and Yu, W and Zhu, Z},
title = {Postoperative neurocognitive disorder: migration and crosstalk of inflammation in the peripheral and central nervous system.},
journal = {Perioperative medicine (London, England)},
volume = {15},
number = {1},
pages = {},
pmid = {41691355},
issn = {2047-0525},
abstract = {Postoperative neurocognitive disorder (PNCD) causeschallenges in addition to that resulting from surgery. These adverse effects not only impact patients in the short term but can also lead to long-term consequences, including an increased mortality rate, a higher risk of developing Alzheimer’s disease, and a decline in post-surgical quality of life and longevity. To better prevent and treat PNCD and improve the prognosis of surgical patients, it is essential to enhance the understanding of the pathogenesis of PNCD. According to recent studies, peripheral inflammation and neuroinflammation may collectively contribute to the development of PNCD. This article discusses the sources of peripheral inflammation, the migration and crosstalk of inflammation between the periphery and the central nervous system, and whether this crosstalk could provide new insights into preventing and treating PNCD.},
}

@article {pmid41843184,
year = {2026},
author = {Fenton, L and Weissberger, GH and Salminen, LE and Samek, A and Noriega-Makarskyy, DT and Molinare, CP and Williams, J and Oyen, E and Kim, P and Axelrod, J and Mosqueda, L and Yassine, H and Han, SD},
title = {Brain macrostructure correlates of financial altruism in older adults without dementia.},
journal = {Brain imaging and behavior},
volume = {20},
number = {2},
pages = {},
pmid = {41843184},
issn = {1931-7565},
abstract = {UNLABELLED: Greater financial altruism (i.e., the tendency to give money to an anonymous individual) has been previously associated with poorer performance on neuropsychological tests sensitive to cognitive changes occurring in early Alzheimer’s disease (AD). While these findings provide initial support for the idea that financial altruism may be associated with early AD-related brain changes, no study has used MRI to investigate structural brain correlates of financial altruism in older adults. To address this gap in the literature, the current study investigated associations between brain macrostructure and financial altruism in 101 older adults free from dementia (mean age = 68.45±7.15, mean education = 16.61±2.14, 76% female, 73% White) using a high-field 7 Tesla MRI. Results revealed no significant associations between financial altruism and a priori regions of interest (entorhinal cortex, hippocampus, ventromedial prefrontal cortex, dorsolateral prefrontal cortex, and temporoparietal junction) in the entire sample. However, there was a significant interaction between financial altruism and income, whereby greater financial altruism was associated with lower hippocampal volume in those with a reported income below $100,000. Collectively these results suggest that financial altruism in the context of lower income, but not financial altruism in general, may reflect suboptimal brain aging, and perhaps greater risk of conversion to AD.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11682-026-01133-x.},
}

@article {pmid41845445,
year = {2026},
author = {Joost, S and Kaddatz, H and Vankriekelsvenne, E and Brandenburg, LO},
title = {The meninges as a neuroimmune interface: structure, barriers and roles in CNS disease.},
journal = {Fluids and barriers of the CNS},
volume = {23},
number = {1},
pages = {},
pmid = {41845445},
issn = {2045-8118},
abstract = {The meninges form a highly specialized barrier and immune interface that protects the central nervous system (CNS), regulates cerebrospinal fluid (CSF) dynamics, and coordinates communication between the CNS and the periphery. Each layer—dura mater, arachnoid mater and pia mater—possesses distinct structural, vascular and immunological features that collectively shape CNS homeostasis. A broad range of anatomical and molecular studies has revealed that meningeal compartments are far more heterogeneous and functionally complex than traditionally recognized, particularly with respect to their barrier architecture and immune interactions. In this review, we summarize current knowledge of meningeal structure and function, with a focus on barrier properties and immune-cell trafficking. We further discuss how meningeal dysfunction contributes to pathology in bacterial meningitis, multiple sclerosis and Alzheimer’s disease. Emerging evidence highlights the meninges as an active neuroimmune organ rather than a passive covering, critically influencing inflammation, solute clearance and disease progression. Understanding these mechanisms may open new therapeutic avenues targeting meningeal pathways across neurological disorders.},
}

@article {pmid41851041,
year = {2026},
author = {Kundu, P and Zhu, C and Huentelman, M and Deoni, SCL and Naymik, M and Taguinod, F and De Both, M and Lewis, CR and Müller, HG},
title = {Brain volume trajectories in young children are associated with polygenic scores for late-onset Alzheimer's disease risk.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {3},
pages = {e71279},
doi = {10.1002/alz.71279},
pmid = {41851041},
issn = {1552-5279},
support = {DMS-2014626//National Science Foundation/ ; DMS-2310450//National Science Foundation/ ; },
mesh = {Humans ; *Alzheimer Disease/genetics/pathology/diagnostic imaging ; Magnetic Resonance Imaging ; Male ; Female ; *Brain/pathology/diagnostic imaging/growth & development ; Child, Preschool ; *Multifactorial Inheritance/genetics ; *Genetic Predisposition to Disease/genetics ; Longitudinal Studies ; Organ Size ; Gray Matter/diagnostic imaging/pathology ; Child ; Genome-Wide Association Study ; White Matter/pathology/diagnostic imaging ; Cohort Studies ; },
abstract = {INTRODUCTION: Polygenic risk scores (PRSs) for Alzheimer's disease (AD) capture an individual's genetic susceptibility to AD. Although thoroughly studied in older populations, there exists a notable gap in comprehensively exploring the association of AD PRS with early brain development.

METHODS: We examined longitudinal brain magnetic resonance imaging (MRI) data from 348 typically developing children in the RESONANCE cohort. Proportional cerebrospinal fluid (pCSF), white matter (pWM), and gray matter (pGM) volumes were analyzed using functional concurrent regression and Riemannian functional principal component analysis. AD-PRS scores (AD25 and AD54) were computed using genome-wide data.

RESULTS: Higher AD PRS was significantly associated with reduced pCSF during early childhood (ages 2.5 to 5.5 years for AD54). Energy and distance-based tests revealed overall significant differences in brain volume trajectories between moderate and low AD54 risk groups.

DISCUSSION: These findings suggest that genetic risk for late-onset AD is linked to early neurodevelopmental patterns, indicating that AD vulnerability may originate during critical windows of early brain maturation.},
}

Humans
*Alzheimer Disease/genetics/pathology/diagnostic imaging
Magnetic Resonance Imaging
Male
Female
*Brain/pathology/diagnostic imaging/growth & development
Child, Preschool
*Multifactorial Inheritance/genetics
*Genetic Predisposition to Disease/genetics
Longitudinal Studies
Organ Size
Gray Matter/diagnostic imaging/pathology
Child
Genome-Wide Association Study
White Matter/pathology/diagnostic imaging
Cohort Studies

@article {pmid41851074,
year = {2026},
author = {Luo, X and Jia, L and Cao, J and Guo, Q and , and Chen, J and Zhao, XM},
title = {Identification of plasma biomarkers in lipid metabolism for accurate prediction of Alzheimer's disease.},
journal = {Translational psychiatry},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41398-026-03933-7},
pmid = {41851074},
issn = {2158-3188},
support = {32200537//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
abstract = {Metabolomics may reveal non-invasive biomarkers for early diagnosis in Alzheimer's disease (AD) and provide new insights into the disease mechanisms to develop effective treatments. Here, we comprehensively analyzed the blood plasma metabolomes from a Chinese cohort of 447 individuals, including 188 AD, 181 MCI (mild cognitive impairment), and 78 NC (normal control). Differential analysis identified altered metabolites, followed by forward feature selection to prioritize a panel of key metabolites, and construction of a diagnostic model using logistic regression. Key metabolite-enriched pathways were identified and quantified for comparison across different groups, which was then validated through external datasets. We observed extensive metabolic dysregulation in AD compared to age-matched NC, with 25% of the differential metabolites also significantly dysregulated in MCI in the same directions. A panel of 22 key metabolites was prioritized, where triglycerides (TG) and phosphatidylethanolamines (PE) ranked top in importance. With these key metabolites, we trained a diagnostic model that classified AD from NC accurately (Area Under the Curve [AUC] = 0.935 in the replication cohort). Pathway quantification analysis showed significant changes in lipid metabolism in AD, which were validated in two external cohorts. We presented a precise and robust blood metabolic diagnostic model for AD, which may help promote early diagnosis and deepen the understanding of AD mechanisms.},
}

@article {pmid41851083,
year = {2026},
author = {Zhang, W and Raghavan, S and Tian, J and Przybelski, SA and Wiste, HJ and Fought, AJ and Senjem, ML and Schwarz, CG and Reid, RI and Machulda, MM and Petersen, RC and Graff-Radford, J and Jack, CR and Lowe, VJ and , and Vemuri, P},
title = {Divergent white matter metabolic signature patterns indicate impending cognitive decline in aging and dementia.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-70707-6},
pmid = {41851083},
issn = {2041-1723},
abstract = {White matter (WM) is a key substrate for interregional neural communication and cognitive function but the role of WM glucose metabolism in cognitive aging has been understudied. Using multimodal neuroimaging (MRI, FDG-PET, amyloid-PET) from 3142 participants (15,287 visits) across two studies, we examined the contribution of WM to cognition and identified divergent WM signatures. Higher glucose metabolism in expected WM (EWM; corpus callosum and cingulum) was associated with better cognition, whereas increased metabolism in atypical WM (AWM; corona radiata) was linked to worse cognition, indicating a compensatory mechanism. EWM metabolism declined with aging, Alzheimer's disease (AD) progression (amyloid-β and APOE-ε4 carrier), and white matter hyperintensities, while AWM metabolism increased with aging and vascular risk but was partially weakened by AD neuropathology. Longitudinally, higher EWM and lower AWM metabolism predicted slower cognitive decline. Divergent WM metabolic patterns shed light on the dynamic role of WM in maintaining cognitive function. This study emphasizes the complementary information provided by WM metabolism for predicting future cognitive decline and identifying cognitive resilience.},
}

@article {pmid41851126,
year = {2026},
author = {D'Anniballe, VM and Kim, S and Finlay, JB and Wang, M and Ko, T and Luo, S and Whitson, HE and Johnson, KG and Goldstein, BJ},
title = {Olfactory cleft biopsy analysis of Alzheimer's disease pathobiology across disease stages.},
journal = {Nature communications},
volume = {17},
number = {1},
pages = {},
pmid = {41851126},
issn = {2041-1723},
support = {DC020172//U.S. Department of Health & Human Services | NIH | National Institute on Deafness and Other Communication Disorders (NIDCD)/ ; AG072958//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; R01 AG082335/AG/NIA NIH HHS/United States ; },
mesh = {Humans ; *Alzheimer Disease/pathology/cerebrospinal fluid/immunology/genetics ; Female ; Male ; *Olfactory Mucosa/pathology/metabolism/immunology ; Aged ; Biopsy ; CD8-Positive T-Lymphocytes/immunology ; Biomarkers/cerebrospinal fluid ; Middle Aged ; Aged, 80 and over ; Single-Cell Analysis ; Microglia/pathology ; Olfactory Receptor Neurons/pathology ; },
abstract = {Alzheimer's Disease (AD) is a neurodegenerative condition affecting millions worldwide. Defining early pathobiological events remains challenging, in part due to inaccessibility of neural tissue. Because olfactory neurons are accessible, and olfactory loss is prevalent in AD, we evaluated olfactory brush biopsies from controls, individuals with cerebrospinal fluid (CSF) biomarker-confirmed AD, and cognitively typical individuals whose positive CSF biomarkers signal a pre-clinical AD stage. Here we show via single cell RNA-sequencing (n = 22 subjects) conserved neuroinflammatory T cell, myeloid cell, and olfactory neuron changes detectable even in pre-clinical AD subjects, and corroborate heightened CD8 T-cell activation by flow cytometry. Activated memory T cell states in the olfactory epithelium were a hallmark of pre-clinical AD, paralleling CSF T cell phenotypes seen in advanced disease, accompanied by both microglia-like inflammatory programs and evidence of olfactory neuron inflammatory injury. Together, our findings establish a platform permitting analysis of neural tissue in AD at its earliest stages.},
}

Humans
*Alzheimer Disease/pathology/cerebrospinal fluid/immunology/genetics
Female
Male
*Olfactory Mucosa/pathology/metabolism/immunology
Aged
Biopsy
CD8-Positive T-Lymphocytes/immunology
Biomarkers/cerebrospinal fluid
Middle Aged
Aged, 80 and over
Single-Cell Analysis
Microglia/pathology
Olfactory Receptor Neurons/pathology

@article {pmid41851228,
year = {2026},
author = {Nasiri, H and Azimizonuzi, H and Khosravi, F and Hosseini, SF and Khoshrou, A and Rezakhani, S and Badri, R and Kazemi, D and Toorani, N and Soltanikhadiv, K and Behrouzieh, S and Alavi, SMA and Shakeri, S and Mayeli, M and Shahkarami, F},
title = {Associations between ventricular boundary shift integral and composite cognitive domains across the alzheimer's disease continuum.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-39465-9},
pmid = {41851228},
issn = {2045-2322},
}

@article {pmid41851356,
year = {2026},
author = {Saleem, T and Möbius, W and Schmitz, M and da Silva Correia, A and Thomas, C and Canaslan, S and Hermann, P and Göbel, S and Zafar, S and Root, E and Stadelmann, C and Andreoletti, O and Hoppert, M and Fleming Outeiro, T and Ferrer, I and Younas, N and Zerr, I},
title = {A distinct tau oligomer strain defines the molecular and proteomic landscape of rapidly progressive Alzheimer's disease.},
journal = {Acta neuropathologica},
volume = {151},
number = {1},
pages = {},
pmid = {41851356},
issn = {1432-0533},
mesh = {*Alzheimer Disease/metabolism/pathology/genetics ; *tau Proteins/metabolism ; Animals ; Humans ; Mice ; Proteomics ; Mice, Transgenic ; Male ; Disease Progression ; Female ; *Brain/metabolism/pathology ; Aged ; Cell Line, Tumor ; Phosphorylation ; Disease Models, Animal ; Aged, 80 and over ; },
abstract = {Rapidly progressive Alzheimer's disease (rpAD) is a rare subtype with rapid decline, but its molecular underpinnings remain poorly defined. Here, brain-derived tau oligomers (TauO) were systematically compared across nondemented controls, slowly progressive AD (spAD), and rpAD to test whether subtype-specific TauO signatures align with clinical aggressiveness. TauO were immunoprecipitated from frontal cortex using T22 antibody and characterized by Western blotting, transmission electron microscopy, label-free quantitative proteomics, and SH-SY5Y toxicity assays, complemented by longitudinal analysis of tau phosphorylation in inoculated 3xTg AD mice. T22-positive high-molecular-weight TauO were successfully enriched from all groups, where rpAD TauO exhibited compact, densely packed oligomers under TEM and the highest phosphorylation at pS396 and pS422, exceeding both spAD and controls (p ≤ 0.0327). In 3xTg mice, pS396 showed an early increase followed by a late decline, consistent with dynamic shifts in tau solubility during disease evolution. Brain-derived TauO from spAD and rpAD, but not recombinant tau monomers or control-derived TauO, significantly reduced SH-SY5Y cell viability. Proteomic profiling identified 2388 TauO-associated proteins, including a shared 556-protein core and a striking expansion of rpAD-unique interactors (n = 1101). In controls and spAD, the core TauO interactome was enriched for translation, proteostasis, mitochondrial respiration, and vesicle-trafficking pathways, whereas these modules were absent in rpAD. Instead, rpAD TauO showed selective enrichment of aldehyde detoxification, amino-acid and carbon metabolism, and actin-regulatory modules, alongside increased association of SERPINA1, ALDH9A1, MAPRE3, DPYSL2, DPYSL3, and NFASC and reduced coupling to mitochondrial (MRPL17) and complement (C9) components. These convergent structural, post-translational, toxic, and interactome changes indicate that rpAD is defined by a biochemically distinct TauO species embedded in a metabolic and cytoskeleton-focused network, providing a mechanistic framework for its aggressive clinical course and a basis for subtype-specific biomarker and therapeutic strategies.},
}

*Alzheimer Disease/metabolism/pathology/genetics
*tau Proteins/metabolism
Animals
Humans
Mice
Proteomics
Mice, Transgenic
Male
Disease Progression
Female
*Brain/metabolism/pathology
Aged
Cell Line, Tumor
Phosphorylation
Disease Models, Animal
Aged, 80 and over

@article {pmid41851792,
year = {2026},
author = {Zhang, JW and Li, R and Niu, YX and Liu, SY and Li, CH and Hao, XD and Wang, SH and Chen, S and Wang, FY},
title = {Clinical, neuroimaging, and biomarker profiling of four Alzheimer's disease pedigrees caused by pathogenic APP variants.},
journal = {Alzheimer's research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13195-026-02016-5},
pmid = {41851792},
issn = {1758-9193},
support = {82171196//the National Natural Science Foundation of China/ ; 241111313500//the Key Research and Development Program of Henan Province/ ; SBGJ202402012//the Medical Science and Technology Research Project of Henan Province/ ; },
}

@article {pmid41851829,
year = {2026},
author = {Gupta, A and Thirugnanam, K and Bice, Z and Lowman, AK and Rarick, KR and LaViolette, PS and Pan, A and Franczak, M and Ramchandran, R},
title = {Ciliary p75 neurotrophin receptor (p75NTR) facilitates the enrichment of exogenous amyloid beta (Aβ 1-42) peptide and promotes oxidative stress in human hippocampal astrocytes.},
journal = {BMC molecular and cell biology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12860-026-00581-z},
pmid = {41851829},
issn = {2661-8850},
support = {R33HL154254 and R01HL179583/NH/NIH HHS/United States ; NA//Brain 5K Run/ ; NA//Ryan M. Schaller Foundation/ ; },
}

@article {pmid41851960,
year = {2026},
author = {Bhoopal, B and Gollapelli, KK and Damuka, N and Krizan, I and Miller, M and Fitzgerald, RW and Amesar, N and Mumbaraddi, D and Zhu, D and Cervera-Juanes, R and Jadiya, P and Whitlow, CT and Solingapuram Sai, KK},
title = {Synthesis, Radiochemistry, and Preclinical Assessment of the First GPR39 PET Imaging Agent.},
journal = {Journal of medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jmedchem.5c03351},
pmid = {41851960},
issn = {1520-4804},
abstract = {GPR39 is a zinc-sensing G protein-coupled receptor with critical roles in neurophysiological and metabolic processes across brain, pancreas, gut, liver, and fat tissues. Activated by extracellular zinc ions, GPR39 is involved in neurodegenerative diseases including altered levels in Alzheimer's disease (AD). Quantifying GPR39 levels in vivo could significantly advance understanding of its role in various metabolic and disease processes, enabling drug development and treatment monitoring. Our study reports the synthesis, radiolabeling, and comprehensive preclinical evaluation of the first radiotracer for GPR39 imaging: [[11]C]TMN-OMe. The radiotracer demonstrated high radiochemical purity, molar activity, and stability in human serum. In vivo microPET/CT imaging, biodistribution, and autoradiography analyses confirmed selective binding to GPR39, with significantly reduced brain uptake in GPR39 knockout and AD mice, and in blockade conditions. Collectively, these findings support using [[11]C]TMN-OMe to quantify GPR39 levels in vivo and define GPR39-based imaging as a novel platform to study mechanistic changes in neurological disorders.},
}

@article {pmid41852022,
year = {2026},
author = {Nelson, LD and Simons, MU and Jain, S and Sun, X and Choi, K and Temkin, N and Diaz-Arrastia, R and Gardner, R and Taylor, S and Manley, GT and Stein, MB},
title = {Role of Polygenic Risk Scores in Predicting Cognitive Functioning after Mild Traumatic Brain Injury: A TRACK-TBI Study.},
journal = {Journal of neurotrauma},
volume = {},
number = {},
pages = {8977151261432398},
doi = {10.1177/08977151261432398},
pmid = {41852022},
issn = {1557-9042},
abstract = {Patients with traumatic brain injury (TBI) and Glasgow Coma Scale scores of 13-15 (historically called mild TBI [mTBI]) commonly experience changes in cognitive functioning, including processing speed, memory, and executive functioning. In a prospective sample (N = 523) of individuals of European descent who had been treated in a U.S. level 1 trauma center for mTBI, we examined the prognostic value of four polygenic risk scores (PRS) for cognitive outcomes at 6-months postinjury. To estimate the impact of mTBI on cognition, primary cognitive outcomes were scaled as z-scores reflecting changes in performance relative to predicted preinjury performance. The PRS examined were previously developed and validated to predict cognition-related outcomes of educational attainment (Education-PRS), intelligence (Intelligence-PRS), and Alzheimer's disease (AD-mild traumatic brain injury (APOE)-PRS and AD + APOE-PRS). Both the Education-PRS and Intelligence-PRS displayed bivariate associations with all four cognitive outcomes (β = 0.19-0.32), whereas neither Alzheimer's disease PRS was significantly associated with any outcome. After controlling for other factors known to predict cognitive outcomes of TBI (e.g., sex, education, mTBI severity defined by a combination of Glasgow Coma Scale scores and the presence/absence of acute intracranial findings on clinical neuroimaging), the Education-PRS and Intelligence-PRS remained independently predictive of verbal episodic memory (β = 0.10-0.16), whereas their associations with processing speed and executive functioning were mostly nonsignificant and were mediated through educational attainment. Looking across primary z-score and secondary raw score outcomes, cognitive outcomes 6 months post-mTBI were good on average, and PRS made small independent contributions to outcome prediction. The mediation model findings may support theories of cognitive reserve, which propose that individuals with stronger preinjury cognitive processing abilities (often estimated by educational history) can better compensate for TBI. Moreover, findings indicate that PRS may contribute modestly to multivariable models predicting cognitive function after TBI.},
}

@article {pmid41852095,
year = {2026},
author = {Zecca, V and Palombelli, G and Vanacore, N and Canese, R},
title = {The Role of Magnetic Resonance Spectroscopy (MRS), Diffusion-Tensor-Imaging (DTI) and Structural MRI in the Alzheimer's Disease and Mild Cognitive Impairment Diagnosis: A Review.},
journal = {Journal of magnetic resonance imaging : JMRI},
volume = {},
number = {},
pages = {},
doi = {10.1002/jmri.70296},
pmid = {41852095},
issn = {1522-2586},
abstract = {Alzheimer's disease (AD) is one of the most common neurological disorders affecting older adults, with approximately 7.2 million cases only in the United States. This number is projected to increase to 13.8 million in the United States by 2060, leading to increased expenditures for healthcare, long-term care and hospice services. Consequently, great emphasis is placed on prevention and the development of early diagnosis techniques, which can lead to timely treatment and the prevention of the consequences of full-blown disease. In this review, we analyze the potential diagnostic value of biomarkers derived from a multimodal approach based on magnetic resonance spectroscopy, diffusion tensor imaging, and magnetic resonance imaging, capable of detecting metabolic, microstructural, and anatomical changes, respectively, that precede the cognitive and behavioral changes observed in AD by years. The primary aim is to evaluate whether the combined and complementary use of these methods can identify early biomarkers useful for recognizing AD in its early stages, predicting progression from MCI to AD, supporting patient stratification, and monitoring cognitive decline or response to treatment. We identified regions more susceptible to metabolic alterations (PCC and hippocampus) and trajectories of structural brain alterations (atrophy or diffusivity abnormalities). The assessment of such imaging biomarkers may serve as the foundation for future prospective studies aimed at developing differential diagnostic methods, a crucial goal within the broader context of dementias, by adopting standardized multimodal MRI protocols. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 1.},
}

@article {pmid41852097,
year = {2026},
author = {Chen, L and Liu, YL and Cao, YG and Chen, L and Zheng, XK and Feng, WS},
title = {Discovery of Novel Flavonoids From Paeonia × suffruticosa Andr. and Their Acetylcholinesterase Inhibitory Activity.},
journal = {Chemistry & biodiversity},
volume = {23},
number = {3},
pages = {e03164},
doi = {10.1002/cbdv.202503164},
pmid = {41852097},
issn = {1612-1880},
support = {[2016]149//Central Government Guide Local Science and Technology Development Special Foundation/ ; ZYQR201810080//Henan Province High-level Personnel Special Support/ ; },
mesh = {*Cholinesterase Inhibitors/chemistry/isolation & purification/pharmacology ; *Flavonoids/chemistry/isolation & purification/pharmacology ; *Acetylcholinesterase/metabolism ; *Paeonia/chemistry ; Structure-Activity Relationship ; Molecular Structure ; Humans ; *Drug Discovery ; Dose-Response Relationship, Drug ; Molecular Docking Simulation ; Plant Roots/chemistry/metabolism ; Plant Bark/chemistry/metabolism ; },
abstract = {Three previously undescribed flavonoids, mudanpi A-C (1-3), and a new tetralin glycoside, suffruticoside M (4), along with 12 known compounds (5-16), were isolated from the dried root bark of Paeonia × suffruticosa Andr. Their structures were identified by spectroscopic analyses and computational methods. Given that studies have shown the therapeutic potential of Paeonia × suffruticosa Andr. extract against Alzheimer's disease, we evaluated the acetylcholinesterase inhibitory activity of its isolated compounds. Notably, compounds 2, 6, and 10 exhibited interesting acetylcholinesterase (AChE) inhibitory properties in vitro assays with the IC50 values of 8.95 ± 0.86, 7.69 ± 1.01, and 8.62 ± 0.12 µM, respectively.},
}

*Cholinesterase Inhibitors/chemistry/isolation & purification/pharmacology
*Flavonoids/chemistry/isolation & purification/pharmacology
*Acetylcholinesterase/metabolism
*Paeonia/chemistry
Structure-Activity Relationship
Molecular Structure
Humans
*Drug Discovery
Dose-Response Relationship, Drug
Molecular Docking Simulation
Plant Roots/chemistry/metabolism
Plant Bark/chemistry/metabolism

@article {pmid41852131,
year = {2026},
author = {Jin, MX and Qiu, JY and Jiang, HY},
title = {Marine-Derived Chitosan Oligosaccharides and Their Derivatives: A New Hope for Alzheimer's Prevention and Treatment - A Critical Review.},
journal = {Chemistry & biodiversity},
volume = {23},
number = {3},
pages = {e02777},
doi = {10.1002/cbdv.202502777},
pmid = {41852131},
issn = {1612-1880},
support = {81760207//National Natural Science Foundation project/ ; 2024AY10021//Jiaxing Municipal Public Welfare Research Program Project/ ; },
mesh = {*Alzheimer Disease/drug therapy/prevention & control/metabolism ; *Chitosan/chemistry/pharmacology/therapeutic use ; Humans ; *Oligosaccharides/chemistry/pharmacology/therapeutic use ; Animals ; *Aquatic Organisms/chemistry ; Antioxidants/chemistry/pharmacology ; *Neuroprotective Agents/chemistry/pharmacology ; Acetylcholinesterase/metabolism ; },
abstract = {Alzheimer's disease (AD) is a progressive degenerative disease of the central nervous system. Its clinical manifestations are mainly cognitive and memory disorders, and its incidence rate and mortality are increasing year by year. Chitosan oligosaccharides (COS), also known as β-1,4-oligoglucosamine, are natural alkaline polysaccharides and the only positively charged ones in nature. Due to its low molecular weight, good water solubility, and excellent biocompatibility, non-toxicity, and biodegradability, in recent years, it has received increasing attention from domestic and foreign researchers and enterprises. COS is of great significance in the prevention and treatment of AD; the main mechanisms of action include inhibiting acetylcholinesterase and beta-secretase activity, preventing abnormal phosphorylation of tau protein, chelating copper ions, protecting neuronal cells, and exhibiting antioxidant effects. This review primarily combines the latest research results, both domestic and international, to summarize and analyze the anti-AD effects and possible mechanisms of COS, aiming to provide the theoretical basis and the reference for the in-depth study of COS in the fields of biomedicine and functional foods and for its wider application in the fields of medicine and health food.},
}

*Alzheimer Disease/drug therapy/prevention & control/metabolism
*Chitosan/chemistry/pharmacology/therapeutic use
Humans
*Oligosaccharides/chemistry/pharmacology/therapeutic use
Animals
*Aquatic Organisms/chemistry
Antioxidants/chemistry/pharmacology
*Neuroprotective Agents/chemistry/pharmacology
Acetylcholinesterase/metabolism

@article {pmid41852247,
year = {2026},
author = {Ma, F and Özbay, PS and Bilgic, B and Hedden, T and Delman, B and Balchandani, P and Alipour, A},
title = {Optimized Quantitative Susceptibility Mapping at 7T MRI for Assessing Iron Deposition in Alzheimer's Disease.},
journal = {NMR in biomedicine},
volume = {39},
number = {4},
pages = {e70268},
doi = {10.1002/nbm.70268},
pmid = {41852247},
issn = {1099-1492},
support = {AG075178-0//NIH/NIA/ ; AG071179//NIH/NIA/ ; P30 AG066514/AG/NIA NIH HHS/United States ; },
mesh = {Humans ; *Alzheimer Disease/diagnostic imaging/metabolism ; *Magnetic Resonance Imaging ; *Iron/metabolism ; Male ; Female ; Aged ; Algorithms ; Middle Aged ; Brain/diagnostic imaging/metabolism ; },
abstract = {Elevated brain iron levels are common in Alzheimer's disease (AD). Quantitative susceptibility mapping (QSM) is an advanced MRI technique for assessing iron accumulation. The optimized QSM at 7 Tesla (7T) MRI may further improve the sensitivity to detect subtle susceptibility changes in AD. We optimized a QSM processing pipeline for 7T MRI by systematically comparing multiple reconstruction algorithms. Evaluation criteria included image quality, artifact suppression, and anatomical clarity. The finalized pipeline was applied to individuals with AD and healthy controls (HCs). The results revealed significantly elevated magnetic susceptibility values in the globus pallidus and dentate nucleus of the AD group compared to HCs. These findings were confirmed through both visual inspection and quantitative analysis of high-resolution QSM maps. This study provides a systematic evaluation and optimization of QSM processing pipelines at 7T MRI, offering improved sensitivity and reliability for detecting ad-related susceptibility alterations. Our results highlight the importance of optimizing QSM pipelines at 7T for accurate susceptibility quantification. AD patients exhibited higher susceptibility than controls in the globus pallidus (98.7-102.9 ppb) and dentate nucleus (51.1-52.8 ppb), consistent across all QSM pipelines. We identified an optimal pipeline suitable for future applications in patients with AD and other neurological conditions.},
}

Humans
*Alzheimer Disease/diagnostic imaging/metabolism
*Magnetic Resonance Imaging
*Iron/metabolism
Male
Female
Aged
Algorithms
Middle Aged
Brain/diagnostic imaging/metabolism

@article {pmid41852471,
year = {2026},
author = {Wu, J and Li, J and Qin, X and Chen, W},
title = {Association between diabetes mellitus and risk of Alzheimer's disease: a meta-analysis and systematic review.},
journal = {Frontiers in endocrinology},
volume = {17},
number = {},
pages = {1736410},
pmid = {41852471},
issn = {1664-2392},
mesh = {Humans ; *Alzheimer Disease/epidemiology/etiology ; *Diabetes Mellitus/epidemiology ; Risk Factors ; },
abstract = {BACKGROUND: Diabetes mellitus (DM) is hypothesized to increase the risk of Alzheimer's disease (AD). However, existing studies have yielded conflicting results, with some demonstrating a significant association between DM and AD risk while others have not. Therefore, this meta-analysis aimed to systematically evaluate the association between DM and AD risk.

METHODS: Comprehensive searches were conducted in PubMed, Web of Science, and Embase databases to identify cohort or case-control studies investigating the association between DM and AD risk. All eligible studies published before October 2025 were included. The Newcastle-Ottawa Scale (NOS) was used to assess the risk of bias. Hazard ratio (HR) and 95% confidence interval (CI) were pooled as the effect size for meta-analysis. Heterogeneity among studies was evaluated using Cochran's Q test and I [2] statistics. Statistical analyses were performed with RevMan 5.3 software.

RESULTS: A total of 11 studies involving 3,393,545 participants were included. A meta-analysis revealed that DM was significantly associated with an increased risk of AD (HR = 1.36, 95% CI (1.19, 1.55), P < 0.00001). A subgroup analysis showed that DM increased the risk of AD regardless of sample size (<100,000: HR = 1.33, 95% CI (1.11-1.59), P = 0.002; >100,000: HR = 1.39, 95% CI (1.13-1.71), P = 0.002). The consistency in P-values may be coincidental, and the results should be interpreted in conjunction with the high heterogeneity across studies. This association was consistent in both Asian (HR = 1.45, 95% CI: 1.20-1.76, P < 0.00001) and non-Asian populations (HR = 1.29, 95% CI: 1.13-1.48, P < 0.00001). After adjusting for APOE ϵ4 mutations, there was no statistically significant difference in the risk association between DM and AD (HR = 1.07, 95% CI (0.97-1.19), P = 0.177), whereas without adjustment for APOE ϵ4 mutation, DM was associated with an increased AD risk (HR = 1.42, 95% CI (1.23-1.64), P < 0.00001).

CONCLUSION: This meta-analysis provides compelling evidence that DM is an independent risk factor for AD, offering important implications for clinical practice and future research. However, due to the methodological limitations of this study, the results should be interpreted with caution. Large-scale, high-quality prospective cohort studies are needed to fully investigate the relationship between DM and AD risk.

https://www.crd.york.ac.uk/prospero/, identifier CRD420251159844.},
}

Humans
*Alzheimer Disease/epidemiology/etiology
*Diabetes Mellitus/epidemiology
Risk Factors

@article {pmid41852521,
year = {2026},
author = {Yuan, C and Acosta-Rodriguez, H and Elsaid, NMH and Weber, CF and Bobba, P and Tran, AT and Malhotra, A and Payabvash, S},
title = {Neuroimaging Correlates of the NIH Toolbox Cognition and Trail Making Tests: Normative Benchmarks in Healthy Aging.},
journal = {Clinical and translational neuroscience},
volume = {10},
number = {1},
pages = {},
pmid = {41852521},
issn = {2514-183X},
abstract = {The National Institutes of Health (NIH) Toolbox cognition battery and Trail Making Tests (TMT) are widely used to quantify cognitive aging and to detect early cognitive vulnerability in Alzheimer's disease and related conditions. However, these tests are often treated as interchangeable markers of global cognition, despite likely differences in their dependence on specific brain systems, limiting interpretability across studies and clinical contexts. To address this gap, we examined associations between four commonly used cognitive measures-fluid cognition, crystallized cognition, TMT-A, and TMT-B-and multimodal MRI metrics in 725 healthy volunteers aged 36 to 100 years from the Human Connectome Project-Aging. Voxel-wise diffusion MRI and vertex-wise cortical thickness and volume analyses were adjusted for age, sex, and years of education. Higher crystallized and fluid cognition scores and faster TMT-A/B completion times were generally associated with greater white matter integrity. TMT-B showed the most extensive diffusion and cortical associations, involving major projection, commissural, and association pathways and frontoparietal and temporo-occipital cortices. TMT-A and crystallized cognition demonstrated intermediate, overlapping patterns, whereas fluid cognition showed only focal brainstem and limited cortical correlates. These findings demonstrate systematic differences in the neuroanatomical substrates underlying commonly used cognitive tests and provide normative structure-cognition reference maps that can improve test selection, mechanistic interpretation, and sensitivity to brain health in studies of aging, vascular risk, and preclinical neurodegenerative disease.},
}

@article {pmid41852591,
year = {2026},
author = {Sánchez-Soliño, O and Boroje, I and Yue, EX and Vinikoor-Imler, L},
title = {Diagnosis patterns among diverse populations with mild cognitive impairment and Alzheimer's disease in the USA.},
journal = {JAR life},
volume = {15},
number = {},
pages = {100067},
pmid = {41852591},
issn = {2534-773X},
abstract = {BACKGROUND: Rapid advancements in diagnostic biomarkers and criteria have created a complex and evolving environment for clinicians managing patients with cognitive complaints. Real-world data on current diagnostic processes used among diverse populations remains limited.

OBJECTIVES: This study aimed to investigate diagnostic patterns and use of diagnostic tests among U.S. adults with mild cognitive impairment, Alzheimer's disease, and/or dementia, stratified by gender, age, and race/ethnicity before clinical availability of blood-based biomarkers and the most recent diagnostic updates.

DESIGN: Retrospective, observational cohort study.

SETTING: The Optum® Market Clarity database from January 1, 2017, to September 30, 2021, was utilized.

PARTICIPANTS: 338,739 patients diagnosed with dementia, 81,267 with AD, and 179,419 with MCI were included in the analysis.

MEASUREMENTS: Demographics information identified from electronic health records at the time of diagnosis was utilized. Occurrence and timing of diagnostic tests was pulled from insurance claims and electronic health records.

RESULTS: Mean age at diagnosis was 69.3 years for MCI, 78.9 years for AD, and 78.6 years for dementia. Computerized tomography (CT) and magnetic resonance imaging (MRI) were used infrequently (MCI: MRI 16.6%, CT 17.5%; AD: MRI 9.0%, CT 18.4%; dementia: MRI 9.5%, CT 25.9%). Cerebrospinal fluid (CSF) biomarker tests and positron emission tomography (PET) were rarely used (MCI: PET 0.6%, CSF 1.6%; AD: PET 0.5%, CSF 0.9%; dementia: PET 0.2%, CSF 1.6%).

CONCLUSIONS: During the study period, diagnosis of MCI, AD, and dementia involved low use of brain imaging or CSF biomarkers, despite recommendations from guidelines. By better understanding how patients navigate their diagnostic journey in real-world settings, diagnostic practices can improve and faster support can be provided.},
}

@article {pmid41852627,
year = {2026},
author = {Toledano-Pinedo, M and Iriepa, I and Rodríguez-Fernández, MM and Marco-Contelles, J},
title = {Masupirdine, a Selective Serotonin 5‑HT6 Receptor Antagonist for Alzheimer's Disease.},
journal = {ACS pharmacology & translational science},
volume = {9},
number = {3},
pages = {761-763},
pmid = {41852627},
issn = {2575-9108},
abstract = {Masupirdine is an oral, small, and safe molecule, readily available by a robust, two-step synthetic scheme, showing a potent, selective serotonin 5-HT6 receptor antagonist profile, pro-cognitive effects in various behavioral animal models in Phase 3 clinical trials for the treatment of agitation in patients with Alzheimer's dementia.},
}

@article {pmid41852647,
year = {2026},
author = {Shoff, TA and Derbez-Morin, M and Cai, P and Julian, RR},
title = {The microtubule nexus linking amyloid beta and tau: A simple and unifying theory for the underlying cause of Alzheimer's disease.},
journal = {PNAS nexus},
volume = {5},
number = {3},
pages = {pgag034},
pmid = {41852647},
issn = {2752-6542},
abstract = {Alzheimer's disease (AD) is defined by cognitive decline in conjunction with accumulation of aggregated amyloid β (Aβ) and tau, yet existing models of AD fail to provide a simple connection between Aβ and tau. However, microtubules provide an intriguing nexus for pathological interactions between the two. Tau binds to microtubules and is critical to maintaining their proper function. We demonstrate that Aβ also binds to microtubules with affinity comparable to that of tau itself. We hypothesize that displacement of tau by Aβ leads to microtubule dysfunction and facilitates tau phosphorylation and aggregation. Importantly, in this model, aggregation of Aβ is not the primary cause of toxicity, which allows many of the apparent contradictions between Aβ pathology and cognition to be rationalized. This model highlights the importance of both tau and Aβ and enables additional therapeutic and intervention strategies to be considered.},
}

@article {pmid41852829,
year = {2026},
author = {Guizzaro, L and Bałkowiec-Iskra, E and Haberkamp, M and Mol, PGM and Moreau, A and Mueller-Berghaus, J and Philadelphy, D and Balabanov, P and Garcia, J and Thirstrup, S and Sepodes, B},
title = {Balancing benefit and risk in early Alzheimer's disease: the European Medicines Agency (EMA) assessment of lecanemab and donanemab.},
journal = {The Lancet regional health. Europe},
volume = {63},
number = {},
pages = {101644},
pmid = {41852829},
issn = {2666-7762},
abstract = {Alzheimer's disease (AD) remains the leading cause of dementia in Europe, with limited therapeutic options despite decades of research. Recent regulatory approvals of lecanemab and donanemab in the EU mark a significant milestone. Both antibodies, developed within the amyloid hypothesis, demonstrated statistically significant effects on cognitive and functional outcomes in patients with early AD, though the clinical meaningfulness of these effects remains debated. There are also important safety concerns, particularly amyloid-related imaging abnormalities (ARIA), which resulted in difficult benefit-risk assessments. The Personal View describes some of the lines of evidence considered by the European Medicines Agency in the assessment of efficacy of these medicines, and some of the measures to ensure their safe use. While these therapies do not halt disease progression, and have substantial risks, they represent a step toward more transformative treatments. Future research, including real-world evidence studies, should refine patient selection, optimise monitoring, and explore combination approaches and new targets to achieve improved outcomes.},
}

@article {pmid41853003,
year = {2026},
author = {Khushi, P and Parmar, NJ and Daga, R and Sethumadhavan, J and Kale, PK and Laddha, R},
title = {Neuroprotectants: The Next Frontier in Neurology.},
journal = {Journal of pharmacy & bioallied sciences},
volume = {18},
number = {Suppl 1},
pages = {S1-S3},
pmid = {41853003},
issn = {0976-4879},
abstract = {Neuroprotectants are drugs or substances that help protect the brain and nerves from damage caused by injuries or diseases like stroke, Alzheimer's disease, and Parkinson's disease. This review looks at different types of neuroprotective agents, including those that reduce inflammation, prevent cell death, or improve blood flow to the brain. While many of these substances show good results in lab studies, only a few have been successful in human trials. This is often due to problems like delayed treatment, difficulty reaching the brain, and differences between patients. The review also discusses future clinical trials and how new technologies and targeted treatments may improve outcomes. Understanding how these agents work and how to test them better could lead to more effective treatments for brain disorders.},
}

@article {pmid41853044,
year = {2026},
author = {Hosseini, SA and Aumont, E and Rahmouni, N and Woo, MS and Macedo, AC and Hall, B and Trudel, L and Chan, T and Fernandez Arias, J and Wang, YT and Servaes, S and Therriault, J and Zheng, Y and Socualaya, KQ and Bezgin, G and Tissot, C and Oliva-Lopez, D and Hopewell, R and Hsiao, CH and Saleh, C and Stevenson, J and Lussier, F and Wu, L and Chu, M and Chawla, S and Fonov, V and Massarweh, G and Iturria-Medina, Y and Soucy, JP and Rudko, DA and Gauthier, S and Karikari, T and Benedet, AL and Ashton, NJ and Zetterberg, H and Montembeault, M and Vitali, P and Blennow, K and Collins, DL and Klostranec, J and Pascoal, TA and Rosa-Neto, P},
title = {Ventricular enlargement is associated with early Alzheimer's disease pathophysiology.},
journal = {Brain communications},
volume = {8},
number = {2},
pages = {fcag066},
pmid = {41853044},
issn = {2632-1297},
abstract = {Alzheimer's disease (AD) is characterized by progressive brain changes, including protein aggregation and structural changes. Cerebrospinal fluid (CSF) system abnormalities, such as ventricular dilation, increased choroid plexus volume or positron emission tomography (PET) ligand uptake in the CSF, have also been consistently described. We aimed to examine whether changes in CSF production and clearance might be associated with brain protein aggregation across biological stages of Alzheimer's disease. We hypothesized an association between brain protein aggregation and changes on the CSF system. We examined 378 individuals from the Translational Biomarkers in Aging and Dementia (TRIAD) cohort with T1-weighted magnetic resonance imaging (MRI), amyloid-PET and tau-PET assessments. We assessed the lateral ventricle and choroid plexus volumes, both corrected for intracranial volume, in the MRI native space. Non-specific ventricular tracer standardized uptake value ratio (SUVR), derived from amyloid- and tau-PET images, was used as an indirect marker of choroid plexus-related clearance activity and served as a metric of CSF dynamics. Linear models tested associations amongst lateral ventricular volume (reflecting CSF space enlargement), choroid plexus volume (reflecting secretory tissue morphology) and ventricular SUVR (reflecting tracer activity within the CSF compartment and serving as an indirect marker of choroid plexus-related clearance function and CSF dynamics) with Aβ and tau aggregations. Analyses were restricted to within-modality associations, relating ventricular radioactivity to cortical pathology for each PET tracer. We found that when considered independently, larger ventricular and choroid plexus volumes were associated with higher neocortical Aβ-PET SUVR, particularly in the precuneus and cingulate cortices. Additionally, lower ventricular radioactivity (derived from amyloid-PET) showed strong negative associations in the dorsal apex of the neocortex. However, when all three ventricular parameters were included in the same model, these effects were mediated by ventricular volume. By contrast, the effect of the ventricular parameters on tau load was mediated by Aβ in the neocortex. Therefore, ventricular enlargement appears to be associated with Aβ load. Distinct from neurodegeneration, changes in ventricular parameters, particularly ventricular volume, are associated with upstream Alzheimer's disease pathophysiology. While ventricular volume significantly mediated ventricular amyloid clearance, no such effect was observed for tau, suggesting distinct clearance mechanisms for these pathologies in Alzheimer's disease.},
}

@article {pmid41853174,
year = {2026},
author = {Chong, Y and Duan, C and Xu, X and Li, Z and Zhang, H and Gong, J and Wu, Q and Xia, L and Zhang, P and Xia, W},
title = {fNIRS-based early identification of mild cognitive impairment: a large-scale multi-paradigm study with ensemble machine learning models.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1738099},
pmid = {41853174},
issn = {1664-2295},
abstract = {BACKGROUND: Early and accurate identification of mild cognitive impairment (MCI) is crucial for timely intervention and preventing further cognitive decline. Functional near-infrared spectroscopy (fNIRS) is a non-invasive, portable tool for clinical screening, but its diagnostic accuracy is often constrained by single-paradigm approaches and small sample sizes. To address this limitation, this study aimed to develop and validate an efficient early MCI screening model by integrating large-sample fNIRS data from resting-state and 1-back task paradigms using ensemble machine learning, thereby enhancing the accuracy and reliability of early MCI diagnosis.

METHODS: A total of 462 right-handed participants (185 MCI patients and 277 healthy controls, aged 58 -87 years) were included in the final analysis after screening, with MCI diagnosis jointly determined by two experienced neurologists based on Petersen's criteria. fNIRS signals were collected during resting-state and 1-back task sessions; after preprocessing in MATLAB, features were extracted from oxygenated hemoglobin (HbO) signals of both paradigms.

RESULTS: Feature selection was performed via a gradient boosting classifier based on feature importance scores, resulting in 108 selected features. Five classifiers were trained and evaluated using 10-fold cross-validation. The integrated dataset combining resting-state and 1-back task features outperformed the single-paradigm datasets: the Neural Network model on this integrated dataset achieved an accuracy of 86.49%, sensitivity of 94.74%, specificity of 77.78%, and Area Under the Curve (AUC) of 93.49%. In contrast, the Nearest Neighbor model on the resting-state dataset and the Decision Tree model on the 1-back task dataset yielded accuracies of 70.27% and 75.68%, respectively. Group classification using MoCA scores achieved an accuracy of 86.55%, which was comparable to single-paradigm machine learning models but inferior to the integrated model.

DISCUSSION: This study demonstrates the value of a large-sample, data-driven approach and multi-paradigm feature integration in fNIRS-based MCI screening, providing an efficient diagnostic model for clinical application.

CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn/showprojEN.html?proj=192047.},
}

@article {pmid41853217,
year = {2026},
author = {Karthikeyan, A and Gopinath, N and Krishna, N and Joseph, A and Krishnamurthy, RG and Nair, BG},
title = {Neuroprotective potential of a novel marine metabolite from S. rhizophila BGNAK1 targeting acetylcholinesterase in Alzheimer's disease.},
journal = {3 Biotech},
volume = {16},
number = {4},
pages = {143},
pmid = {41853217},
issn = {2190-572X},
abstract = {UNLABELLED: Secondary metabolites from the marine bacterium Stenotrophomonas rhizophila strain BGNAK1 were evaluated for neuroprotective activity using biochemical and cellular assays relevant to Alzheimer's disease. The crude extract exhibited significant acetylcholinesterase (AChE) inhibitory activity with an IC50 value of 106.0163 µg/mL, indicating effective modulation of cholinergic function. Antioxidant evaluation revealed strong free radical scavenging capacity, with DPPH radical inhibition of and 97% at 1.0 mg/ml. The extract also significantly reduced intracellular reactive oxygen species levels, showing a reduction compared to untreated control cells at the highest tested concentration. Cytotoxicity analysis using PC12 and SH-SY5Y neuroblastoma cell lines demonstrated > 85% cell viability across all tested concentrations, confirming good biocompatibility. No significant morphological alterations or growth inhibition were observed under treatment conditions. Overall, these results demonstrate that metabolites derived from S. rhizophila BGNAK1 exert multi-target neuroprotective effects through combined cholinesterase inhibition and antioxidant mechanisms. Although direct neuronal injury models were not employed, the integrated biochemical and cellular findings provide quantitative evidence supporting the neurotherapeutic potential of marine bacterial metabolites and justify further investigation into their role in Alzheimer's disease-oriented drug discovery.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-026-04751-w.},
}

@article {pmid41853222,
year = {2026},
author = {Lassell, RKF and Carey, CJ and Sample, L and Elftmann, H and Gitlin, LN and Harezlak, J and Holden, RJ and Pearson, AL and Jordan, E and Keith, N and Unroe, K},
title = {Which activity tracker features matter to you? Older Black participants living with memory challenges and care partner preferences.},
journal = {Innovation in aging},
volume = {10},
number = {4},
pages = {igag011},
pmid = {41853222},
issn = {2399-5300},
abstract = {BACKGROUND AND OBJECTIVES: There is a need to understand Black older adults' perceptions and attitudes about commercial activity trackers to measure and monitor outcomes in clinical trials. We sought to identify the preferred activity tracker features of Black older adults living with memory challenges or dementia and their care partners.

METHODS: Utilizing a mixed-methods convergent parallel design, 9 participants were recruited from Eskenazi Health in Indianapolis, Indiana. Data were collected through 2 focus groups with participants (n = 3) and care partners (n = 4), and a group interview with 1 participant and 2 care partners. The focus groups were guided by semi-structured interviews, whereas participants interacted with 4 common consumer activity tracking devices (Fitbit Inspire 3, Apple Watch SE, Polar Watch, Oura Ring Heritage). Audio recordings were analyzed using the Rapid Identification of Themes from Audio Recordings method. Participants ranked each device based on comfort, convenience, and features (eg, tracked outcomes of activity, distance/GPS, and respiratory rate). Device rankings were summarized with descriptive statistics.

RESULTS: Participants with memory challenges rated Apple Watch SE highest, with mean scores in comfort (4.3), convenience (3.3), and features (4.3). Care partners rated Fitbit Inspire 3 highest in comfort and Apple Watch SE for convenience and features. Qualitative findings highlighted physical attributes and comfort (large screen size), convenience (viewing progress), and features (having an emergency button and GPS).

DISCUSSION AND IMPLICATIONS: Findings can guide the selection of activity trackers in future research for this population and may increase wear time and adherence in clinical trials.},
}

@article {pmid41853237,
year = {2026},
author = {Udayakumar, S and Metkar, SK and Girigoswami, K and Girigoswami, A},
title = {Potential effect of nanoformulated iota carrageenan in Aβ1-42 disaggregation: an in vitro, in vivo and in silico study.},
journal = {ADMET & DMPK},
volume = {14},
number = {},
pages = {3122},
pmid = {41853237},
issn = {1848-7718},
abstract = {BACKGROUND AND PURPOSE: Alzheimer's disease is the primary contributor to neurodegenerative conditions. These pathologies are identified by the deposition of β-amyloid peptide within brain regions. It develops insoluble fibrils known as senile plaques. These plaques are associated with synaptic dysfunction, neuroinflammation, and progressive cognitive decline. Hence, the degradation and elimination of β-amyloid peptide fibrils from the body are viable therapeutic approaches for managing Alzheimer's disease.

EXPERIMENTAL APPROACH: In the current study, liposomal nanoformulated iota carrageenan was synthesized and characterized using different photophysical tools. The nanoformulated iota carrageenan effectively degraded β-amyloid peptide 1-42, with 45.5 % reduction confirmed by Thioflavin T fluorescence assay. This activity was further supported by turbidity and dynamic light scattering analysis.

KEY RESULTS: The biocompatibility of nanoformulated iota carrageenan and its degraded β-amyloid peptide was determined using an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), live/dead cell assay on PC12 cells. Structural disintegration of the β-amyloid peptide fibrils was validated through atomic force microscopy, revealing a significant reduction in fibrillar morphology. In silico studies also evidenced the interaction between the β-amyloid peptide and nanoformulated iota carrageenan. In addition, the neuroprotective potential of nanoformulated iota carrageenan, as evidenced by nanoformulated iota carrageenan-treated β-amyloid peptide, was supported by neurite outgrowth studies. These studies showed that differentiated PC12 cells exhibited larger neurite growth with extensive branching, indicating the reversal of β-amyloid peptide-induced neurotoxicity. CAM assay demonstrated enhanced blood vessel formation in chick embryos treated with nanoformulated iota carrageenan and its β-amyloid peptide-degraded group.

CONCLUSION: These findings suggest that nanoformulated iota carrageenan holds potential and has nontoxic therapeutic effects for Alzheimer's disease. Additional in vivo validation is required in future investigations.},
}

@article {pmid41853467,
year = {2026},
author = {Teipel, S and Grazia, A and Peters, O and Priller, J and Schneider, A and Wiltfang, J and Bartels, C and Schott, BH and Jessen, F and Duezel, E and Yakupov, R and Buerger, K and Perneczky, R and Laske, C and Spottke, A and Wagner, M and Peltner, J and Kilimann, I and Haenisch, B},
title = {Associations of anticholinergic burden of medication with cognitive decline and longitudinal brain atrophy in the Alzheimer's disease spectrum.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1751326},
pmid = {41853467},
issn = {1663-4365},
abstract = {BACKGROUND: Anticholinergic side effects of pharmacological treatment are a risk factor for cognitive decline in older people. Here, we aimed to assess the effect of anticholinergic burden of treatment on longitudinal rates of cognitive change and atrophy in functionally related brain regions in people from the Alzheimer's disease (AD) spectrum.

METHODS: We determined associations of anticholinergic burden of pharmacological treatment with rates of global cognition, episodic memory and executive function decline as well as basal forebrain and hippocampus atrophy in participants of the memory clinic based DELCODE cohort, spanning the range from cognitively normal through subjective cognitive decline, mild cognitive impairment and AD dementia. We had 794 cases with neuropsychological outcomes, and a subset of 703 cases with MRI outcomes. Effects were assessed using mixed effect models in a Bayesian framework using prior-insensitive cross-validated Bayes factors (CV-BF) and parameter estimates.

RESULTS: We found moderate evidence for an association of anticholinergic burden with baseline levels of cognitive impairment for the PACC5 as a global cognitive function score (CV-BF = 9.0) with more impairments with higher burden, but not with basal forebrain and hippocampus volumes, and weak evidence for an association of anticholinergic burden with longitudinal rates of change in the trail-making test B as an executive function score (CV-BF = 2.5), but not for other cognitive scores and not for brain volumes.

CONCLUSION: In the presence of prodromal or manifest AD, in a memory clinic-based cohort anticholinergic burden had only a modest effect on cognitive decline and no effect on atrophy in brain regions that are related to the cholinergic system.},
}

@article {pmid41853673,
year = {2026},
author = {Avila-Villanueva, M and Hernández, F and Avila, J and Plascencia-Villa, G and Perry, G},
title = {Sensory deficiencies correlate with tau protein and dementia.},
journal = {Frontiers in neuroscience},
volume = {20},
number = {},
pages = {1754329},
pmid = {41853673},
issn = {1662-4548},
abstract = {Sensory decline is a common feature of aging and an early sign of a high risk of developing neurodegenerative diseases. Abnormal protein deposits of tau are also observed in sensorial areas in early stages of Alzheimer's disease and related dementia (ADRD), indicating that these two features are associated with common neuropathological changes in the affected brain areas. Alterations in taste and smell are evident in subjects with cognitive decline, but sensory decline is perceived in olfaction, vision, hearing (at early times of degeneration), and even touch, which correlates with disease progression. Consequently, affected individuals may suffer from varying altered behaviors that emerge from the declined capability to process and perceive information, suggesting that differences in sensory perception of the environment may play a key role in explaining these behavioral variations in subjects with cognitive impairment. This commentary discusses some of the alterations in sensory functionality and how these could contribute to the development of neurodegenerative disorders, such as ADRD.},
}

@article {pmid41853851,
year = {2026},
author = {Jun, JE and Kim, S and Jeong, IK and Kim, JH},
title = {Dementia Risk in Type 1 and 2 Diabetes: A Nationwide Population-Based Comparison.},
journal = {Diabetes, obesity & metabolism},
volume = {},
number = {},
pages = {},
doi = {10.1111/dom.70677},
pmid = {41853851},
issn = {1463-1326},
abstract = {AIMS: Diabetes is increasingly recognised as a major contributor to cognitive decline and dementia, but the risk varies by diabetes type and treatment intensity. We compared the risk of all-cause dementia, Alzheimer's disease (AD) and vascular dementia (VaD) among individuals with and without diabetes.

METHODS: This population-based retrospective cohort study analysed data from the Korean National Health Insurance Service (2013-2024). A total of 1 322 651 adults aged ≥ 40 years without prior dementia were included. Participants were classified as non-diabetic, type 2 diabetes (T2DM) with oral hypoglycemic agents (OHAs), T2DM with insulin, or type 1 diabetes (T1DM). Incident dementia was identified using ICD-10 codes and anti-dementia prescriptions. Multivariable Cox proportional hazards models adjusted for demographic, lifestyle and clinical factors estimated adjusted hazard ratios (aHRs) for dementia.

RESULTS: Dementia incidence rates per 1000 person-years were 4.3 (non-diabetic), 12.7 (T2DM with OHA), 17.9 (T2DM with insulin) and 21.1 (T1DM). Compared with non-diabetic participants, aHRs for all-cause dementia were 1.29 (95% CI 1.26-1.32) for T2DM with OHA, 2.14 (2.00-2.28) for T2DM with insulin and 2.35 (2.12-2.59) for T1DM. Similar trends were observed for AD and VaD. Dementia risk was highest in individuals with T1DM and insulin-treated T2DM, with no significant difference between these groups.

CONCLUSIONS: Diabetes was associated with a higher risk of dementia, particularly among individuals with T1DM and insulin-treated T2DM, suggesting that insulin-requiring diabetes represents a high-risk phenotype for cognitive decline. Proactive cognitive screening and optimised glycemic management, including strategies to reduce glycemic variability such as continuous glucose monitoring, may help mitigate dementia risk in these vulnerable populations.},
}

@article {pmid41853971,
year = {2026},
author = {Rae, RJ and Alberhasky, JMH and Baillet, M and Bangasser, DA and Belloy, ME and Berry, AS and Berteotti, C and Bow, H and Buckley, R and Caldwell, JZK and Carpi, M and Clark, BJ and Ciampa, CJ and Conley, AC and Dahl, MJ and Donaldson, ZR and Ehrenberg, AJ and Einstein, G and Falgàs, N and Fenlon, HA and Fitzhugh, MC and Froemke, RC and Gallay, C and Grinberg, LT and Hamilton, DA and Hasan, Z and Huarte, OU and Jabeen, S and Jacobs, HIL and Kolling, LJ and Koops, EA and Lenzoni, S and Liguori, C and Manca, R and Marcinkiewcz, CA and Omoluabi, T and Oria, R and Orsini, CA and Ortega, NE and Pa, J and Pentkowski, NS and Pereira, JB and Ramos, R and Sargin, D and Satpati, A and Selles, MC and Seto, M and Shaik, SM and Sindi, S and Son, G and Ucheagwu, V and Van Egroo, M and Yuan, Q and Kelberman, MA},
title = {Sex differences in neuromodulatory subcortical systems and their implications for Alzheimer's disease.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {3},
pages = {e71291},
doi = {10.1002/alz.71291},
pmid = {41853971},
issn = {1552-5279},
support = {//International Max Planck Research School on Computational Methods in Psychiatry and Ageing Research/ ; A2024006F//BrightFocus Foundation/ ; //Kissick Family Foundation/ ; #PJT-1691797/CAPMC/CIHR/Canada ; //Canadian Centre for Brain Health Innovation CABHI/ ; //Brain Canada/ ; //Women's Brain Health Initiative/ ; //Joan Rodes Fellowship/ ; JR22/00014//Instituto de Salud Carlos III/ ; //Rainwater Charitable Foundation/ ; //University of Calgary/ ; STEP Postdoctoral Fellowship//Alberta Children's Hospital Research Institute/ ; WE.03-2019-02//Alzheimer Nederland/ ; AARF-23-1026796/ALZ/Alzheimer's Association/United States ; AARG-22-917644/ALZ/Alzheimer's Association/United States ; AACSF-23-1145154/ALZ/Alzheimer's Association/United States ; AARG-22920434/ALZ/Alzheimer's Association/United States ; 101149449//Marie Curie Fellowship NINFA-AD GAP/ ; //Alzheimer Foundation/ ; 2022-014//Brain Foundation/ ; //European Union - NextGenerationEU/ ; 760250/28.12.2023//National Recovery and Resilience Plan for Romania through the Romanian Ministry of Research/ ; PNRR-C9-I8-CF109/31.07.2023//National Recovery and Resilience Plan for Romania through the Romanian Ministry of Research/ ; //Alzheimer's Society of Canada New Investigator Operating Grant/ ; //Foundation for Geriatric Diseases at Koralinska Institutet/ ; //Riksbankens Jubileumsfond/ ; 101109451-ADEEPSLEEP//European Union's Marie Skłodowska-Curie Actions/ ; //Loo and Hans Osterman Foundation for Medical Research/ ; //The Foundation for Geriatric Diseases at Koralinska Institutet/ ; //The Rut and Arvid Wolff Memorial Foundation/ ; //Alzheimerfonden/ ; //Wellcome Leap CARE/ ; //Alzheimer's Disease Research Center ADRC-AAC/ ; //Pew Charitable Trusts/ ; //Konung Gustaf V:s och Drottning Victorias Stiftelse/ ; //KI Consolidator grant/ ; Marie Curie Fellowship NINFA-AD GAP: 101149449/MCCC_/Marie Curie/United Kingdom ; UH2TR002082/TR/NCATS NIH HHS/United States ; HD088411//Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; IOS-2045348//National Science Foundation/ ; R01-MH125423/MH/NIMH NIH HHS/United States ; NS107616/NS/NINDS NIH HHS/United States ; U01-NS131406/NS/NINDS NIH HHS/United States ; R01-DA055676/DA/NIDA NIH HHS/United States ; F32-AG084196/AG/NIA NIH HHS/United States ; R01-AG068062/AG/NIA NIH HHS/United States ; R01-DA056534/AG/NIA NIH HHS/United States ; R34-DA061483/AG/NIA NIH HHS/United States ; R00-AG075238/AG/NIA NIH HHS/United States ; R01-AG074330/AG/NIA NIH HHS/United States ; R01-AG079142/AG/NIA NIH HHS/United States ; F31-AG085963/AG/NIA NIH HHS/United States ; K22-AG081276/AG/NIA NIH HHS/United States ; R01-AG060477/AG/NIA NIH HHS/United States ; R01-AG064314/AG/NIA NIH HHS/United States ; K24-AG053435/AG/NIA NIH HHS/United States ; R01-AG075802/AG/NIA NIH HHS/United States ; R01-AG062559/AG/NIA NIH HHS/United States ; R01-AG06806/AG/NIA NIH HHS/United States ; R01-AG082006/AG/NIA NIH HHS/United States ; R21-AG074220/AG/NIA NIH HHS/United States ; P50-AA022534/AA/NIAAA NIH HHS/United States ; #2022-01108//Swedish Research Council/ ; },
mesh = {Humans ; *Alzheimer Disease/physiopathology ; *Sex Characteristics ; Female ; Male ; *Brain/physiopathology ; },
abstract = {Neuromodulatory subcortical systems (NSSs) are uniquely susceptible to dementia-related pathology, leading to frequent molecular and behavioral impairments associated with altered function of these nuclei. Some of these systems display clear sex-specific cytoarchitecture and signaling leading to distinct physiology and behavioral outputs in males and females, while other regions display nominal sex differences. However, the relevance of sex differences in modulating dysfunction of NSSs in Alzheimer's disease (AD) and related dementias is not well understood. This review is a joint effort by the Neuromodulatory Subcortical Systems and Sex and Gender Differences in Alzheimer's Disease Professional Interest Areas of the Alzheimer's Association. We review sex differences in NSSs, both in non-disease states and in AD models and patients. We highlight the possible role of NSSs in driving sex-specific AD susceptibility and potential footholds for sex-based interventions targeting these systems. We conclude by outlining immediate and long-term actions to address the intersection of NSSs, sex, and AD.},
}

Humans
*Alzheimer Disease/physiopathology
*Sex Characteristics
Female
Male
*Brain/physiopathology

@article {pmid41853974,
year = {2026},
author = {Malik, S and De, I and Yadav, AS and Poonia, V and Gaur, K and Goyal, P and Singh, M and Yadav, JK},
title = {Inhibition of Aβ(40) peptide aggregation by Milk-derived Amyloid-like Protein Aggregates (MAPA).},
journal = {Biological chemistry},
volume = {},
number = {},
pages = {},
pmid = {41853974},
issn = {1437-4315},
abstract = {Recent studies have identified Aβ peptides in human gut epithelial cells, along with several amyloid-forming proteins and peptides in the gut lumen. These findings suggest that Aβ or other amyloid-like molecules originating from the gut may contribute to the involvement of the gastrointestinal system in the development of Alzheimer's disease (AD) pathology. Modulating the aggregation behaviour of Aβ and other amyloid forming peptides/proteins present in the gut may represent novel strategy to mitigate AD pathology. This study explores the use of Milk-derived Amyloid-like Protein Aggregates (MAPA) to inhibit Aβ(40) aggregation in vitro. MAPA's inhibitory effects were assessed using amyloid dye-binding assays (Thioflavin T, Congo Red, and ANS) and transmission electron microscopy. Toxicity assays showed that the MAPA significantly reduced Aβ(40)-induced neuronal death. Fluorescence quenching suggest MAPA physically interacts with Aβ(40) to prevent its aggregation. By blocking Aβ aggregation and reducing its neurotoxicity, MAPA presents a promising organic strategy to counteract AD progression influenced by gut factors. These findings open new avenues for AD prevention and the disease management, especially via dietary interventions targeting the gastro-intestinal system.},
}

@article {pmid41853978,
year = {2026},
author = {Piotrowski, SL and Allnutt, MA and Johnson, K and Tanaka, T and Ferrucci, L and Morris, H and Hardy, J and , and Ryten, M and , and Logroscino, G and Troncoso, J and Beach, TG and Serrano, GE and Cruchaga, C and Dickson, DW and Ross, OA and Chiò, A and , and , and Houlden, H and , and Dalgard, CL and Ding, J and Gibbs, JR and Traynor, BJ and Scholz, SW and Jacobson, S},
title = {Herpesvirus genome integration in whole-genome sequences of dementia and control cohorts.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {3},
pages = {e71047},
doi = {10.1002/alz.71047},
pmid = {41853978},
issn = {1552-5279},
support = {1ZIAAG000935/AG/NIA NIH HHS/United States ; P30AG019610/AG/NIA NIH HHS/United States ; P30AG072980/AG/NIA NIH HHS/United States ; U24AG021886/AG/NIA NIH HHS/United States ; P50AG016574/AG/NIA NIH HHS/United States ; U19AG071754/AG/NIA NIH HHS/United States ; R01AG087165/AG/NIA NIH HHS/United States ; U24 NS072026/NS/NINDS NIH HHS/United States ; 1ZIANS003154/NS/NINDS NIH HHS/United States ; U54-NS110435/NS/NINDS NIH HHS/United States ; P50NS072187/NS/NINDS NIH HHS/United States ; 211002//Arizona Department of Health Services/ ; 4001 0011 05-901//Arizona Biomedical Research Commission/ ; //Michael J. Fox Foundation for Parkinson's Research/ ; //Ted Turner and family/ ; //Little Family Foundation/ ; //Mayo Clinic Dorothy and Harry T. Mangurian Jr. Lewy body dementia program/ ; },
mesh = {Humans ; *Dementia/virology/genetics ; *Genome, Viral/genetics ; *Herpesvirus 6, Human/genetics ; *Virus Integration/genetics ; Cohort Studies ; Whole Genome Sequencing ; Aged ; Female ; Male ; *Herpesviridae/genetics ; Alzheimer Disease/virology/genetics ; },
abstract = {INTRODUCTION: The infectious hypothesis suggests that microbes like herpesviruses may play a role in the pathogenesis of Alzheimer's disease (AD) and other related dementias through methods that may include viral genome integration. The occurrence of herpesvirus genome integration in dementia patients has not been thoroughly characterized.

METHODS: Over 7500 total whole-genome sequences from control, frontotemporal dementia/amyotrophic lateral sclerosis spectrum, Lewy body dementia (LBD), multiple system atrophy (MSA), and AD cohorts were screened for the integration of pathogen genomes using the PathSeq computational tool.

RESULTS: Low PathSeq scores for human herpesvirus 6 (HHV-6) were consistent with the suspected integration of viral genome segments. The LBD and MSA cohorts had a significantly higher prevalence of this partial HHV-6 genome integration.

DISCUSSION: This higher prevalence in both synucleinopathies was not noted in other herpesviruses, suggesting that the integration of HHV-6 may play a role in a subset of these patients.

HIGHLIGHTS: Over 7500 whole-genome sequences from controls and dementia patients were analyzed. Sequences consistent with integrated herpesviruses were identified using PathSeq. Prevalence of partial HHV-6 integration was higher in synucleinopathies. Herpesviruses genome integration may play a role in subsets of dementia patients.},
}

Humans
*Dementia/virology/genetics
*Genome, Viral/genetics
*Herpesvirus 6, Human/genetics
*Virus Integration/genetics
Cohort Studies
Whole Genome Sequencing
Aged
Female
Male
*Herpesviridae/genetics
Alzheimer Disease/virology/genetics

@article {pmid41853992,
year = {2026},
author = {Vega-Quiroga, S and Bermejo-Pareja, F and Martín-Arriscado, C and Benito-León, J},
title = {Dementia incidence trends in rural Spain: Ten-year cohort findings from NEDICES cohort.},
journal = {The Journal of rural health : official journal of the American Rural Health Association and the National Rural Health Care Association},
volume = {42},
number = {1},
pages = {e70135},
doi = {10.1111/jrh.70135},
pmid = {41853992},
issn = {1748-0361},
support = {/NH/NIH HHS/United States ; TED2021-130174B-C33//The Recovery, Transformation and Resilience Plan at the Ministry of Science and Innovation/ ; NETremor//The Recovery, Transformation and Resilience Plan at the Ministry of Science and Innovation/ ; //The Spanish Health Research Agency and the Spanish Office of Science and Technology/ ; },
mesh = {Humans ; Spain/epidemiology ; Aged ; Male ; Female ; Incidence ; *Dementia/epidemiology ; *Rural Population/statistics & numerical data/trends ; Aged, 80 and over ; Cohort Studies ; },
abstract = {PURPOSE: To estimate dementia incidence in the rural population enrolled in the Neurological Diseases in Central Spain (NEDICES) cohort and to evaluate the impact of ascertainment strategies on temporal trend estimates.

METHODS: Residents aged ≥65 years were examined at baseline (1994-1995), in 1997-1998, and in 2004-2005. Incident dementia was identified through clinical reassessment, medical record review, and, for decedents between waves, via linkage to the Spanish National Death Registry. Person-time accrued from baseline to dementia, death, or censoring; incidence rates (per 1000 person-years) with 95% confidence intervals (CIs) were estimated using exact Poisson methods; incidence rate ratios (IRRs) contrasted 1994-1998 with 1999-2005.

FINDINGS: Of 2148 eligible residents in the 1993 census, 1937 were screened; 113 prevalent cases were excluded, leaving 1824 dementia-free participants. In 1994-1998, 60 incident cases occurred over 4427.3 person-years (13.6; 95% CI, 10.5-17.5): 41 detected at first follow-up, 13 reclassified at the third wave, and 6 identified from death certificates. In 1999-2005, 76 cases accrued over 2584.9 person-years (29.4; 95% CI, 23.3-36.9); 23 were actively ascertained, and 53 were registry-only, resulting in an IRR of 2.17 (95% CI, 1.55-3.04; p < 0.001). Restricting to actively ascertained cases, rates were 12.2 versus 8.9 (IRR = 0.73; 95% CI, 0.45-1.19; p = 0.20). Alzheimer's disease was the most frequent subtype.

CONCLUSIONS: The incidence increased only when death certificate diagnoses were included; active follow-up suggested stability. This higher incidence may reflect older age structure, lower educational attainment/cognitive reserve, heavier vascular risk burden, and constrained diagnostic access that shifts detection to death certification.},
}

Humans
Spain/epidemiology
Aged
Male
Female
Incidence
*Dementia/epidemiology
*Rural Population/statistics & numerical data/trends
Aged, 80 and over
Cohort Studies

@article {pmid41854004,
year = {2026},
author = {Zamagni, G and Armocida, B and Castelpietra, G and Conti, S and Cortesi, PA and Ferrara, P and Fornari, C and Gallus, S and Leonardi, M and Passera, R and Perico, N and Raggi, A and Remuzzi, G and Ronfani, L and Monasta, L},
title = {The burden of disease in Italy, 1990-2023: a subnational analysis from the Global Burden of Disease Study 2023.},
journal = {Epidemiologia e prevenzione},
volume = {50},
number = {1},
pages = {67-77},
doi = {10.19191/EP26.1.A991.020},
pmid = {41854004},
issn = {1120-9763},
mesh = {Humans ; Italy/epidemiology ; Male ; Female ; *Global Burden of Disease/trends ; *Life Expectancy/trends ; *Disability-Adjusted Life Years ; Aged ; Middle Aged ; *COVID-19/epidemiology ; Adult ; Aged, 80 and over ; Adolescent ; Infant ; Young Adult ; Child ; Child, Preschool ; Infant, Newborn ; *Cost of Illness ; Quality-Adjusted Life Years ; Sex Distribution ; },
abstract = {OBJECTIVES: to provide a comprehensive and comparable assessment of life expectancy (LE), health-adjusted life expectancy (HALE), Years Lived with Disability (YLDs), Years of Life Lost (YLLs), and Disability-Adjusted Life Years (DALYs) across Italian regions from 1990 to 2023, identifying temporal, geographical, and sex-specific patterns to inform targeted public health strategies.

DESIGN: descriptive epidemiological study using estimates from the Global Burden of Disease Study (GBD) 2023.

SETTING AND PARTICIPANTS: the analysis covered the Italian population, stratified by sex, five macro-regions, and 21 subnational locations, including 19 Regions and 2 Autonomous Provinces.

MAIN OUTCOME MEASURES: LE, HALE, all-age and age-standardized rates YLDs, YLLs, and DALYs per 100,000 population; all estimates were presented with their 95% uncertainty intervals.

RESULTS: between 1990 and 2023, LE increased substantially across all regions and in both sexes, despite the temporary decline associated with the COVID-19 pandemic. In 2023, the highest LE was recorded in the North-East, with 81.4 years (95%CI 81.1-81.6) for males and 85.8 years (95%CI 85.6-86.1) for females, while the lowest values were found in the Islands, at 79.7 years (95%CI 79.3-80.1) for males and 84.2 years (95%CI 83.9-84.5) for females. However, differences diminished when considering HALE. YLDs increased steadily over time, reflecting not only population ageing but also the expanding burden of chronic and non-fatal conditions. In contrast, YLLs declined markedly in both sexes, driven particularly by substantial reductions in mortality from neoplasms and cardiovascular diseases. However, in 2023, ischemic heart disease remained the leading contributor to all-age DALYs among males, while Alzheimer's disease was the top cause among females. Anxiety disorders represented the leading cause of age-standardized DALYs in females and showed marked increases since 1990. Among males, ischemic heart disease continued to appear as the primary cause of age-standardized DALYs.

CONCLUSIONS: health in Italy improved substantially over the past three decades, primarily due to declining premature mortality. However, the burden of disability increased, particularly among women, and important geographical and sex-specific inequalities persist. Strengthening prevention policies, addressing behavioural and metabolic risk factors and mental health, improving long-term care, and promoting healthy ageing are essential to reducing health disparities.},
}

Humans
Italy/epidemiology
Male
Female
*Global Burden of Disease/trends
*Life Expectancy/trends
*Disability-Adjusted Life Years
Aged
Middle Aged
*COVID-19/epidemiology
Adult
Aged, 80 and over
Adolescent
Infant
Young Adult
Child
Child, Preschool
Infant, Newborn
*Cost of Illness
Quality-Adjusted Life Years
Sex Distribution

@article {pmid41854019,
year = {2026},
author = {Fu, W and Chao, X and Wang, Y and Liu, S and Wang, J and Huang, Q and Luan, Y and Luo, P and Guan, Y and Mai, Y and Jia, W and , and Guo, Q and Chen, T and Ma, X and Xie, F},
title = {Bile acids are associated with baseline and longitudinal amyloid and tau pathology in patients with Alzheimer's disease.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {3},
pages = {e71307},
doi = {10.1002/alz.71307},
pmid = {41854019},
issn = {1552-5279},
support = {2022ZD0213800//STI2030-Major Projects/ ; 82201583//the National Science Foundation of China/ ; 82471441//the National Science Foundation of China/ ; 82071962//the National Science Foundation of China/ ; 82470853//the National Science Foundation of China/ ; 82270917//the National Science Foundation of China/ ; LGL-3142-ADB510100//Lingang Laboratory/ ; 2017QD081//the startup fund of Huashan Hospital, Fudan University/ ; 02220173//the crossing research project of Second Xiangya Hospital/ ; ynnkxyb202416//Brain science and brain-like research of Shanghai Sixth People's Hospital/ ; },
mesh = {Humans ; *Alzheimer Disease/pathology/metabolism ; *tau Proteins/metabolism ; Male ; Female ; *Bile Acids and Salts/metabolism ; Aged ; Biomarkers/metabolism ; *Amyloid beta-Peptides/metabolism ; Longitudinal Studies ; *Brain/pathology/metabolism ; Gastrointestinal Microbiome ; },
abstract = {INTRODUCTION: Alzheimer's disease (AD), a neurodegenerative disease, involves early alterations in the gut microbiota. Bile acids (BAs), which are metabolites produced by the microbiota, may impact brain function through the gut-brain axis.

METHODS: By reference to multimodal datasets from the Chinese Preclinical Alzheimer's Disease Study (n = 1397) and the Alzheimer's Disease Neuroimaging Initiative (n = 1275), we analyzed differences in BA levels and their associations with AD biomarkers.

RESULTS: Lithocholic acid (LCA) -family BAs are associated with the amyloid-β status. Longitudinal changes in BA levels correlated with amyloid and tau pathologies. LCA and the deoxycholic acid (DCA) family exhibited predictive value with respect to AD pathology. Imaging transcriptomic analyses suggested that BAs modulated amyloid pathology through multiple mechanisms.

DISCUSSION: DCA- and LCA-family BAs were proposed as molecular bridges that connect age signatures with AD pathology. They represent a new avenue for the development of biomarkers and therapeutic interventions.},
}

Humans
*Alzheimer Disease/pathology/metabolism
*tau Proteins/metabolism
Male
Female
*Bile Acids and Salts/metabolism
Aged
Biomarkers/metabolism
*Amyloid beta-Peptides/metabolism
Longitudinal Studies
*Brain/pathology/metabolism
Gastrointestinal Microbiome

@article {pmid41854052,
year = {2026},
author = {Labanda, MS and Noli Truant, S and Fernández, MM and Rosenbaum, E and Venturino, A and Capece, L},
title = {Polyamine Binding to Acetylcholinesterase Revealed by Molecular Dynamics and Surface Plasmon Resonance.},
journal = {Journal of chemical information and modeling},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jcim.6c00063},
pmid = {41854052},
issn = {1549-960X},
abstract = {Acetylcholinesterase (AChE) is a cholinergic enzyme that hydrolyzes acetylcholine to terminate neurotransmission. Inhibition of AChE prevents the breakdown of acetylcholine, leading to its accumulation and thereby providing therapeutic relief for memory deficits in Alzheimer's disease. While the inhibitory effects of synthetic ligands on AChE have been widely studied, the modulation of its activity by endogenous polyamines such as spermine and putrescine remains poorly understood at the molecular level. Previous kinetic studies have shown that polyamines can modulate AChE activity, exhibiting an inhibition effect at substrate concentrations less than ∼200 μM. In this work, we characterized the binding modes of polyamines to AChE using molecular dynamics simulations and binding free energy calculations, and measured the dissociation constants by surface plasmon resonance. Our results show that spermine and putrescine bind to the active-site gorge of AChE by interacting with residues of the peripheral anionic site, the catalytic site, and other important residues within the gorge. As a consequence, they block the pathway of the substrate toward the active site. This theoretical approach helps to understand the mechanism responsible for the inhibitory effects of polyamines on AChE activity observed experimentally.},
}

@article {pmid41854183,
year = {2026},
author = {Eagle, SR and Collins, M and Kontos, AP and Lopez, O and Mountz, JM and Wisniewski, SR and Edelman, K and Benso, S and Beers, S and Soose, RJ and Puccio, A and Rosario, B and Laymon, CM and Lopresti, B and Minhas, D and Agarwal, V and Okonkwo, DO},
title = {Utility of Amyloid Beta and Tau Positron Emission Tomography Scans for Identifying Early-Stage Neurodegenerative Changes in Former Professional Football Players and Healthy Controls: Results from the Brain Health Initiative.},
journal = {Journal of neurotrauma},
volume = {},
number = {},
pages = {8977151261433820},
doi = {10.1177/08977151261433820},
pmid = {41854183},
issn = {1557-9042},
abstract = {The aim of this study is to determine if there is a difference in tau and amyloid beta (Aβ) deposition on positron emission tomography (PET) scans between former players and controls, and if there is a differential association of the tau and Aβ deposition with concussion symptom burden. Participants completed the Rivermead Post-Concussion Questionnaire (RPQ) and PET imaging using Pittsburgh Compound B (PiB) and AV1451 ligands to identify uptake of Aβ and tau, respectively. Aβ standardized uptake value ratios (SUVR) and tau SUVR were compared between players and controls using a general linear model including age, race/ethnicity, years of education completed, and total number of prior sport-related traumatic brain injuries (TBIs) as covariates. A series of linear regression models were built to predict RPQ symptom scores including group status (player vs. control), Aβ SUVR and tau SUVR, and the interaction between group status and the Aβ SUVR and tau SUVR. Former players reported 4.9 ± 2.8 and control reported 1.4 ± 1.6 prior sport-related TBIs. Neither group reported any non-sport-related TBIs. Former players had higher RPQ symptom scores (13.3 ± 1.8) compared with controls (4.7 ± 1.8; p = 0.003). Controls had higher uptake for Aβ in the precuneus (1.22 ± 0.02) compared to players (1.14 ± 0.02; corrected p = 0.007). There were no differences between groups in uptake for Aβ in any other region of interest or tau in any region of interest. None of the regression models associating the interaction of group status and uptake with RPQ symptoms were significant. Aβ and tau PET scans may have limited utility for identifying potential neuropathological differences between participants with a career in professional football from controls who did not play football beyond high school. The PET tracer used for tau in the current study (AV1451) is well-suited for Alzheimer's disease-related tau pathology with limited binding for chronic traumatic encephalopathy-type tau proteins. A PET tracer for chronic traumatic encephalopathy-related tau deposition should remain a focus of future research.},
}