@article {pmid41742016,
year = {2026},
author = {Xu, F and Ren, J and Ma, J and Zhang, L and Qu, S and Zhang, W},
title = {Gut microbiota characteristics and its biological function analysis in patients with tuberculosis and diabetes mellitus co-morbidity.},
journal = {BMC microbiology},
volume = {26},
number = {1},
pages = {},
pmid = {41742016},
issn = {1471-2180},
support = {Z2023069//Jiangsu Municipal Health Commission/ ; YI2023023//Jiangsu Provincial Health Commission Scientific Researh Project/ ; QN2023042//Nantong Municipal Health Commission/ ; QNZ2025061//Nantong Municipal Health Commission/ ; ntly202408//the Sixth People's Hospital of Nantong/ ; },
abstract = {Tuberculosis and diabetes mellitus co-morbidity (TB_DM) poses harmful for human health and not conducive to early control. The gut microbiota has been proven to play an important role in a variety of diseases. In this study, we investigated the characteristics of the intestinal flora according to 16s rRNA sequencing results in their fecal samples in TB_DM, screened out independent bacterial genera to determine their diagnostic alone and in combination and explore their biological functions. A total 128 patients of 40 patients with diabetes mellitus (DM group), 40 patients with tuberculosis (TB group), 48 patients with TB_DM who met inclusion and exclusion criteria and 40 healthy persons as control group (HC group). We found that the sparse curves of the four groups were stable. The OTU analysis showed the most genus classification in the HC group and the least ones in the TB_DM group. Compared with the HC group, the α and β diversity were significantly decreased in the DM, TB and TB_DM group, particularly in TB_DM group. In the screening of independent genera, top 14 differential genera were found between the DM and the TB_DM group and top 18 ones between the TB and the TB_DM group.The top 3 bacterial genera Enterococcus, Flavonifractor and Romboutsia between DM and TB_DM groups were identified for analyzing diagnostic efficacy. The AUC, 95%CI, sensitivity and specificity were 0.742, 0.638 ~ 0.846, 64.58% and 80.00% in Enterococcus; 0.663, 0.547 ~ 0.779, 75.00% and 60.00% in Flavonifractor; 0.646, 0.530 ~ 0.762, 54.17% and 77.50% in Romboutsia and 0.835, 0.752 ~ 0.918, 79.17% and 75.00% in combined them, respectively. Also, the top 3 different genera Paeniclostridium, Dialister, and Lachnospira were found between TB and TB_DM groups for evaluating above diagnostic efficacy. The AUC, 95%CI, sensitivity and specificity were 0.716, 0.607 ~ 0.824, 81.25% and 57.50% in Paeniclostridium; 0.689, 0.575 ~ 0.803, 87.50% and 50.00% in Dialister; 0.672, 0.557–0.786, 83.33% and 55.00% in Lachnospira; and 0.914, 0.853 ~ 0.975, 85.42% and 85.00% in combined them, respectively. PICRUSt2 analysis indicated that differentially expressed genes (DEGs) predominantly influenced porphyrin and chlorophyll metabolism, pantothenate and CoA biosynthesis, as well as D-alanine metabolism between the DM and TB_DM groups. Furthermore, the DEGs were primarily associated with porphyrin and chlorophyll metabolism, Alzheimer’s disease and carotenoid biosynthesis when comparing the TB group to the TB_DM group. Our results provide key insights into the intestinal flora diversity, function and its independent genus in distinguishing TB_DM, TB and DM patients.},
}

@article {pmid41922909,
year = {2026},
author = {Dai, Q and Lin, Q and Chen, J and Deng, Z and Jin, W and Ye, P and Zuo, Y and Yang, Y and Xiao, S and Tang, Y},
title = {Prevalence and burden of neurological diseases in the Chinese mainland: An analysis from the Global Burden of Disease Study 2021.},
journal = {Chinese medical journal},
volume = {},
number = {},
pages = {},
pmid = {41922909},
issn = {2542-5641},
abstract = {BACKGROUND: Neurological diseases represent a growing challenge to the Chinese public health system. However, a comprehensive analysis of neurological diseases in China is lacking. This study aimed to analyze disease burden and risk factors of neurological diseases in the Chinese mainland to identify priorities for disease control and prevention.

METHODS: Disease burden and risk factors in the Chinese mainland were analyzed for 12 neurological disorders using data from the Global Burden of Diseases 2021 study and the Chinese Center for Disease Control and Prevention. Prevalence, deaths, years of life lost, years lived with disability (YLDs), and disability-adjusted life years (DALYs) were used as metrics.

RESULTS: Intracerebral hemorrhage (ICH) (1930.3 [95% uncertainty interval (UI): 1605.3-2296.7] per 100,000), ischemic stroke (1646.8 [95% UI: 1400.0-1893.1] per 100,000), Alzheimer's disease and other dementias (dementia) (708 [95% UI: 347.7-1561.7] per 100,000) made the greatest contributions to DALY rates in the Chinese mainland in 2021. The fastest growing contributors to DALY rates were dementia (208.2% [95% UI: 166.4-255.7%]), Parkinson's disease (160.7% [95% UI: 121.8-208.3%]), and ischemic stroke (95.2% [95% UI: 56.9-140.6%]). Migraine was the leading contributor to DALY rates among populations aged 10-39 years, ICH for those aged 40-74 years, ischemic stroke for those aged 75-89 years, and dementia for those aged >90 years. Ischemic stroke accounted for the highest age-standardized DALY rates in North and Northeast China, whereas ICH ranked first in other regions. High systolic blood pressure had the highest attributable DALYs for all diseases combined. Metabolic risk factors, alcohol use, secondhand smoke, and low physical activity contributed to higher YLDs in females, whereas alcohol use, smoking, and a high-sodium diet contributed to higher YLDs in males.

CONCLUSIONS: Neurological diseases present a growing public health challenge, characterized by significant disparities in their prevalence and presentation across age, sex, and geographic regions. Addressing these disparities requires coordinated strategies encompassing prevention, treatment, rehabilitation, and supportive care at the national level.},
}

@article {pmid41922938,
year = {2026},
author = {Yang, R and Wang, J and Dove, A and Sakakibara, S and Agarwal, P and Bennett, DA and Xu, W},
title = {Association of the Planetary Health Diet with dementia risk and brain pathology.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {4},
pages = {e71327},
pmid = {41922938},
issn = {1552-5279},
support = {82204142//National Natural Science Foundation of China/ ; 82501447//National Natural Science Foundation of China/ ; 2021KJ118//Science & Technology Development Fund of Tianjin Education Commission for Higher Education/ ; LA2025-0119//Lindhés Advokatbyrå AB/ ; 2025-02164//Stiftelsen för ålderssjukdomar/ ; FS-2025:0009//Loo och Hans Ostermans Foundation/ ; //Stiftelse för Medicinsk Forskning/ ; //Natural Science Foundation of Chongqing Municipality/ ; 2024-02959//Karolinska Institutet Research Foundation/ ; 2025-00707//Strategic Research Programm in Diabetes/ ; 2021-01826//The Swedish Research Council for Health Working Life and Welfare/ ; 2021-01647//The Swedish Research Council/ ; 2025-02364//The Swedish Research Council/ ; 2024-01820//Forte/ ; 2025-1031285//Demensfonden/ ; 2025-1030022//Alzheimerfonden/ ; R01AG17917/NH/NIH HHS/United States ; },
mesh = {Humans ; Male ; Female ; *Dementia/pathology/epidemiology ; Aged ; *Brain/pathology ; *Diet, Healthy ; *Alzheimer Disease/pathology/epidemiology ; Neuropsychological Tests ; Aged, 80 and over ; Risk Factors ; },
abstract = {BACKGROUND: The Planetary Health Diet (PHD), proposed by the EAT-Lancet Commission, promotes human and environmental health, yet its relevance to dementia and brain pathology remains unclear.

METHODS: In the Rush Memory and Aging Project, 926 dementia-free adults (mean age = 79.4) were followed for up to 20 years. Baseline diet was assessed using a >142-item food-frequency questionnaire, and PHD adherence was categorized into tertiles. Dementia and Alzheimer's dementia (AD) were clinically diagnosed. Among 581 decedents, brain autopsies quantified Alzheimer's disease, vascular, and other pathologies. Cognitive function proximate to death was measured via a standardized neuropsychological battery.

RESULTS: Over a median 7.5-year follow-up, 317 participants developed dementia. High PHD adherence was associated with lower risks of all-cause dementia (hazard ratio [HR] = 0.71) and AD (HR = 0.70), reduced Alzheimer's disease pathologies, a 2.17-year delay in dementia onset, and better end-of-life cognition.

CONCLUSION: High PHD adherence may support healthier brain aging and cognitive resilience.},
}

Humans
Male
Female
*Dementia/pathology/epidemiology
Aged
*Brain/pathology
*Diet, Healthy
*Alzheimer Disease/pathology/epidemiology
Neuropsychological Tests
Aged, 80 and over
Risk Factors

@article {pmid41922940,
year = {2026},
author = {Zheng, Y and Wu, X and Chen, H and Li, F and Yaffe, K and Stone, K and Leng, Y and Tan, X},
title = {Cyclic alternating pattern in sleep electroencephalography as a novel predictor of dementia: A prospective study.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {4},
pages = {e71331},
pmid = {41922940},
issn = {1552-5279},
support = {82570128//National Natural Science Foundation of China/ ; 2025C01119//Pioneer R&D Program of Zhejiang Province/ ; R01AG083836/AG/NIA NIH HHS/United States ; R21AG085495/AG/NIA NIH HHS/United States ; //National Institute on Aging (NIA)/ ; },
mesh = {Humans ; Male ; *Electroencephalography ; *Dementia/diagnosis/physiopathology ; Prospective Studies ; Aged ; *Sleep/physiology ; Aged, 80 and over ; Risk Factors ; },
abstract = {INTRODUCTION: Cyclic alternating pattern (CAP) is a sleep physiological rhythm observed during non-rapid eye movement (NREM) stage. However, the potential role of CAP for risk of dementia remains unknown.

METHODS: We studied 2,557 participants enrolled in the prospective Osteoporotic Fractures in Men (MrOS) Sleep Study. CAP features were calculated from electroencephalogram (EEG). The primary outcomes are probable dementia determined by physician diagnosis, Alzheimer's medication use, or a significant cognitive decline.

RESULTS: Participants in the lowest tertile of A2 index exhibited an increased risk of dementia compared to those in the highest tertile (hazard ratio [HR] = 2.00, 95% confidence interval [CI]: 1.38-2.90). Further, a lower combined A2+A3 index and shorter CAP sequence duration were associated with a higher risk of dementia. The Shapley Additive Explanations method indicates that CAP features were more predictive of dementia risk than conventional sleep parameters.

DISCUSSION: These findings suggest that specific CAP features may serve as useful predictors to identify those older men at risk of dementia.},
}

Humans
Male
*Electroencephalography
*Dementia/diagnosis/physiopathology
Prospective Studies
Aged
*Sleep/physiology
Aged, 80 and over
Risk Factors

@article {pmid41923110,
year = {2026},
author = {Natale, F and Dellaria, A and Nifo Sarrapochiello, I and Leone, L and Spinelli, M and Rinaudo, M and Garofalo, N and Grassi, C and Fusco, S},
title = {Intranasal administration of neural stem cell-derived extracellular vesicles prevents cognitive decline in both male and female 3×Tg-AD mice by dampening neuroinflammation and epigenetically regulating amyloid β metabolism.},
journal = {Alzheimer's research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13195-026-02014-7},
pmid = {41923110},
issn = {1758-9193},
support = {Ricerca Corrente//Ministero della Salute/ ; },
}

@article {pmid41923122,
year = {2026},
author = {Li, M and Cui, J and Qu, R and Liu, R and Sun, Y and Li, P and Liu, J and Low, A and Huang, X and Gan, F and Xu, ZZ},
title = {Porphyromonas gingivalis induces intestinal inflammation through gingipain-dependent gut microbiome dysbiosis.},
journal = {Microbiome},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40168-026-02389-7},
pmid = {41923122},
issn = {2049-2618},
support = {2025AHGXZK40069//Natural Science Foundation of Education Department of Anhui Province/ ; },
abstract = {BACKGROUND: Porphyromonas gingivalis (Pg), a key pathogen in periodontitis, is implicated in various systemic diseases such as pancreatic cancer and Alzheimer's disease. However, as a periodontal pathogen that can directly enter the lower gastrointestinal tract via saliva, its potential impact on the gut microbiome, intestinal inflammation, and its underlying mechanisms remains largely elusive.

RESULTS: Here, we observed that oral administration of Pg exacerbates intestinal inflammation in mice by inducing gut microbiome dysbiosis, increasing Th17 cells and the release of pro-inflammatory cytokines. Inhibition of Th17 activity with GSK805 or an anti-IL-17A blocking antibody mitigated this inflammatory response, highlighting the mediating role of Th17 cells. Gingipains, the virulence factors of Pg, played a crucial role in this process. Sequential knockout of gingipain genes revealed a gradual reduction in inflammatory phenotypes, with statistically significant alleviation observed when all three gingipain genes were deleted. Co-housing experiments showed that gut microbiota remodeling effectively protected against Th17-driven inflammatory response. Furthermore, immunization with inactivated Pg effectively prevented gut microbiome dysbiosis and Th17 cell-mediated inflammation.

CONCLUSION: Our findings suggest that Pg may exacerbate intestinal inflammation, potentially via its gingipain virulence proteases, which are linked to gut microbiota dysbiosis and enhanced Th17-mediated immune responses. These results suggest that gingipains could be promising targets for further investigation in Pg-associated intestinal disorders. Video Abstract.},
}

@article {pmid41923154,
year = {2026},
author = {Shimizu, A and Iwabuchi, Y and Bun, S and Watanabe, M and Kubota, M and Shimohama, S and Tezuka, T and Takahata, K and Tabuchi, H and Seki, M and Momota, Y and Yamamoto, Y and Shikimoto, R and Mimura, Y and Kurose, S and Sakurai, R and Takayama, T and Hoshino, Y and Hoshino, T and Suzuki, N and Morimoto, A and Osumi, A and Mimura, M and Jinzaki, M and Ito, D},
title = {Florzolotau (18F) retention is linked to neuropsychological performance in tauopathy.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {4},
pages = {e71319},
pmid = {41923154},
issn = {1552-5279},
support = {JP17pc0101006//Japan Agency for Medical Research and Development/ ; 16H06277//Japan Society for the Promotion of Science/ ; 17pc0101006//AMED to EISAI Co., Ltd/ ; },
mesh = {Humans ; Male ; Female ; *Tauopathies/diagnostic imaging/psychology/metabolism ; Neuropsychological Tests/statistics & numerical data ; Positron-Emission Tomography ; Aged ; *Alzheimer Disease/diagnostic imaging/psychology/metabolism ; *Cognitive Dysfunction/diagnostic imaging ; Middle Aged ; tau Proteins/metabolism ; *Brain/diagnostic imaging/metabolism ; Aged, 80 and over ; Fluorine Radioisotopes ; Carbolines ; },
abstract = {INTRODUCTION: Florzolotau (18F) positron emission tomography visualizes three- and four-repeat tau isoforms. We aimed to evaluate correlation of tau tracer retention with neuropsychological performance across the Alzheimer's disease (AD) continuum and non-AD tauopathies.

METHODS: This study enrolled 178 patients with cognitive impairment and 60 volunteers. Participants were divided into AD continuum (n = 120) and non-AD tauopathy (n = 98) groups and assessed using the Mini-Mental State Examination (MMSE), Clinical Dementia Rating, Functional Activity Questionnaire, Wechsler Memory Scale-Revised Logical Memory, Alzheimer's Disease Assessment Scale Cognitive subscale, Trail Making Test (TMT), word fluency, and the Japanese Adult Reading Test. Voxel-based analysis was performed.

RESULTS: In the AD continuum group, all cognitive test performances significantly correlated with tracer uptake, particularly in the left cortical areas. In the non-AD tauopathy group, strong correlations were observed with MMSE and TMT Part B performance.

DISCUSSION: Neuropsychological performance and regional tau pathology distribution are correlated in patients with tauopathy, with differences between AD continuum and non-AD tauopathy.

CLINICAL TRIAL REGISTRATION: This trial is registered with UMIN Clinical Trials (UMIN-CTR number: 000032027); submitted for registration on March 30, 2018; first patient enrolment was on July 3, 2018.},
}

Humans
Male
Female
*Tauopathies/diagnostic imaging/psychology/metabolism
Neuropsychological Tests/statistics & numerical data
Positron-Emission Tomography
Aged
*Alzheimer Disease/diagnostic imaging/psychology/metabolism
*Cognitive Dysfunction/diagnostic imaging
Middle Aged
tau Proteins/metabolism
*Brain/diagnostic imaging/metabolism
Aged, 80 and over
Fluorine Radioisotopes
Carbolines

@article {pmid41923420,
year = {2026},
author = {Luzzi, S and Snowden, JS},
title = {Low Sensitivity of Neuropsychological Scales Hinder Detection of Potential Benefit of Treatments in Alzheimer's Disease: A Position Paper.},
journal = {European journal of neurology},
volume = {33},
number = {4},
pages = {e70590},
pmid = {41923420},
issn = {1468-1331},
mesh = {Humans ; *Alzheimer Disease/diagnosis/drug therapy/psychology ; *Neuropsychological Tests/standards ; Cognitive Dysfunction/diagnosis ; Sensitivity and Specificity ; },
abstract = {BACKGROUND: Despite the advent of Disease Modifying Therapies (DMTs) for Alzheimer's Disease (AD), the approval and commercialization of anti-amyloid monoclonal antibodies has been slow and contentious, particularly in Europe. The primary source of debate is the discrepancy between robust biological effects-namely, effective β-amyloid clearance-and modest clinical improvements, which, although statistically significant, often fail to reach the minimal clinically important difference (MCID) compared to placebo.

METHODS: This paper highlights a confounding factor in the interpretation of the results of clinical trials: limited sensitivity of neuropsychological outcome measures. These tools, developed in the 1980s and only marginally updated, are not suited to detect subtle but meaningful cognitive changes in early disease stages.

RESULTS: The ADAS-Cog, the most commonly used cognitive endpoint, suffers from a substantial ceiling effect, impairing its ability to capture cognitive decline over short durations in prodromal populations. Likewise, functional scales such as the CDR-SB are inherently insensitive in mild cognitive impairment (MCI), as functional independence is, by definition, preserved. Moreover, the use of composite multidomain scales with high baseline scores may mask domain-specific improvements, further limiting a drug's capacity to reach MCID thresholds.

CONCLUSION: Methodological limitations risk undervaluing the therapeutic impact of treatment, particularly in trials targeting early or preclinical phases where changes are subtle and domain-specific. Urgent reconsideration of outcome measures is necessary to ensure accurate assessment of clinical efficacy and to avoid prematurely discarding potentially beneficial therapies.},
}

Humans
*Alzheimer Disease/diagnosis/drug therapy/psychology
*Neuropsychological Tests/standards
Cognitive Dysfunction/diagnosis
Sensitivity and Specificity

@article {pmid41923496,
year = {2026},
author = {Matthews, S and Nan, B},
title = {Regression for Left-Truncated and Right-Censored Data: A Semiparametric Sieve Likelihood Approach.},
journal = {Statistics in medicine},
volume = {45},
number = {8-9},
pages = {e70509},
doi = {10.1002/sim.70509},
pmid = {41923496},
issn = {1097-0258},
support = {RF1 AG075107/NH/NIH HHS/United States ; P30 AG066519/NH/NIH HHS/United States ; DMS 2412746//National Science Foundation/ ; },
mesh = {Humans ; Likelihood Functions ; Computer Simulation ; Linear Models ; Dementia ; Canada ; Cohort Studies ; Aged, 80 and over ; Data Interpretation, Statistical ; Bias ; Models, Statistical ; Regression Analysis ; },
abstract = {Cohort studies of the onset of a disease often encounter left-truncation on the event time of interest in addition to right-censoring due to variable enrollment times of study participants. Analysis of such event time data can be biased if left-truncation is not handled properly. We propose a semiparametric sieve likelihood approach for fitting a linear regression model to data where the response variable is subject to both left-truncation and right-censoring. We show that the estimators of regression coefficients are consistent, asymptotically normal and semiparametrically efficient. Extensive simulation studies show the effectiveness of the method across a wide variety of error distributions. We further illustrate the method by analyzing datasets from the Canadian Study of Health and Aging and The 90+ Study for aging and dementia.},
}

Humans
Likelihood Functions
Computer Simulation
Linear Models
Dementia
Canada
Cohort Studies
Aged, 80 and over
Data Interpretation, Statistical
Bias
Models, Statistical
Regression Analysis

@article {pmid41923871,
year = {2026},
author = {Wluka, VA and Despenza, T and Liu, AJ and Bramall, AN},
title = {Refining the diagnostic evaluation of idiopathic normal pressure hydrocephalus with Alzheimer's and α-synuclein biomarkers.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1736687},
pmid = {41923871},
issn = {1664-2295},
abstract = {Idiopathic normal pressure hydrocephalus (iNPH), characterized by ventriculomegaly and Hakim's triad of gait disturbance, cognitive impairment, and urinary dysfunction, is common in older adults. iNPH also remains one of the few potentially reversible neurological conditions, typically treated with cerebrospinal fluid (CSF) shunting. Although many patients improve, shunt responsiveness varies widely (≈60%-90%), and a subset of patients show only transient benefit. A major contributor to this variability is the high prevalence of comorbid neurodegenerative disease with symptom overlap, particularly Alzheimer's disease (AD) and α-synucleinopathies such as Parkinson's disease (PD) and dementia with Lewy bodies (DLB). The impact of these concomitant conditions on shunt outcomes, however, remains uncertain. We describe the incorporation of AD CSF biomarkers and α-synuclein skin biopsy into the iNPH evaluation to identify coexisting pathology. When integrated into routine workflow, approximately 32% of patients demonstrated AD-consistent CSF profiles and 31% had biopsy-confirmed α-synuclein pathology. We propose adopting concomitant neurological testing, especially in patients with atypical features to help inform patient selection and guide expectations. As the awareness and potential prevalence of iNPH rises and shunt procedures carry meaningful complication risks, delineating how comorbid disease modifies outcomes will be essential to improving the long-term success of shunting in iNPH.},
}

@article {pmid41923916,
year = {2026},
author = {Zhang, B and Hu, S and Li, H},
title = {Research progress and hotspots of the impact of Mediterranean diet on brain health from 2005 to 2025: a bibliometric and visualization analysis.},
journal = {Frontiers in nutrition},
volume = {13},
number = {},
pages = {1796774},
pmid = {41923916},
issn = {2296-861X},
abstract = {OBJECTIVE: To conduct bibliometric and visual analysis in the field of Mediterranean diet (MD) on brain health from 2005 to 2025.

METHODS: Relevant literature published between 2005 and 2025 was retrieved from the Web of Science and Scopus databases. R software and VOSviewer were used for data analysis and visualization.

RESULTS: The number of publications in this field showed a steady annual increase. The United States ranked first in terms of publication output, followed by Italy, Spain, China, and Australia. Notably, the United States also played a prominent role in international collaboration, with institutions such as Harvard University and the University of Barcelona actively cooperating with research centers worldwide. At the journal level, Nutrients emerged as the core academic platform in this field, ranking first in both the number of publications and citations. The study identified key researchers including Scarmeas N and Aggarwal NT. Major keywords included Alzheimer disease, dementia, gut microbiota, cognitive impairment, and oxidative stress, which reflect the central themes and research trends in MD and brain health.

CONCLUSION: As a healthy dietary therapy, the MD holds great promise for significant advances in the field of brain health. Growing global attention to this dietary pattern highlights its potential to become a core research direction in dietary interventions for brain disorders. This study provides a comprehensive analysis of the current research landscape and key hotspots of MD on brain health, offering valuable references for future investigations.},
}

@article {pmid41924004,
year = {2025},
author = {Krishnamurthy, S and Lu, L and Rudolph, M and Rundle, M and Sutphen, C and Register, TC and Leng, XI and Gaussoin, SA and Lipford, M and Ma, D and Caban-Holt, A and Byrd, GS and Baker, LD and Lockhart, SN and Craft, S and Bateman, JR and Hughes, TM},
title = {Associations of Place-based Social Determinants of Health with Biomarkers of Alzheimer's Disease and Related Dementias.},
journal = {Alzheimer's & dementia. Behavior & socioeconomics of aging},
volume = {1},
number = {4},
pages = {},
pmid = {41924004},
issn = {2997-3805},
abstract = {INTRODUCTION: Relationships between place-based social determinants of health (SDoH) and Alzheimer's disease and related dementias biomarkers are emerging.

METHODS: Linear regressions examined associations of area deprivation index (ADI), social vulnerability index (SVI), and environmental justice index (EJI) with biomarkers among Healthy Brain Study participants (n=679), stratified by racialized groups. Neuroimaging biomarkers included cortical thickness, brain parenchymal volume, white matter hyperintensity volume, cerebral blood flow (CBF) and its variability in gray matter. Plasma biomarkers included glial fibrillary acidic protein (GFAP), amyloid-beta ratios, and phosphorylated-tau 181.

RESULTS: Place-based SDoH measures were higher in Black compared to White participants. Among Black participants, we found relationships between higher SVI and EJI with higher CBF variability, higher ADI with lower mean CBF, and higher ADI and SVI with lower cortical thickness.

DISCUSSION: Place-based SDoH may partially capture effects of structural racism on brain health and affirm the importance of structural interventions in addressing SDoH.},
}

@article {pmid41924010,
year = {2026},
author = {Melgarejo, T and Harrison, S and Chang, Y and Munoz, M and Kim, M and Choi, Y and Riveroll-Gonzalez, JG and Natterson-Horowitz, B and Linde, A},
title = {Untargeted plasma metabolomics in canine cognitive dysfunction: the naturally occurring Alzheimer's disease analog in dogs.},
journal = {Frontiers in neuroscience},
volume = {20},
number = {},
pages = {1681817},
pmid = {41924010},
issn = {1662-4548},
abstract = {INTRODUCTION: Canine Cognitive Dysfunction (CCD) is an increasingly prevalent naturally occurring neurodegenerative condition in senescent dogs that share neuropathological and clinical features with human Alzheimer's disease (AD). Metabolic profiling allows for identification of new candidates for AD biomarkers, diagnostics, and therapeutics. Despite its translational potential, plasma metabolomic profiling of dogs with CDD has not been previously characterized.

METHODS: This case-control study analyzed plasma samples from ten client-owned geriatric dogs, including five with severe CCD and five age-matched, clinically healthy controls. Untargeted plasma metabolomics was performed using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Multivariate and univariate statistical analyses identified significant metabolic differences between the groups. Metabolites were considered significant based on a variable importance in projection (VIP) score > 1.5, fold change (FC) > 2.0, and adjusted p-value <0.05.

RESULTS: Fifteen metabolites across seven chemical classes were significantly altered in CCD dogs compared to controls, including glycerophospholipids, steroid derivatives, indoles, and mitochondrial-related compounds. Notably, elevated lysophosphatidic acid (LPA 20:2/0:0) and reduced ubiquinone-2 levels suggest dysregulation in neuroinflammatory and oxidative stress pathways. Cholesterol exhibited the highest FC and VIP scores, further reinforcing its role in AD pathogenesis. Hierarchical clustering and pathway enrichment analyses supported distinct metabolic signatures in CCD that mirror those observed in human AD.

DISCUSSION: This is the first untargeted plasma metabolomic profiling of dogs with CCD, revealing systemic metabolic disturbances that align with AD pathophysiology. Data was collected from senescent community-dwelling companion dogs, which enhances the study's ecological and translational relevance. It supports the utility of CCD as an AD model and highlight candidate plasma biomarkers that warrant further investigation. Future longitudinal studies integrating metabolomics with neuroimaging, histopathology, and behavioral assessments are required to validate these findings and contribute to AD biomarker discovery and therapeutic development.},
}

@article {pmid41924228,
year = {2026},
author = {Dalla Costa, L and Meneghello, F and Righetto, C and Senes, G},
title = {Farm-based therapeutic horticulture for people living with dementia: the Vicenza Farm Project.},
journal = {Frontiers in dementia},
volume = {5},
number = {},
pages = {1772835},
pmid = {41924228},
issn = {2813-3919},
abstract = {Dementia is a major global health challenge, with wide-ranging psychosocial and relational impacts that call for supportive, everyday interventions alongside clinical care. While advances in Alzheimer's disease are promising, dementia includes multiple conditions, including young-onset forms, and existing pharmacological and non-pharmacological interventions still offer valuable but incomplete support, often leaving everyday psychosocial needs unmet for most people living with dementia. This Perspective describes the Vicenza Farm Project, a farm-based therapeutic horticulture program developed on social and educational farms of Northern Italy. The program offers weekly 3-h group sessions from March to October for around 8-10 participants, including people with young-onset dementia, facilitated by a multidisciplinary team of farmers, psychologists and trained volunteers. Activities follow a structured, replicable protocol that combines cognitive stimulation, seasonal gardening and farm tasks, shared breaks and closing reflection, with an emphasis on supported participation, personal agency and safe freedom. Drawing on qualitative and quantitative data from international literature on nature-based and care farming interventions, we outline how a farm-based therapeutic horticulture can help restore purpose, social connection and embodied identity while also animating rural spaces and reinforcing environmentally sensitive farming practices. We contrast the Italian policy framework of social agriculture, in which therapeutic horticulture is not yet recognized as a health intervention, with the more institutionalized Dutch model of green care farms, and we propose priorities for evaluation, integration into dementia pathways and long-term funding.},
}

@article {pmid41924410,
year = {2026},
author = {Khan, Z and Jafri, M and Lambroussis, CG},
title = {Incarcerated Ventral Hernia Requiring Emergent Repair in an Adult With Down Syndrome: Diagnostic and Postoperative Challenges in an Underrepresented Population.},
journal = {Cureus},
volume = {18},
number = {2},
pages = {e104459},
pmid = {41924410},
issn = {2168-8184},
abstract = {The manifestation of ventral hernias is quite common, with an increased risk of progressing to incarceration/strangulation, which imposes the need for emergent surgery. Patients with Down syndrome (DS) present unique anatomical, physiological, and neurodevelopmental characteristics that may complicate diagnosis and postoperative management. In general, DS has been well studied for perioperative risk primarily with pediatric and cardiac populations, yet emergency general surgical outcomes in adults remain poorly studied. In our case report, a 59-year-old woman with DS and Alzheimer's disease underwent emergent robotic ventral hernia repair for an incarcerated ventral hernia. Her postoperative course was complicated by several features, including obstipation, urinary retention with bilateral hydronephrosis, and the development of bilateral segmental and subsegmental pulmonary emboli on postoperative day four. Interventions for these complications, such as a Foley catheter insertion for urinary retention, led to additional complications. Diagnosis and management were primarily guided by physical examination and cross-sectional imaging, given the patient's limited ability to provide a reliable clinical history. Our case report highlights the challenges of standard postoperative care in adults with DS and also stresses the importance of personalized monitoring, diagnostic imaging, and multidisciplinary approaches, especially for individuals with complex disease processes.},
}

@article {pmid41924560,
year = {2025},
author = {Sinha, A and Jaiswal, N and Jadiya, P and Tomar, D},
title = {Mitochondrial connection to Alzheimer's disease and heart failure.},
journal = {Current opinion in physiology},
volume = {44},
number = {},
pages = {},
pmid = {41924560},
issn = {2468-8673},
abstract = {The brain and heart are intricately linked, with dysfunction in one organ often affecting the other. Cardiovascular diseases (CVDs), particularly heart failure, impair cerebral blood flow, contributing to cognitive decline and increasing dementia risk. Conversely, Alzheimer's disease (AD), marked by amyloid-beta plaques and tau tangles, impacts cardiac function. A shared mechanism between AD and CVDs is mitochondrial dysfunction, which disrupts energy production and oxidative balance, worsening both neurodegeneration and heart health. This interdependence underscores the potential for mitochondria-targeted therapies to address both conditions. With an aging population facing rising incidences of AD and CVDs, understanding these interconnected pathways and the central role of mitochondria could inform new therapeutic strategies and improve outcomes in both neurodegenerative and cardiovascular diseases.},
}

@article {pmid41924697,
year = {2026},
author = {Coito, A and Brügger, D and Brémovà-Ertl, T and Massatsch, P and Abegg, M and Weber, KP and Salmen, A},
title = {Advances in ocular motor and pupil biomarkers for neurological disorders.},
journal = {Brain communications},
volume = {8},
number = {2},
pages = {fcag102},
pmid = {41924697},
issn = {2632-1297},
abstract = {Neurological disorders are often difficult to diagnose and monitor, particularly in the early stages when symptoms may be subtle or nonspecific. Because the visual system engages a large portion of the cerebral cortex and relies on well-defined neural pathways, it offers a unique and accessible window into brain function. In this context, the concepts of oculomics and oculometrics have gained increasing attention. Oculomics refers to the study of systemic and neurological diseases through ocular biomarkers, while oculometrics involves the computational quantification of eye and pupil parameters. Together, these approaches provide noninvasive, objective, and reproducible methods to assess neurological function, with strong potential to improve diagnostic precision, monitor disease progression, and guide individualized care. This review synthesizes recent advances in ocular motor and pupillary biomarkers in three major neurological conditions: multiple sclerosis, Parkinson's disease, and Alzheimer's disease. In multiple sclerosis, early ocular motor disturbances such as internuclear ophthalmoplegia, saccadic dysmetria, and impaired smooth pursuit are frequently observed and may reflect brainstem and cerebellar involvement. Relative afferent pupillary defect, objectively measured with pupillometry, is a strong indicator of optic neuritis. In Parkinson's disease, impaired saccadic initiation, hypometric saccades, and convergence abnormalities reflect basal ganglia dysfunction, while pupil irregularities suggest underlying autonomic imbalance. In Alzheimer's disease, impairments in saccades, smooth pursuit, fixation instability, and the pupillary light reflex have been associated with early cortical and brainstem pathology, reflecting deficits in attention, executive control, and cholinergic function. We also discuss the integration of eye-tracking data with neuroimaging and electrophysiology biomarkers to support multimodal diagnostic frameworks with the potential to improve diagnostic accuracy and disease monitoring. In addition, we highlight how recent technological developments in virtual reality-based eye-tracking could offer immersive, standardized testing conditions to enable scalable implementation of oculometric assessments in clinical practice. As the fields of oculomics and oculometrics continue to evolve, these approaches hold promise to bridge the gap between research and clinical application. However, large-scale validation studies, standardized protocols, and normative datasets are essential for broader clinical adoption. By embedding ocular motor and pupillary biomarkers into routine neurological assessments, clinicians may be able to detect disease earlier, differentiate between overlapping syndromes, and monitor therapeutic outcomes more effectively.},
}

@article {pmid41924730,
year = {2026},
author = {Pan, T and Liu, Z},
title = {Lactylation omics of rabbit rotator cuff tear reveals differentially modified proteins and metabolic relating therapy targets.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1797466},
pmid = {41924730},
issn = {2296-858X},
abstract = {Proteins exert biological functions not only depending on abundance but also on regulation. Lactylation, a novel post-translational modification, can mediate metabolic reprogramming and epigenetic regulation, playing a crucial role in signal transduction, gene expression and cellular metabolism. Lactylation is also involved in various diseases, such as tumors, Alzheimer's disease, heart failure and myocardial infarction. However, there is little research in musculoskeletal system. In this study, we conducted lactylation omics on rabbit rotator cuff tear samples and identified 2,624 modification sites on 851 proteins. We obtained results on subcellular localization, differentially modified proteins and functional pathway enrichment. Basing on motif, we proposed the "lysine co-lactylation modification effect" concept. Overall, lactylation mainly localized in cytoplasm, mitochondria and nucleus, with its functions enriching in RNA processing, DNA processing and cellular metabolism. Considering that lactylation is widely present and significantly occurs in rotator cuff tears, we aim to identify the key targets through which lactylation exerts its effects and to intervene it, ultimately providing new insights and therapeutic approaches for clinic therapy.},
}

@article {pmid41924789,
year = {2026},
author = {Muhtar, MS and Chirakalwasan, N and Chiu, HY and Pongpitakmetha, T and Hsu, MH and Chen, PY and Al-Nouman, H and Thato, R and Hasan, F},
title = {Post-stroke insomnia and the risk of post-stroke cognitive impairment and dementia: A large retrospective cohort study.},
journal = {Sleep medicine},
volume = {143},
number = {},
pages = {108929},
doi = {10.1016/j.sleep.2026.108929},
pmid = {41924789},
issn = {1878-5506},
abstract = {To evaluate the association between post-stroke insomnia (PSI) and the incidence of post-stroke cognitive impairment (PSCI), dementia, and all-cause mortality compared to stroke survivors without insomnia. We analyzed electronic health record data from the TriNetX Global Collaborative Network (119 healthcare organizations). Adults diagnosed with stroke between January 1, 2004, and September 30, 2017, were included. Patients with pre-existing insomnia were excluded. Patients were categorized as having PSI if diagnosed with insomnia after the index stroke, or as a non-insomnia comparator if no sleep disorder was recorded. Propensity score matching was used to balance baseline characteristics. The primary outcome was PSCI. Secondary outcomes included all-cause dementia, Alzheimer's disease, and all-cause mortality. Cox proportional hazard models were used to estimate hazard ratios (HRs) with 95% CIs. After propensity score matching, 35,144 patients were included in each cohort (PSI and non-insomnia). During follow-up, patients with PSI had significantly higher risks of PSCI (HR, 1.29; 95% CI, 1.24-1.34), all-cause dementia (HR, 1.30; 95% CI, 1.23-1.37), and Alzheimer's disease (HR, 1.28; 95% CI, 1.13-1.45) compared to the non-insomnia group. The risk of all-cause mortality was not different between the groups. Multivariable Cox model analyses revealed stronger associations of PSI with PSCI, dementia, and Alzheimer's disease in older adults, females, and those with diabetes, musculoskeletal diseases, hypertensive diseases, digestive disorders, specific head injuries, antidepressant use, NSAID use, and non-opioid analgesics use. In this large cohort study, PSI was associated with a significantly increased risk of cognitive decline, including PSCI, dementia, and Alzheimer's disease. These findings suggest that systematic screening and management of insomnia should be integrated into post-stroke care pathways to potentially mitigate long-term cognitive deterioration.},
}

@article {pmid41924834,
year = {2026},
author = {Zhang, H and Yan, H},
title = {Comment on "Modeling inter-slice dependencies with temporal graph learning for Alzheimer's disease".},
journal = {Journal of the neurological sciences},
volume = {485},
number = {},
pages = {125890},
doi = {10.1016/j.jns.2026.125890},
pmid = {41924834},
issn = {1878-5883},
}

@article {pmid41924980,
year = {2026},
author = {Chaulagain, B and Gothwal, A and Mahanta, AK and Jarajapu, YPR and Singh, J},
title = {Cannabidiol and pBDNF Cotreatment Attenuates Pathological Symptoms and Improves Cognition in 3 month-Old 5XFAD Mice.},
journal = {ACS chemical neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1021/acschemneuro.5c01009},
pmid = {41924980},
issn = {1948-7193},
abstract = {The marginal efficiency observed with the existing therapies in Alzheimer's Disease (AD) can be attributed to the timing of the treatment. The beneficiaries of symptomatic or disease-modifying therapy for AD are mild-cognitive-impairment (MCI) or late-stage dementia patients. At this stage, the pathological features are already advanced and irreversible, as the shift in biomarker levels starts in a continuum 15-20 years prior. Early intervention, therefore, is a plausible solution to this issue. Consequently, we selected 3 month-old 5XFAD AD mice as an early intervention model. We administered cannabidiol (CBD) and plasmid brain-derived neurotrophic factor (BDNF) encapsulated in liposome nanoparticles, functionalized with penetratin and mannose for brain-targeting, as a therapy. Neuroinflammation is emerging as a key driver of AD progression by its interaction with amyloid plaques and phosphorylated tau. Therefore, CBD, which is anti-inflammatory and neuroprotective, was used. BDNF, a synaptic modulation and cognitive maintenance agent, is declined and, thus, aggravates pathology and cognition in AD. BDNF expressed from the liposome nanoparticles supplements the reduced BDNF and aids in ameliorating AD pathology. We found four weekly doses of our formulation reduced the amyloid burden by 3.04-fold (p-value < 0.0001), declined pro-inflammatory cytokines TNF-α by 2.51-fold (p-value < 0.0001), IL-1β by 2.34-fold (p-value < 0.0001) and microglial activation by 2.15-fold (p-value < 0.0001) than saline controls. In addition, it increased the synaptic markers level and promoted adult hippocampal neurogenesis, eventually improving cognitive functions. These findings suggest the use of CBD and pBDNF has a potential therapeutic combination for AD management if intervened early.},
}

@article {pmid41925063,
year = {2026},
author = {Shtilbans, A and Lang, AE},
title = {Combination Disease-Modifying Therapy for Neurodegenerative Diseases Using Repurposed Drugs.},
journal = {Annals of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ana.78190},
pmid = {41925063},
issn = {1531-8249},
abstract = {We review the positive effects of several existing drugs from different classes, such as chemical chaperones, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), iron chelators, and cluster-Abelson tyrosine kinase inhibitors (c-Abl TKIs), in preclinical disease models and in available published human data following use of these drugs in individuals with common neurodegenerative diseases (NDs), including Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). A concept of combinatory neuroprotective therapy using a drug-repurposing approach is then discussed. Finally, we propose a strategy to design an ideal combination of drugs able to address multiple pathogenic processes involved in neurodegeneration to achieve clinically meaningful results. ANN NEUROL 2026 ANN NEUROL 2026.},
}

@article {pmid41925140,
year = {2026},
author = {Liu, X and Citu, C and Qu, G and Liu, W and Enduru, N and Liu, A and Tung, CH and Zhao, Z},
title = {BDCD: a comprehensive Brain Disease Cell-cell communication Database.},
journal = {Database : the journal of biological databases and curation},
volume = {2026},
number = {},
pages = {},
doi = {10.1093/database/baag017},
pmid = {41925140},
issn = {1758-0463},
support = {U01AG079847/NH/NIH HHS/United States ; R01LM012806/NH/NIH HHS/United States ; RP240610//Cancer Prevention and Research Institute of Texas/ ; RP210045//Genomics, and Translational Cancer Research Training Program/ ; T32ES027801//Training in Precision Environmental Health Sciences/ ; },
mesh = {Humans ; *Cell Communication/genetics ; *Brain Diseases/genetics/pathology/metabolism ; *Databases, Genetic ; Transcriptome ; },
abstract = {Dysregulated cell-cell communication (CCC) is increasingly recognized as a driver of brain disease pathology, contributing to neuroinflammation, synaptic dysfunction, and neurodegeneration. Nevertheless, existing resources remain limited in brain specificity, regional coverage, and functional annotation. To address this gap, we develop the Brain Disease Cell-cell communication Database (BDCD), the first comprehensive resource focused on CCC networks across major brain diseases. BDCD integrates 38 manually curated datasets, comprising 8 519 425 single cells from single-cell RNA-seq studies and 140 744 spots from spatial transcriptomic maps, spanning 14 brain regions and 13 canonical cell types covering Alzheimer's disease, Parkinson's disease, schizophrenia, bipolar disorder, and multiple sclerosis. BDCD reconstructs more than 495 000 ligand-receptor interaction events and links them to structural features, genetic associations, pathways, and therapeutic modulators, including 6100 single nucleotide polymorphisms from genome-wide association studies, 3350 drugs, and 72 477 allosteric modulators. This comprehensive atlas enables cross-disease comparison and supports dynamic hypothesis generation, providing a foundation for mechanistic insights and therapeutic discovery. BDCD is publicly available at https://bioinfo.uth.edu/bdcd/. Database URL: https://bioinfo.uth.edu/bdcd/.},
}

Humans
*Cell Communication/genetics
*Brain Diseases/genetics/pathology/metabolism
*Databases, Genetic
Transcriptome

@article {pmid41925203,
year = {2026},
author = {Viola, G and Sperotto, A and Palmioli, A and Tira, R and Munari, F and Assfalg, M and Airoldi, C and D'Onofrio, M},
title = {Cinnamon Bud Extract Is a Source of Biomolecules Active against the Aggregation and Condensation of Alzheimer's-Associated Tau Protein.},
journal = {Journal of agricultural and food chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jafc.5c17659},
pmid = {41925203},
issn = {1520-5118},
abstract = {Abnormal accumulation of tau fibrillar aggregates is a hallmark of tauopathies, including Alzheimer's disease. Targeting tau aggregation represents a promising strategy for preventing and treating neurological disorders, especially using natural compounds with favorable safety profiles. In this study, we investigated a hydroalcoholic extract of Cinnamomum cassia buds (BCHE) and its major components, cinnamaldehyde and shikimic acid, for their effects in modulating tau repeat domain aggregation and liquid-liquid phase separation. In vitro results show that BCHE and cinnamaldehyde inhibit tau aggregate maturation, promoting the formation of nonfibrillar, off-pathway species and modulating condensate formation. These alternative aggregates exhibit reduced cytotoxicity in SH-SY5Y neuroblastoma cells and lower seeding capacity than canonical fibrils. BCHE also contains compounds capable of binding preformed tau fibrils. Overall, these findings suggest a novel mechanism by which cinnamon-derived bioactive molecules mitigate tau aggregation and reduce its cellular toxicity, highlighting their potential as neuroprotective agents.},
}

@article {pmid41925207,
year = {2026},
author = {Liu, S and Huang, J and Calderon, R and Spira, AP and Mcphillips, MV and Goonertne, N and Gill, J and Li, J},
title = {Sleep architecture and self-reported sleep quality are associated with Alzheimer's disease biomarkers in older adults without dementia.},
journal = {The journals of gerontology. Series A, Biological sciences and medical sciences},
volume = {},
number = {},
pages = {},
doi = {10.1093/gerona/glag081},
pmid = {41925207},
issn = {1758-535X},
abstract = {BACKGROUND: Sleep disruption is common in older adults and is a significant risk factor for developing Alzheimer's disease (AD). This study examines the association between self-reported sleep quality, actigraphy- and electroencephalogram (EEG)-measured sleep parameters, and plasma amyloid-tau-neurodegeneration (ATN) biomarkers in older adults without dementia.

METHODS: We analyzed baseline data from a randomized controlled trial of 103 sedentary community-dwelling older adults with insomnia symptoms but without dementia. Participants completed the Pittsburgh Sleep Quality Index (PSQI) and wrist actigraphy, provided blood samples for plasma biomarkers assays (amyloid-beta [Aβ] 42, Aβ40, Aβ42/40 ratio, total tau, and neurofilament light [NfL]), and a subsample (n = 56) underwent two-night ambulatory EEG. Multiple regression models tested associations between sleep measures and plasma ATN biomarkers.

RESULTS: Participants averaged 70.0 ± 6.0 years old, and 80.6% were female. Adjusted analyses showed greater rapid eye movement (REM) sleep percentage was associated with lower Aβ40 (β = -0.018; 95% confidence interval [CI] = -0.027, -0.010) and higher Aβ42/40 ratio (β  =  0.016; 95% CI = 0.007, 0.025). Higher PSQI scores were nominally associated with higher Aβ42 (β  =  0.017, 95% CI = 0.004, 0.031) and NfL (β  =  0.034, 95% CI = 0.007, 0.062), but these associations did not sustain false discovery rate correction.

CONCLUSIONS: Greater REM sleep was associated with a more favorable plasma amyloid profile, whereas associations between subjective sleep quality and plasma biomarkers were nominal and require confirmation in larger studies. These findings suggest that REM sleep architecture measured using ambulatory EEG may be particularly sensitive to amyloid-related changes prior to dementia.},
}

@article {pmid41925474,
year = {2026},
author = {Alfonso-Triguero, M and Arranz, AM},
title = {Reprogramming aging astrocytes in Alzheimer's disease.},
journal = {Trends in neurosciences},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.tins.2026.03.002},
pmid = {41925474},
issn = {1878-108X},
abstract = {Alzheimer's disease typically unfolds within an aging brain, where astrocytic transcriptional programs are extensively remodeled. A recent study by Choi and colleagues shows that reinstating an aging-dependent Sox9 (SRY-box transcription factor 9)-MEGF10 (multiple EGF-like domains 10) axis restores amyloid clearance and preserves cognition in mouse models. These findings suggest that astrocyte dysfunction reflects destabilized, yet recoverable, homeostatic programs rather than irreversible degeneration.},
}

@article {pmid41925793,
year = {2026},
author = {Ramanan, S and Johnson, GVW},
title = {A Bioinformatic Analysis of BAG Protein Interactors and Pathways in Alzheimer's and Parkinson's Disease.},
journal = {Journal of molecular neuroscience : MN},
volume = {76},
number = {2},
pages = {},
pmid = {41925793},
issn = {1559-1166},
support = {R01AG073121/GF/NIH HHS/United States ; },
mesh = {Humans ; *Parkinson Disease/metabolism/genetics ; *Alzheimer Disease/metabolism/genetics ; *Transcription Factors/metabolism/genetics ; Computational Biology ; *DNA-Binding Proteins/metabolism/genetics ; Animals ; *Adaptor Proteins, Signal Transducing/metabolism/genetics ; Signal Transduction ; *Apoptosis Regulatory Proteins/metabolism/genetics ; },
abstract = {Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most common neurodegenerative disorders. Within the scope of neurodegenerative disorders, the Bcl-2 associated athanogene (BAG) family proteins and associated interactors have been a key area of focus. The BAG family is a group of proteins that contain at least one evolutionarily conserved BAG domain. Despite this similarity, their interactions and functions can vary widely. So far, research has predominantly scrutinized individual BAG proteins, rather than explore potential cooperative actions among family members. Some BAG family members may function together thereby indicating potential interactions within this family. Although connections among BAG members have been observed, their role in neurodegenerative disorders, such as AD and PD, remains largely uncharacterized. This mini review explores the common pathways, intersections, and differences within these interactions as well as their link to AD and PD. Using computational techniques to mine transcriptomic data, several groupings of pathways that these BAG family members are involved in were identified in the context of AD and PD. Understanding these pathways and their relationships may uncover potential gaps in current research and help identify novel therapeutic targets for the treatment of these neurodegenerative diseases.},
}

Humans
*Parkinson Disease/metabolism/genetics
*Alzheimer Disease/metabolism/genetics
*Transcription Factors/metabolism/genetics
Computational Biology
*DNA-Binding Proteins/metabolism/genetics
Animals
*Adaptor Proteins, Signal Transducing/metabolism/genetics
Signal Transduction
*Apoptosis Regulatory Proteins/metabolism/genetics

@article {pmid41925933,
year = {2026},
author = {Ali, NH and Al-Kuraishy, HM and Hussain, NR and Al-Gareeb, AI and Albuhadily, AK and Waheeb, TS and Batiha, GE},
title = {Repurposing of doxycycline as a novel therapeutic avenue for management of parkinson's disease.},
journal = {Inflammopharmacology},
volume = {},
number = {},
pages = {},
pmid = {41925933},
issn = {1568-5608},
abstract = {Parkinson's disease (PD) is the second most common neurodegenerative disease subsequent to Alzheimers disease (AD). PD is characterized by progressive neurodegeneration of the dopaminergic neurons in the substantia nigra pars compacta (SNpc). Notably, the management of PD is chiefly symptomatic without modifying the underlying PD neuropathology. Moreover, prolonged use of anti-PD medications may be correlated with severe harmful effects such as dyskinesia and neuronal oxidative stress. Consequently, repurposing FDA-permitted therapies with antioxidants and anti-inflammatory capacities may prevent the progression of PD neuropathology. The antibiotic doxycycline has been shown to alleviate PD neuropathology by restraining the development of neurodegeneration, neuroinflammation, oxidative stress, and endoplasmic reticulum (ER) stress. However, the molecular mechanism of doxycycline in PD is not fully explained. Hence, this review purposes to examine the various effects of doxycycline regarding its potential molecular mechanism alongside the progression of PD.},
}

@article {pmid41925947,
year = {2026},
author = {Patwekar, F and Patwekar, M and Wei, LS and Sharma, R and Varghese, R and Mohammed, A},
title = {Advancing diagnostic biomarkers in Alzheimer's disease: interdisciplinary innovations and technological frontiers.},
journal = {Human cell},
volume = {39},
number = {4},
pages = {},
pmid = {41925947},
issn = {1749-0774},
mesh = {*Alzheimer Disease/diagnosis/metabolism/genetics ; Humans ; *Biomarkers/metabolism ; Biosensing Techniques ; Machine Learning ; tau Proteins ; Nanotechnology ; Precision Medicine ; *Inventions/trends ; Positron-Emission Tomography ; *Interdisciplinary Research ; Magnetic Resonance Imaging ; Amyloid beta-Peptides ; Early Diagnosis ; Artificial Intelligence ; },
abstract = {Developing diagnostic biomarkers for Alzheimer's disease (AD) is at the cutting edge of interdisciplinary research and technical advancement. This comprehensive analysis investigates potential options for improving diagnostic accuracy and early detection of AD. Identifying biomarkers other than Aβ and tau proteins, such as synaptic dysfunction markers and metabolic indicators, is a novel technique. Integrating multi-omics data provides a comprehensive picture of AD pathophysiology, assisting in the discovery of biomarkers and treatment targets. Advances in technology, notably nanotechnology and biosensors, show promise for highly sensitive and specific platforms capable of identifying AD-related biomarkers in physiological fluids. AI and machine learning algorithms are critical in analyzing large datasets, improving pattern identification, and increasing diagnostic accuracy. Predictive models based on various biomarkers and clinical data open the way for personalized medicine methods in the treatment of AD. More advancements in PET and MRI tracers are required for targeted and sensitive imaging of specific AD-related clinical alterations. Wearing gadgets and seeing digital health signs have helped us to find diseases early and track them over time. They even allow monitoring from afar and all the time. This comprehensive review brings together new developments and teamwork across different fields. In this way, it guides to enhance how to identify AD. By mixing these new methods, we aim to change the diagnosis of AD early and accurately. This allows us to focus on treatments and push forward new cures for AD.},
}

*Alzheimer Disease/diagnosis/metabolism/genetics
Humans
*Biomarkers/metabolism
Biosensing Techniques
Machine Learning
tau Proteins
Nanotechnology
Precision Medicine
*Inventions/trends
Positron-Emission Tomography
*Interdisciplinary Research
Magnetic Resonance Imaging
Amyloid beta-Peptides
Early Diagnosis
Artificial Intelligence

@article {pmid41925951,
year = {2026},
author = {Feng, JQ and Yang, LL and Luo, YX and Yao, XQ},
title = {Alzheimer's disease: from molecular pathways to therapies.},
journal = {Molecular biomedicine},
volume = {7},
number = {1},
pages = {},
pmid = {41925951},
issn = {2662-8651},
support = {No.82371427//National Natural Science Foundation of China/ ; No.82401656//National Natural Science Foundation of China/ ; CSTB2023NSCQ-MSX0323//Natural Science Foundation of Chongqing Municipality/ ; 2025MSXM044//Joint project of Chongqing Health Commission and Science and Technology Bureau/ ; CYB240199//Postgraduate Research and Project of Chongqing Province/ ; },
mesh = {*Alzheimer Disease/therapy/metabolism/pathology/etiology ; Humans ; Amyloid beta-Peptides/metabolism ; tau Proteins/metabolism ; Animals ; Immunotherapy/methods ; Gastrointestinal Microbiome ; Signal Transduction ; },
abstract = {Alzheimer disease (AD) is the most common neurodegenerative disorder and a leading cause of dementia worldwide. With accelerating population aging, its incidence continues to rise, imposing a substantial burden on public health systems and society. Despite extensive advances in research, currently available therapies remain largely symptomatic and have limited capacity to halt or reverse disease progression. Recent progress in understanding the molecular and cellular mechanisms underlying AD has driven the development of targeted therapeutic strategies, particularly immunotherapies directed against amyloid-β (Aβ) and tau pathology. However, the pathogenesis of AD is highly complex and multifactorial, underscoring the need for a more integrated understanding of the interactions among diverse pathological processes and the identification of additional therapeutic targets. Here, we provide a systematic synthesis of the core pathological mechanisms of AD and their interconnected molecular pathways, together with a comprehensive overview of current targeted therapeutic strategies. We highlight recent advances in Aβ- and tau-directed immunotherapies and further examine emerging interventions targeting neuroinflammation, metabolic dysregulation, the gut microbiota, lifestyle-related factors, and neurogenesis, evaluating their potential based on evidence from both clinical and preclinical studies. By integrating mechanistic insights with therapeutic developments, this review outlines key opportunities and challenges in the evolving landscape of AD treatment. These perspectives may inform the development of next-generation disease-modifying therapies and contribute to a more comprehensive framework for understanding the pathogenesis and treatment of AD.},
}

*Alzheimer Disease/therapy/metabolism/pathology/etiology
Humans
Amyloid beta-Peptides/metabolism
tau Proteins/metabolism
Animals
Immunotherapy/methods
Gastrointestinal Microbiome
Signal Transduction

@article {pmid41926104,
year = {2026},
author = {Devanand, DP and Wei, R and Qian, M},
title = {Treatment of Early Symptomatic Alzheimer Disease With Valacyclovir-Reply.},
journal = {JAMA},
volume = {},
number = {},
pages = {},
doi = {10.1001/jama.2026.1105},
pmid = {41926104},
issn = {1538-3598},
}

@article {pmid41926105,
year = {2026},
author = {Kosaka, M and Kami, M},
title = {Treatment of Early Symptomatic Alzheimer Disease With Valacyclovir.},
journal = {JAMA},
volume = {},
number = {},
pages = {},
doi = {10.1001/jama.2026.1102},
pmid = {41926105},
issn = {1538-3598},
}

@article {pmid41926304,
year = {2026},
author = {Senwar, KR and Dhillon, A and Yadav, M},
title = {Small Molecule Inhibitors Targeting Pathogenic Protein Aggregation in Neurodegenerative Diseases: Medicinal Chemistry and Mechanistic Insights.},
journal = {Current topics in medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115680266439510260223082224},
pmid = {41926304},
issn = {1873-4294},
abstract = {A hallmark of Neurodegenerative Diseases (NDs) is protein misfolding, aggregation, and accumulation in specific brain regions. The accumulation of insoluble, misfolded protein aggregates is usually referred to as amyloid formation. This process leads to cellular dysfunction, destruction of neurons, loss of neuronal connections in specific brain areas, and brain damage. Despite the involvement of distinct pathogenic proteins, the underlying mechanisms of misfolding and aggregate formation are remarkably similar across various NDs. In this review, we present a comprehensive overview of the medicinal chemistry and mechanistic insights into phytochemicals and synthetic small molecules with potential for the treatment of neurodegenerative disorders. Various small molecules have been reported to have therapeutic effects by inhibiting the misfolding, aggregation, and accumulation of pathogenic proteins, such as amyloid-β, tau, and α- synuclein. This review mainly covers natural product-derived small molecules, notably polyphenols (including flavonoids and non-flavonoid polyphenols), as well as other phytochemical classes, such as quinones and alkaloids, along with their possible mechanisms of action. In addition, synthetic small molecules, osmolytes, metal chelators, and repurposed drugs for neurodegenerative disorders are thoroughly discussed.},
}

@article {pmid41926311,
year = {2026},
author = {Khan, AH and Ubaid, B and Perry, G},
title = {Reconciling Divergent Perspectives: A Deep Analysis of Sex Differences in Alzheimer's Disease Mortality Data.},
journal = {Current Alzheimer research},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115672050450797260211050217},
pmid = {41926311},
issn = {1875-5828},
}

@article {pmid41926312,
year = {2026},
author = {Mehrabadi, S},
title = {Investigating the Potential of Gene Editing Technologies in Enhancing Stem Cell Therapy for Alzheimer's Disease.},
journal = {Current aging science},
volume = {},
number = {},
pages = {},
doi = {10.2174/0118746098414335251203135400},
pmid = {41926312},
issn = {1874-6128},
abstract = {Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by progressive cognitive decline and memory loss, significantly affecting the quality of life for millions of people worldwide. Current therapeutic options primarily focus on symptomatic relief, with limited effectiveness in addressing the underlying pathophysiology. Recent advancements in gene editing technologies, particularly CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats), offer promising opportunities to enhance stem cell therapy for AD. This review explores the potential of gene editing to target genetic risk factors associated with AD, such as APOE4 (Apolipoprotein E) and TREM2 (Triggering Receptor Expressed on Myeloid Cells 2), and to improve the differentiation and functionality of induced pluripotent stem cells (iPSCs) derived from AD patients. By creating more accurate disease models and humanized animal systems, researchers can gain a deeper understanding of the mechanisms of AD and evaluate novel therapeutic strategies. Moreover, combining gene editing with stem cell therapy may facilitate cell replacement therapies and the development of exosome-based treatments that modulate neuroinflammation and promote neuroprotection. Despite the promise of these approaches, challenges, such as off-target effects, delivery efficiency, and ethical considerations, remain significant hurdles. This review aims to provide a comprehensive overview of the current state of research, emphasizing the potential of gene editing technologies to revolutionize stem cell therapy for AD and improve patient outcomes.},
}

@article {pmid41926576,
year = {2026},
author = {Smith, JE},
title = {Scientists brace for expansion of Alzheimer's blood tests.},
journal = {Science (New York, N.Y.)},
volume = {392},
number = {6793},
pages = {14-15},
doi = {10.1126/science.aeh6877},
pmid = {41926576},
issn = {1095-9203},
mesh = {*Alzheimer Disease/blood/diagnosis ; Humans ; *tau Proteins/blood ; Biomarkers/blood ; Phosphorylation ; },
abstract = {Growing use of p-tau217 raises concerns about testing in healthy people.},
}

*Alzheimer Disease/blood/diagnosis
Humans
*tau Proteins/blood
Biomarkers/blood
Phosphorylation

@article {pmid41926581,
year = {2026},
author = {Reineke, LC and Zhu, PJ and Dalwadi, U and Dooling, SW and Liu, Y and Wang, IC and Young-Baird, S and Okoh, J and Kuncha, SK and Zhou, H and Kannan, A and Park, H and Debeaubien, NA and Croll, T and Lee, DJ and Arthur, C and Dever, TE and Walter, P and Chen, J and Frost, A and Costa-Mattioli, M},
title = {Harnessing viral strategies to reverse cognitive dysfunction through the integrated stress response.},
journal = {Science (New York, N.Y.)},
volume = {392},
number = {6793},
pages = {eaea8782},
doi = {10.1126/science.aea8782},
pmid = {41926581},
issn = {1095-9203},
mesh = {Animals ; Mice ; *Cognitive Dysfunction/genetics/therapy ; *Protein Phosphatase 1/genetics/metabolism ; Neuronal Plasticity ; Disease Models, Animal ; Alzheimer Disease/genetics/therapy ; Down Syndrome/genetics/therapy ; *Stress, Physiological/genetics ; Humans ; Cognition ; Memory, Long-Term ; Aging ; Male ; Protein Biosynthesis ; },
abstract = {The integrated stress response (ISR) is essential for cellular homeostasis and cognitive function. We investigated how persistent ISR activation affects cognitive performance by studying the PPP1R15B[R658C] genetic variant associated with intellectual disability. To model this condition, we generated a mouse line with the pathogenic allele inserted. This variant destabilized the PPP1R15B•PP1 phosphatase complex, causing persistent ISR activation, impaired protein synthesis, and long-term memory deficits. We demonstrated that the cognitive and synaptic impairments in Ppp1r15b[R658C] mice arise directly from ISR activation. Furthermore, we characterized DP71L, a viral ortholog of PPP1R15B, which acted as a potent pan-ISR inhibitor. DP71L reversed the cognitive and synaptic deficits across mouse models of Down syndrome, Alzheimer's disease, and aging, and enhanced synaptic plasticity and memory in healthy mice.},
}

Animals
Mice
*Cognitive Dysfunction/genetics/therapy
*Protein Phosphatase 1/genetics/metabolism
Neuronal Plasticity
Disease Models, Animal
Alzheimer Disease/genetics/therapy
Down Syndrome/genetics/therapy
*Stress, Physiological/genetics
Humans
Cognition
Memory, Long-Term
Aging
Male
Protein Biosynthesis

@article {pmid41926749,
year = {2026},
author = {Oh, Y and Palanikumar, L and Howarth, M and Maity, D and Ali, L and Mustafa, M and Kumar, S and Hamilton, AD and Magzoub, M},
title = {Prion Protein-Derived Cell-Penetrating Peptide Inhibits Type II Diabetes-Associated Islet Amyloid Polypeptide Aggregation and Cytotoxicity.},
journal = {Biochemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.biochem.5c00634},
pmid = {41926749},
issn = {1520-4995},
abstract = {Islet amyloid polypeptide (IAPP) is a 37-residue peptide hormone copackaged and cosecreted with insulin by pancreatic β-cells. A pathological hallmark of type II diabetes is the self-assembly of IAPP into β-sheet rich amyloid fibers, which is associated with β-cell impairment. Previously, we showed that a cell-penetrating peptide (CPP) construct, consisting of a hydrophobic signal sequence coupled to a polycationic nuclear localization signal (NLS)-like sequence, exhibited potent antiprion activity and antagonism of Alzheimer's disease-associated amyloid-β (Aβ) peptide aggregation and neurotoxicity. Here, we have extended this approach toward type II diabetes by assessing the efficacy of the CPP construct, designated as neural cell adhesion molecule-1 (NCAM1)-prion protein (PrP), in inhibiting IAPP oligomerization, fiber formation, and associated cytotoxicity. Using complementary in vitro and in silico experiments, we show that NCAM1-PrP effectively modulates IAPP's toxic structures into nontoxic conformations. This study underlines the potential of our designed CPP-based therapeutic approach as a versatile tool in the battle against amyloid-associated pathologies.},
}

@article {pmid41926822,
year = {2026},
author = {Dos Santos, JMM and de Moura, AB and Medeiros, EB and Generoso, CM and Tietboh, LTW and Lidio, AV and Steiner, BT and Scussel, R and Dal-Bó, AG and Budni, J and Machado-de-Ávila, RA},
title = {A novel synthetic peptide impairs spatial working memory in mice: A promising tool for dementia-related neurotoxicity animal models studies.},
journal = {Neuropeptides},
volume = {117},
number = {},
pages = {102609},
doi = {10.1016/j.npep.2026.102609},
pmid = {41926822},
issn = {1532-2785},
abstract = {The rapid aging of the global population is contributing to a sharp increase in dementia cases, with Alzheimer's disease (AD) accounting for the majority of diagnoses. The most widely accepted theory explaining AD pathogenesis is the amyloid cascade hypothesis, which implicates the accumulation of amyloid-β (Aβ) peptides, particularly the Aβ1-42 isoform, as a key pathogenic event. Oligomeric forms of Aβ1-42 act as bioactive neurotoxic peptides, disrupting synaptic function and neuronal homeostasis. Despite its frequent use in animal models, Aβ1-42 presents challenges due to its high cost and complex handling. In this study, we applied bioinformatic and structural approaches to identify a minimal peptide motif within Aβ1-42 capable of reproducing its neurobiological effects. We designed and evaluated the peptide fragment Aβ16-21 (KLVFFA), which corresponds to the hydropHobic core of Aβ1-42 and is a critical determinant of peptide aggregation and bioactivity. We assessed the cognitive and biochemical effects of intracerebroventricular administration of Aβ16-21 in mice and compared its impact to that of Aβ1-42. Behavioral testing revealed significant deficits in both working and reference memory in animals treated with either Aβ1-42 or Aβ16-21, with no clear dose-dependent effects. Biochemical evaluation demonstrated increased levels of the anti-inflammatory cytokine IL-10 in the cortex and hippocampus after Aβ16-21 administration, while TNF-α levels remained unchanged, indicating peptide-dependent modulation of neuroimmune responses. Notably, Aβ16-21 consistently formed neurotoxic oligomeric assemblies despite its reduced length. These findings demonstrate that Aβ16-21 retains key neurotoxic and immunomodulatory properties of full-length Aβ1-42, supporting its use as a biologically relevant minimal neuroactive peptide. Due to its structural simplicity, reproducibility, lower cost, and experimental accessibility, Aβ16-21 represents a valuable peptide-based tool for modeling AD-related neuropeptide dysfunction in preclinical research.},
}

@article {pmid41926844,
year = {2026},
author = {Beyrer, J and Sheff, Z and Payakachat, N and Chandler, JM and Chen, YF and Kubisiak, J and Lee, A and Holdridge, KC and Yaari, R and Aisen, P and Rafii, MS and Sperling, RA and , },
title = {Increase in healthcare utilization and Medicare payment with progression of preclinical Alzheimer's disease.},
journal = {The journal of prevention of Alzheimer's disease},
volume = {13},
number = {6},
pages = {100547},
doi = {10.1016/j.tjpad.2026.100547},
pmid = {41926844},
issn = {2426-0266},
abstract = {BACKGROUND: Alzheimer's disease (AD) begins with the preclinical stage (Stages 1 and 2) where individuals are cognitively unimpaired but have AD pathology. Healthcare utilization and medical cost of cognitively unimpaired (preclinical) AD have not been previously evaluated.

OBJECTIVES: To describe healthcare resource utilization (HRU) and Medicare payments among cognitively unimpaired individuals with and without elevated amyloid and to evaluate the association of AD progression with HRU and Medicare payments.

DESIGN: Retrospective cohort analysis of the randomized controlled trial (Anti-Amyloid Treatment in Asymptomatic AD [A4]) and companion observational study (Longitudinal Evaluation of Amyloid Risk and Neurodegeneration [LEARN]) linked with Medicare.

SETTING: Clinical trials sites in the United States PARTICIPANTS: 246 cparticipants with cognitively unimpaired AD in A4 and 121 amyloid-negative participants in LEARN Medicare cohorts.

MEASUREMENTS: Measures from Medicare claims included medical conditions (diagnosis codes), HRU (inpatient, emergency room, outpatient, professional, skilled nursing facility, home health), and Medicare payments. AD progression (or cognitive or functional decline) was measured using Clinical Dementia Rating Scale-Global Score (CDR-GS) in A4/LEARN and diagnosis codes for cognitive impairment, AD, and JEN Frailty Index (JFI) of ≥6 (high frailty) in Medicare data.

RESULTS: HRU and payments were overall similar between A4 and LEARN Medicare. Claims indicators suggesting AD progression in A4 Medicare were associated with higher inpatient, outpatient, emergency room, and home health utilization (any utilization) and increased number of inpatient stays. Payments were significantly greater in A4 Medicare with AD progression vs without progression: 45% payment increase for cognitive impairment (p=0.035) with a mean incremental cost of $140 per person per month (PPPM) (95% confidence interval [CI] $125-$155), 66% payment increase for AD (p=0.011) with a mean incremental cost of $207 PPPM (95% CI $188-$226), and 103% payment increase for high frailty (p<0.001) with a mean incremental cost of $303 PPPM (95% CI $283-$323).

CONCLUSIONS: Overall, individuals with cognitively unimpaired AD in A4 Medicare did not have increased utilization and payments vs LEARN. HRU and payments were significantly greater in A4 Medicare participants with AD progression indicators in claims vs those without progression. These results highlight the need for additional research on both health and economic impacts of progression in a real-world (routine care) cohort of individuals with cognitively unimpaired AD and the potential cost savings associated with effective therapy that delays AD progression in cognitively unimpaired AD.

NCT02008357, NCT02488720.},
}

@article {pmid41927108,
year = {2026},
author = {Zhang, P and Xie, J and Liu, L and Zheng, Y and Yang, Y},
title = {Asiaticoside Alleviates Alzheimer's Disease by Regulating PPP1CC Expression to Suppress Inflammation and Mitochondrial Dysfunction.},
journal = {Annals of clinical and laboratory science},
volume = {56},
number = {1},
pages = {51-59},
pmid = {41927108},
issn = {1550-8080},
mesh = {*Alzheimer Disease/drug therapy/metabolism ; Humans ; *Mitochondria/drug effects/metabolism ; *Triterpenes/pharmacology ; Apoptosis/drug effects ; *Inflammation/drug therapy/metabolism ; Cell Survival/drug effects ; Membrane Potential, Mitochondrial/drug effects ; Amyloid beta-Peptides/metabolism ; Interleukin-1beta/metabolism ; },
abstract = {OBJECTIVE: Alzheimer's disease (AD) is a neurodegenerative disorder. Asiaticoside (AS), one of the main active components of Centella asiatica, shows therapeutic potential in various diseases, including AD. However, the specific molecular mechanisms by which AS treats AD remain unclear.

METHODS: Cell counting kit-8 (CCK-8) and flow cytometry were used to assess cell viability, apoptosis, and changes in JC-1 mitochondrial membrane potential. Western blot (WB) was used to detect protein expression. The ferrous ion fluorescence assay kit was used to measure Fe[2+] levels. Enzyme-linked immunosorbent assay (ELISA) kits were used to detect interleukin-1β (IL-1β) and IL-6 levels. GeneCards, comparative toxicogenomics database (CTD), and swisstargetprediction databases were used to obtain AD and AS targets. Enrichment analysis and plotting were performed using the clusterProfiler package in R. The simplified molecular input line entry system (SMILES) website was used to obtain the 3D structure of AS. The universal protein resource (UniProt) website was used to obtain the protein structure of protein phosphatase 1 catalytic subunit gamma (PPP1CC). Autodock v4.2.6 was used for molecular docking.

RESULTS: AS improved cell viability in amyloid β1-42 (Aβ1-42)-induced human brain microvascular endothelial cells (HBMECs), reduced apoptosis, reduced Fe[2+], IL-1β, and IL-6 levels, restored the JC-1 mitochondrial membrane potential, and increased the expression of glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11). Analysis identified six overlapping genes between AS and AD. Gene ontology (GO) functional annotation of these genes showed significant enrichment in response to hypoxia, neuron differentiation, and mitochondrial function. Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis revealed significant enrichment in tumor necrosis factor (TNF) signaling pathway, IL-17 signaling pathway, and others. Molecular docking demonstrated that AS could stably bind to the PPP1CC protein. Further experiments showed that PPP1CC knockdown exerted regulatory effects on Aβ1-42-induced HBMECs similar to those exerted by AS, whereas PPP1CC overexpression produced the opposite effects.

CONCLUSION: AS protects Aβ1-42-induced HBMECs, likely through modulating PPP1CC expression.},
}

*Alzheimer Disease/drug therapy/metabolism
Humans
*Mitochondria/drug effects/metabolism
*Triterpenes/pharmacology
Apoptosis/drug effects
*Inflammation/drug therapy/metabolism
Cell Survival/drug effects
Membrane Potential, Mitochondrial/drug effects
Amyloid beta-Peptides/metabolism
Interleukin-1beta/metabolism

@article {pmid41927258,
year = {2026},
author = {Bertin-Hugault, F},
title = {[Paro the seal, a tool for helping the elderly].},
journal = {Revue de l'infirmiere},
volume = {75},
number = {319},
pages = {32-33},
doi = {10.1016/j.revinf.2026.02.011},
pmid = {41927258},
issn = {1293-8505},
mesh = {Humans ; Aged ; *Robotics/instrumentation ; },
abstract = {Paro is a robot provided to healthcare staff to assist people with cognitive impairments, communication difficulties, or multiple disabilities. It truly forms a trio: caregiver, patient, and Paro. The team's motivation is essential.},
}

Humans
Aged
*Robotics/instrumentation

@article {pmid41927280,
year = {2026},
author = {Giarratana, AO and Jonaitis, E and Przybelski, RJ and Cody, K and Betthauser, TJ and Cadman, R and Alberson, SF and Christian, BT and Johnson, SC},
title = {Longitudinal Evaluation of [18]F-MK-6240 Along the Alzheimer Disease Continuum.},
journal = {Journal of nuclear medicine : official publication, Society of Nuclear Medicine},
volume = {},
number = {},
pages = {},
doi = {10.2967/jnumed.125.271127},
pmid = {41927280},
issn = {1535-5667},
abstract = {Understanding the rate of tau accumulation is critical for staging Alzheimer disease (AD), monitoring its progression, and informing clinical trial design. Although PET imaging with [18]F-MK-6240, also known as florquinitau, can track tau pathology, longitudinal data remain limited. We evaluated longitudinal tau changes using [18]F-MK-6240 PET across cognitive stages and analyzed regional rates of change with the goal of informing future clinical trial outcome measures. Methods: In this observational study, 27 participants with varying cognitive statuses (cognitively unimpaired [CU], mild cognitive impairment [MCI], and AD) underwent [18]F-MK-6240 PET at baseline and at 6, 12, and 24 mo (or at 18 and 30 mo during the COVID-19 pandemic). Amyloid positivity at baseline was determined with [11]C-labeled Pittsburgh compound B PET. Tau PET data were analyzed as SUV ratios (SUVRs) in regions of interest (ROIs) corresponding to Braak staging as well as the inferior temporal gyrus and 2 composite ROIs (metatemporal composite [MTC]) and an early tau composite. Annualized SUVR changes were compared across groups and correlated with cognitive scores (Mini-Mental State Examination, Clinical Dementia Rating Scale, and the Alzheimer's Disease Assessment Scale-Cognitive Subscale) using the Kruskal-Wallis test. Correlations between the change in SUVR and cognitive outcomes were estimated using Spearman ρ. Results: Baseline [18]F-MK-6240 PET showed a minimal signal in CU participants, localized signal to the medial temporal lobe in participants with MCI, and a signal spanning the inferolateral temporal lobe and extending posteriorly along the ventral cortex in participants with AD. Longitudinal analysis showed that the annualized percent change in tau deposition in the MTC was 0.17% ± 4.16, 5.77% ± 2.97, and 4.31% ± 5.84 in the CU, MCI, and AD groups, respectively (P = 0.075). The change in tau deposition was 0.00 ± 0.05, 0.10 ± 0.07, and 0.12 ± 0.16 in the CU, MCI, and AD groups, respectively (P = 0.039). Tau accumulation correlated with a decline on the Alzheimer Disease Assessment Scale-Cognitive Subscale (ρ = 0.43, P < 0.05). Conclusion: [18]F-MK-6240 PET tracked tau accumulation over time and provided preliminary evidence that these changes correlate with cognitive decline, supporting its utility for longitudinal AD studies and trial design, with MTC emerging as a promising ROI for clinical trials.},
}

@article {pmid41927413,
year = {2026},
author = {Pesce, G and Estivill-Alonso, M and Ventura, S},
title = {Programmable CAR immunotherapies for neurodegenerative proteinopathies.},
journal = {Trends in pharmacological sciences},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.tips.2026.02.009},
pmid = {41927413},
issn = {1873-3735},
abstract = {Abnormal protein aggregation and a dysregulated neuroimmune environment are defining features of many neurodegenerative disorders. In Alzheimer's disease, systemic monoclonal antibodies against amyloid-β provide proof of principle that immunotherapy can modify disease trajectory. However, clinical benefit is limited by low brain exposure, short-lived activity, the need for repeated dosing, and inflammation-linked toxicity. Building on transformative clinical success in oncology, chimeric antigen receptor (CAR) immunotherapies offer a complementary approach to address these limitations, combining the molecular precision of antibody-derived binders with the versatility and persistence of engineered immune cells. These technologies are being explored for central nervous system (CNS) proteinopathies, where they can couple the selective recognition of pathogenic proteoforms to immune programs that are compatible with the CNS's low tolerance for collateral inflammation. Here, we review CAR strategies for aggregate-selective targeting and explore how to incorporate tunable controls and safety mechanisms. Finally, we examine how distinct CAR-engineered effector cell types may modulate key processes in neurodegeneration, from aggregate clearance to immune rebalancing. Together, these advances define CAR design principles for durable, programmable, and targeted immunomodulation in neurodegenerative disease.},
}

@article {pmid41927485,
year = {2026},
author = {Yuka, SA and Telli, K and Yılmaz, A},
title = {In Silico Structure-Guided Design of Peptide Candidates Targeting γ-Secretase Subunit Assembly.},
journal = {Proteins},
volume = {},
number = {},
pages = {},
doi = {10.1002/prot.70137},
pmid = {41927485},
issn = {1097-0134},
abstract = {The γ-secretase complex is a membrane-embedded protease essential for intramembrane cleavage of substrates such as Notch receptors and the amyloid precursor protein (APP), processes central to cancer progression and Alzheimer's disease (AD) pathology. However, catalytic inhibition of γ-secretase disrupts multiple signaling pathways, resulting in dose-limiting toxicities. In this study, we report a structure-guided approach to generate peptides with binding and stability profiles that disrupt the assembly of γ-secretase by targeting the interactions of Presenilin-1 and Nicastrin with APH1. First, molecular docking was performed for 36 248 peptides of varying lengths to assess their affinity scores to the PS1 and NCT interaction regions of APH1. Peptides filtered based on their affinity scores and physicochemical properties were then subjected to global molecular docking. 50-nanosecond molecular dynamics simulations and MM/PBSA analyses were performed on the top 10 potential candidates, identifying those with high dynamic interaction potential. Thus, seven γ-secretase inhibitor candidates with favorable affinity scores capable of providing stable interactions and thereby having the potential to disrupt the APH1:PS1 assembly were identified. This approach, which overcomes the challenges of targeting the transmembrane catalytic domain, is based on the inhibition of subunit assembly and presents promising candidates for future experimental studies.},
}

@article {pmid41708330,
year = {2026},
author = {Lessard, CB and Rubio Rubio, D and Tolton, S and Criado-Marrero, M and Ravi, S and Garza, TN and Koren, J and Philips, J and Bagchi, P and McFarland, K and Chhangani, D and Golde, TE and Giasson, BI and Lewis, J and Chakrabarty, P and LaVoie, MJ and Borchelt, DR and Seyfried, NT and Prokop, S and Rincon-Limas, DE and Abisambra, JF},
title = {Progressive Supranuclear Palsy PERK Haplotype B Selectively Translates DLX1 Promoting Tau Toxicity.},
journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
volume = {46},
number = {13},
pages = {},
doi = {10.1523/JNEUROSCI.1727-25.2026},
pmid = {41708330},
issn = {1529-2401},
support = {R01 AG077534/AG/NIA NIH HHS/United States ; },
mesh = {Humans ; *Supranuclear Palsy, Progressive/genetics/metabolism/pathology ; *Transcription Factors/genetics/metabolism ; Male ; Female ; *tau Proteins/toxicity/metabolism/genetics ; *Homeodomain Proteins/genetics/metabolism ; Animals ; Haplotypes/genetics ; *eIF-2 Kinase/genetics/metabolism ; Unfolded Protein Response/genetics ; Tauopathies/genetics/metabolism ; },
abstract = {The unfolded protein response (UPR) sensor PERK exists in haplotypes A and B. PERK-B confers increased risk for tauopathies like progressive supranuclear palsy (PSP), but the mechanisms distinguishing its function from PERK-A and contributing to its association with tauopathy remain unknown. Here, we developed a controlled cellular model for a pair-wise comparison of the two PERK haplotypes, finding their UPR functions nearly indistinguishable. Puromycin-based proteomics highlighted a subset of mRNA translation events that was permissible under the PERK-B-dependent, but not the PERK-A-dependent, UPR. One of the targets that escaped PERK-B suppression was the transcription factor DLX1, which is genetically linked to PSP risk. We found that DLX1 solubility shifted to a detergent-insoluble fraction in the human brain tissue from male and female PSP donors. Furthermore, silencing the fly homolog of DLX1 was sufficient to decrease tau-induced toxicity in vivo. Our results detail the haplotype-specific PERK-B/DLX-1 pathway as a novel driver of tau pathology in cells, flies, and likely the human brain, revealing new insights into PSP pathogenesis and potential therapeutic targets.},
}

Humans
*Supranuclear Palsy, Progressive/genetics/metabolism/pathology
*Transcription Factors/genetics/metabolism
Male
Female
*tau Proteins/toxicity/metabolism/genetics
*Homeodomain Proteins/genetics/metabolism
Animals
Haplotypes/genetics
*eIF-2 Kinase/genetics/metabolism
Unfolded Protein Response/genetics
Tauopathies/genetics/metabolism

@article {pmid41903899,
year = {2026},
author = {Green, MC and Braun, DJ and Leibold, CT and Van Eldik, LJ and Bailey, CS},
title = {Specific inhibition of p38α MAPK dampens neuroinflammation during acute alcohol withdrawal in mouse BV2 microglial cell line and rat organotypic hippocampal slice cultures.},
journal = {Alcohol (Fayetteville, N.Y.)},
volume = {133},
number = {},
pages = {32-37},
doi = {10.1016/j.alcohol.2026.03.007},
pmid = {41903899},
issn = {1873-6823},
abstract = {Neuroinflammation is implicated in anxiety and negative affect in alcohol withdrawal, potentially contributing to relapse. The mitogen-activated protein kinase p38α (p38) is a critical driver of neuroinflammation in such excitatory neural contexts, and its inhibition reduces neuroinflammatory cytokine production in the context of various insults generally corresponding with improved cellular and synaptic health. Although heretofore unexamined, we hypothesized that inhibition of p38 by small-molecule MW150 would reduce neuroinflammation during the acute alcohol withdrawal period. Immortalized mouse BV2 and post-natal day 8 rat organotypic hippocampal slice cultures received 50mM ethanol in media for 24 h followed by 24 h withdrawal, or for 48 h continuously, with administration of 5 μM MW150 or saline for the final 24 h of treatment. Control tissue never received ethanol. Levels of cytokines in the culture media were analyzed after 48 h by MesoScale ELISA assays. Elevated CXCL1 and TNFα levels were ameliorated by MW150 during ethanol withdrawal in culture media from BV2 and female OHSC, respectively. Further, MW150 reduced TNFα, but increased IL6, across all conditions in the BV2 microglia. Preliminary evidence suggests that p38 inhibition during early ethanol withdrawal in vitro reduces select inflammatory cytokines. Given that MW150 is presently in clinical trials for neuroinflammation in Alzheimer's disease, its preclinical validation for use in alcohol withdrawal in vivo is crucial to determine its feasibility to modulate neuroinflammation and problem drinking in humans.},
}

@article {pmid41917398,
year = {2026},
author = {Nadanaka, S and Kitagawa, H},
title = {Sulfated Glycosaminoglycans in Inflammation.},
journal = {Advances in experimental medicine and biology},
volume = {1491},
number = {},
pages = {221-231},
pmid = {41917398},
issn = {0065-2598},
mesh = {Humans ; *Inflammation/metabolism/pathology/immunology ; *Glycosaminoglycans/metabolism ; Animals ; Proteoglycans/metabolism ; Aging/metabolism ; },
abstract = {Inflammation has long been regarded as a tissue repair mechanism activated by the body in response to infection or tissue injury. In recent years, chronic inflammation has been implicated as a proinflammatory factor not only in various diseases, such as cancer, atherosclerosis, obesity, and Alzheimer's disease, which increase with age, but also in the aging process itself. What mechanisms cause the inflammatory response that normally dissipates, persists, and becomes chronic? Elucidating the factors that cause chronic inflammation and the mechanisms that induce it will provide insights into the prevention and control of various age-related diseases. In this review, we focus on proteoglycans as factors that cause chronic inflammation and discuss proteoglycans as DAMPs that cause inflammation.},
}

Humans
*Inflammation/metabolism/pathology/immunology
*Glycosaminoglycans/metabolism
Animals
Proteoglycans/metabolism
Aging/metabolism

@article {pmid41917443,
year = {2026},
author = {O'Leary, K},
title = {GLP-1 receptor agonist fails to halt Alzheimer's disease.},
journal = {Nature medicine},
volume = {},
number = {},
pages = {},
doi = {10.1038/d41591-026-00018-2},
pmid = {41917443},
issn = {1546-170X},
}

@article {pmid41917601,
year = {2026},
author = {Kurz, CI and Perneczky, R and Tegethoff, P and Hufnagel, A},
title = {[The new Alzheimer's blood tests].},
journal = {MMW Fortschritte der Medizin},
volume = {168},
number = {6},
pages = {48-54},
doi = {10.1007/s15006-026-5711-7},
pmid = {41917601},
issn = {1613-3560},
}

@article {pmid41917677,
year = {2026},
author = {van Maanen, E and Gonçalves, A and Chen, L and Fauchet, F and Cristea, S and Smith, J and Baddeley, T and Shiells, H and Hewitt, F and Schelter, BO and Wischik, CM},
title = {Atypical population pharmacokinetics of hydromethylthionine in patients with Alzheimer's disease explains unexpected phase 3 trial results.},
journal = {British journal of clinical pharmacology},
volume = {},
number = {},
pages = {},
doi = {10.1002/bcp.70539},
pmid = {41917677},
issn = {1365-2125},
support = {//TauRx Pharmaceuticals/ ; },
abstract = {AIM: Tau aggregation contributes to the pathology of Alzheimer's disease (AD). Tau aggregation inhibitors (TAI) are potential disease-modifying drugs for AD and other tauopathies. Hydromethylthionine (HMT) is a potent orally administered TAI, which also has tau-independent symptomatic activity. The purpose of this analysis was to characterize HMT pharmacokinetics (PK) in healthy volunteers and AD patients.

METHODS: Data from five Phase I studies and the TRx-237-039 Phase 3 study (mild to moderate AD and mild cognitive impairment) were combined, including single doses of hydromethylthionine mesylate (HMTM) (4-100 mg), multiple dose regimens (8-80 mg/day) and long-term data (16 mg/day) over a maximum of 104 weeks. In TRx-237-039, methylthioninium chloride (MTC, 4 mg twice weekly), which also delivers HMT, was intended to maintain blinding for urine discoloration without therapeutic activity based on linear PK modelling of earlier trial data. The PK model characterized active HMT, regardless of its source. Plasma HMT data from 710 participants with 7784 measurements were analysed using non-linear mixed effects modelling.

RESULTS: The model described inter-individual variability, time-varying (U-shaped) clearance, and the impact of clinically relevant covariates on the PK. The U-shaped clearance over 24 months led to increasing plasma levels at 12 months that were 3 × (HMTM) and 5 × (MTC) above linear model predictions.

CONCLUSIONS: The exposure increase at 12 months and the dual pharmacology of HMT explain the unexpected symptomatic activity of low dose MTC. The data suggest it is not possible to maintain comparable urinary discolouration without therapeutic activity in a standard placebo-controlled trial design.},
}

@article {pmid41917788,
year = {2026},
author = {Lu, M and Zhang, Y and Li, CS and Shan, G},
title = {Penalized estimation of linear transformation models for interval-censored data with time-dependent covariates.},
journal = {Statistical methods in medical research},
volume = {},
number = {},
pages = {9622802261433000},
doi = {10.1177/09622802261433000},
pmid = {41917788},
issn = {1477-0334},
abstract = {We investigate efficient estimation strategies for partially linear transformation models with time-dependent covariates under interval censoring. The unknown monotone function is approximated using a monotone B-spline basis to enable flexible semiparametric modeling, and we develop a computationally efficient nested hybrid EM algorithm that integrates Newton's method with isotonic regression. To support large-sample inference, we propose a straightforward variance-covariance estimation procedure for the regression parameters and introduce a score test to assess the adequacy of the proportional hazards (PH) specification within the broader class of transformation models. The numerical performance of the penalized estimators is examined extensively and compared with both the time-invariant covariate model by Lu et al. and the semiparametric transformation model by Zeng et al. Finally, the proposed methodology is applied to data from the National Alzheimer's Coordinating Center (NACC) to demonstrate its practical utility in a real-world clinical setting.},
}

@article {pmid41918005,
year = {2026},
author = {Singh, S and Sharma, Y and Bhardwaj, P and Kothari, D and Chhikara, A and Gupta, V and Kumar, D and Choudhary, N and Kondaveeti, SB},
title = {Next generation preventive neurology: how artificial intelligence and machine learning are reshaping Alzheimer's disease research.},
journal = {Behavioral and brain functions : BBF},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12993-026-00329-x},
pmid = {41918005},
issn = {1744-9081},
}

@article {pmid41918026,
year = {2026},
author = {Fang, M and Yan, Y and Song, W and Geng, Z and Wang, L and Hu, C and Li, W and Song, B and Chen, M and Dai, Y and Hu, Y and Zhou, S and Guo, H and Ji, G and Hu, P and Wang, K and Wu, X},
title = {Effects of 40-Hz transcranial alternating current stimulation on cognition and neural markers in Alzheimer's disease: a randomized, sham-controlled trial.},
journal = {Alzheimer's research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13195-026-02033-4},
pmid = {41918026},
issn = {1758-9193},
support = {No.2022ZD0214100//Ministry of Science and Technology of the People's Republic of China/ ; 82171917 and 82471271//Innovative Research Group Project of the National Natural Science Foundation of China/ ; 82090034 and 31970979//Innovative Research Group Project of the National Natural Science Foundation of China/ ; 82101498//Innovative Research Group Project of the National Natural Science Foundation of China/ ; },
}

@article {pmid41918193,
year = {2026},
author = {Behrouzfar, H and Mortazavi, P and Hassani, S and Aghebat Bekheir, S},
title = {Exploring the Effects of Empagliflozin Administration and Physical Training on Cognitive Functions in an Amyloid Beta-Induced Alzheimer's Rat Model.},
journal = {Current medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.2174/0109298673434008260121111535},
pmid = {41918193},
issn = {1875-533X},
abstract = {INTRODUCTION: Alzheimer's disease (AD) is a widely prevalent and neurodegenerative disorder that leads to dementia and mortality worldwide. Previous investigations have reported the beneficial effects of physical exercise on brain function, linked to anti-inflammatory effects in the brain vasculature and elevated BDNF production. Empagliflozin, a conventional antidiabetic agent, has shown potential neuroprotective properties in the central nervous system, evidenced by its ability to elevate BDNF and mitigate oxidative stress and inflammation.

MATERIALS AND METHODS: In the present investigation, AD was induced in control, exercise, empagliflozin (10 mg/kg BW, PO), and combined intervention groups using intrahippocampal injections of an amyloid-beta (Aβ) prepared solution via stereotaxic surgery. The therapeutic effects of each treatment, exercise alone, empagliflozin alone, and exercise plus empagliflozin, were studied. After 28 days, spatial memory tests were used to assess memory and learning. Furthermore, histopathological (H&E and Congo red) and immunohistochemical (GFAP) analyses were performed, and the ADP/ATP ratio in isolated brain mitochondria was measured by HPLC.

RESULTS: Our results showed that the combined program of physical training and empagliflozin treatment in the Aβ-induced AD model drastically improved cognitive functions and neurological parameters, including target-finding time, traveled distance, time spent in the target quadrant, and ADP/ATP ratios in brain mitochondria. Additionally, it diminished necrotic cell death and reduced Aβ plaques but did not notably affect astrocyte activity.

DISCUSSION: Exercise and empagliflozin, by affecting mitochondrial energy balance and reducing amyloid deposition, play key roles in mitigating AD pathophysiology.

CONCLUSION: The combined effects of the treatments used in this experimental method yielded significant improvements in cognitive functions. These findings provide a basis for further clinical studies for the exploration of the synergistic impact of the aforementioned therapeutic methods.},
}

@article {pmid41918200,
year = {2026},
author = {Khanal, P and Balmik, A},
title = {Neuroinflammation, Autophagy, and Neurodegeneration: Mechanisms and Therapeutic Insights.},
journal = {CNS & neurological disorders drug targets},
volume = {},
number = {},
pages = {},
doi = {10.2174/0118715273440234260304000039},
pmid = {41918200},
issn = {1996-3181},
abstract = {Neuroinflammation and autophagy dysregulation are critical in the pathogenesis of neurodegenerative diseases like Alzheimer's, Parkinson's, and Huntington's disease. Neuroinflammation occurs after a sustained immune response, which transitions into a chronic pathological state, leading to the sustained generation of pro-inflammatory cytokines and oxidative stress, causing neuronal damage. Meanwhile, defective autophagy exacerbates disease by promoting protein accumulation, e.g., amyloid-β, tau, and α-synuclein, thereby enhancing neuroinflammation. In this review, we focus on critical pathways, including mTOR and AMPK, that regulate these events and illustrate how their dysregulation may lead to a vicious cycle of inflammation and autophagy dysfunction. Novel therapeutic strategies, including mTOR inhibitors, autophagy enhancers, and inflammasome modulators, may contribute to cellular homeostasis. Furthermore, approaches that promote upregulation of chaperone- mediated autophagy can enable selective clearance of mediators of inflammatory response and aggregated/misfolded proteins. Advanced approaches such as CRISPR-based gene editing and RNA therapeutics provide tools to target molecular mechanisms involved in these neurodegenerative disorders, whereas the development of reliable biomarkers and novel delivery strategies may pave the way for personalized treatments. Moreover, artificial intelligence-based workflows and models may strengthen phenotypic and mechanistic screening of autophagy modulators and potential drug targets. By incorporating these forthcoming insights, this review underscores the critical need for comprehensive therapies that target both neuroinflammation and autophagy dysfunction to mitigate disease progression and improve patient outcomes.},
}

@article {pmid41918201,
year = {2026},
author = {Sharma, S and Sharma, D and Sharma, A},
title = {Targeting Vascular Dementia: Pharmacological Mechanisms and Therapeutic Strategies.},
journal = {CNS & neurological disorders drug targets},
volume = {},
number = {},
pages = {},
doi = {10.2174/0118715273440657260226125023},
pmid = {41918201},
issn = {1996-3181},
abstract = {INTRODUCTION: Vascular dementia is a leading cause of cognitive deterioration worldwide, caused by a complex interplay of pathological mechanisms such as disrupted cerebral blood flow, oxidative stress, neuroinflammation, and endothelial dysfunction. A clear knowledge of these mechanisms is crucial for developing efficient treatment strategies. Various drug classes, including statins, cholinesterase inhibitors, anti-diabetic drugs, leukotriene antagonists, and nootropics, offer promising approaches by addressing different facets of this multifaceted condition. This review's objective is to offer a comprehensive analysis of the functional mechanisms of diverse pharmacological agents in curing vascular dementia. It further aims to identify their therapeutic potential, limitations, and areas requiring future research.

METHODOLOGY: A review of the literature was conducted to examine evidence from preclinical and clinical research. Pharmacological chemicals were evaluated for their effects on key pathological pathways, including oxidative stress, inflammation, endothelial dysfunction, and impaired neurotransmission.

RESULT AND DISCUSSION: Each class of drugs reviewed demonstrates distinct benefits in addressing specific aspects of vascular dementia. Statins primarily mitigate vascular risk factors and neuroinflammation, while cholinesterase inhibitors enhance neurotransmitter availability to support cognitive function. Anti-diabetic drugs exhibit neuroprotective properties through metabolic regulation and antiinflammatory effects, and leukotriene antagonists show potential in reducing oxidative damage and inflammation. Nootropics, on the other hand, focus on enhancing synaptic plasticity and memory. Despite these promising mechanisms, limitations such as inconsistent clinical outcomes, potential adverse effects, and the absence of individualized treatment protocols remain significant challenges.

CONCLUSION: This review emphasizes the need for developing integrated therapeutic strategies that target the diverse pathological mechanisms underlying vascular dementia. While current pharmacological approaches show considerable potential, there is a desperate need for long-term clinical validation and the development of personalized medicine frameworks. Advances in diagnostic tools, biomarkers, and imaging technologies will be crucial for early diagnosis and effective disease monitoring, paving the way for improved patient results and a more profound understanding of vascular dementia's complexity.},
}

@article {pmid41918206,
year = {2026},
author = {Bazzari, FH and Bazzari, AH},
title = {Amyloid-Beta Immunotherapies for Alzheimer's Disease: Current Progress.},
journal = {Current Alzheimer research},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115672050468315260226041235},
pmid = {41918206},
issn = {1875-5828},
abstract = {Alzheimer's Disease (AD) is a major global challenge and the most common cause of dementia worldwide. Accumulation of Amyloid-Beta (Aβ) is considered a key factor in AD pathophysiology and progression, and is linked to disruptions of neuronal integrity and the initiation of several downstream neurodegenerative cascades. Immunotherapeutic agents targeting Aβ have emerged as potential disease-modifying drug candidates, and extensive efforts have been dedicated to both active and passive modalities. Early Aβ vaccines demonstrated proof of concept; however, they were later discontinued due to several safety concerns, which, in turn, guided the refinement of epitope design and immune response modulation in the second-generation ones. On the other hand, early monoclonal antibodies have also faced challenges, such as variable efficacy and adverse events, particularly Amyloid-Related Imaging Abnormalities (ARIA), which ultimately led to their discontinuation. Nonetheless, recent regulatory advances have led to the approvals of Aduhelm® (Aducanumab), Leqembi® (Lecanemab), and Kisunla® (Donanemab), each of which has demonstrated the ability to reduce Aβ burden and slow cognitive decline. Despite these advancements, challenges persist regarding patient selection, biomarker-guided monitoring, ARIA risk reduction, long-term outcomes, and global accessibility. Notably, the clinical benefits observed to date remain modest, and it remains uncertain whether the currently approved Aβ-targeted immunotherapies achieve meaningful long-term disease modification. Collectively, the evolution of Aβ-targeted immunotherapies has provided further insights into the complexity of AD pathology and the challenges associated with future progress toward achieving effective disease modification. This paper aims to provide a comprehensive review of all Aβ-directed immunotherapies, both active and passive agents, that have advanced into clinical trials, including those currently approved, discontinued, or undergoing late-stage evaluation.},
}

@article {pmid41918207,
year = {2026},
author = {Mishra, R and Gupta, JK},
title = {Decoding microRNA-Protein Interaction Networks in Alzheimer's Disease: Molecular Mechanisms and Clinical Implications.},
journal = {Current Alzheimer research},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115672050451919260313061818},
pmid = {41918207},
issn = {1875-5828},
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by memory loss, cognitive decline, and neuronal dysfunction. Despite thorough research efforts, effective disease-modifying treatments have yet to be discovered. MicroRNAs (miRNAs), small noncoding RNAs that control gene expression after transcription, have become key factors in AD development. Changes in miRNA levels influence critical molecular pathways such as amyloid precursor protein (APP) processing, tau phosphorylation, oxidative stress, neuroinflammation, and synaptic plasticity, all of which contribute to neuronal damage. By increasing β-secretase (BACE1) activity, downregulation of miR-29a/b and miR-107 encourages the buildup of amyloid-β (Aβ) and the development of plaques. Through the deregulation of the CDK5 and MAPK pathways, overexpression of miR-125b and decreased levels of miR-132/212 lead to tau hyperphosphorylation. While oxidative stress-associated miRNAs like miR-34a and miR- 21 worsen mitochondrial malfunction and neuronal death, pro-inflammatory miRNAs like miR-146a and miR-155 cause NF-κB-mediated signalling and glial activation. Circulating miRNAs found in blood and cerebral fluid are potential, minimally invasive indicators for tracking the course of a disease and making early diagnoses. Additionally, therapeutic manipulation with antagomiRs or miRNA mimics has the potential to prevent neurodegeneration and restore normal gene regulation. This review deciphers the molecular mechanisms underlying miRNA dysregulation in AD and explores their translational potential as biomarkers and therapeutic targets. A comprehensive understanding of miRNA-protein interaction networks could facilitate the development of targeted, precision- based interventions for Alzheimer's disease.},
}

@article {pmid41918278,
year = {2026},
author = {Li, D and Zheng, K and Zhang, R and Zhuo, L and Nie, W and Jia, M and Wei, X and Cui, H},
title = {Chemiluminescent Nanoflower with Inherent Oxygen Vacancies for Coreactant-Free and Label-Free Immunoassay of pTau181.},
journal = {Analytical chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.analchem.5c06993},
pmid = {41918278},
issn = {1520-6882},
abstract = {The detection of phosphorylated tau (pTau181), a key biomarker for Alzheimer's disease, remains challenging due to its ultralow physiological concentration. Chemiluminescent sandwich immunoassays provide high sensitivity, but their accuracy is compromised by truncated tau fragments that lack the secondary antibody epitope as well as by the instability of peroxide-based coreactants. Here, we developed a nanoflower with inherent oxygen vacancies, synthesized through a one-pot method, involving 8-amino-5-chloro-2,3-dihydro-7-phenylpyrido[3,4-d]pyridazine-1,4-dione (L012), dicarboxylic ferrocene (Fc), and HAuCl4, named L012-Au-Fc nanoflower (LAF-NF). As a self-sufficient chemiluminescent microreactor, LAF-NF can efficiently catalyze adsorbed dissolved oxygen to generate strong, stable chemiluminescent emission without peroxide coreactants, achieving a 161-fold enhancement in the intensity over the L012 system. On this basis, a coreactant-free and label-free immunoassay for pTau181 using LAF-NF as the nanointerface was designed. The LAF-NF sensor achieved an ultrasensitive detection limit of 2.9 fg/mL and demonstrated excellent selectivity over total tau, theoretically eliminating immunoassay errors caused by epitope loss. This work offers a powerful platform for early Alzheimer's disease diagnostics.},
}

@article {pmid41918343,
year = {2026},
author = {Lopes, SP and Emídio, JJ and Duarte, ABS and Orhan, IE and Deniz, FSS and Salmas, RE and de Sousa, DP},
title = {Synthesis of p-Coumarates With Potential Anti-Alzheimer's Action: Enzyme Inhibition and In Silico Studies.},
journal = {Chemistry & biodiversity},
volume = {23},
number = {4},
pages = {e03857},
doi = {10.1002/cbdv.202503857},
pmid = {41918343},
issn = {1612-1880},
support = {306661/2016-0//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; //Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; },
mesh = {*Cholinesterase Inhibitors/chemical synthesis/chemistry/pharmacology ; *Butyrylcholinesterase/metabolism ; *Alzheimer Disease/drug therapy/metabolism ; *Acetylcholinesterase/metabolism ; Humans ; *Coumaric Acids/chemistry/chemical synthesis/pharmacology ; Structure-Activity Relationship ; Molecular Docking Simulation ; Molecular Structure ; Dose-Response Relationship, Drug ; Propionates/chemistry/chemical synthesis/pharmacology ; },
abstract = {Alzheimer's disease (AD) is a fatal neurodegenerative disorder that affects cognition, memory, and behavior. Such a disease is considered the most common cause of dementia and affects a large portion of the elderly population worldwide. Currently, cholinesterase inhibitors are used to reduce the symptoms and rate of progression of this disease. Thus, the present study evaluated the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities of a set of 22 p-coumarate derivatives using the spectrophotometric method. The inhibitory activity of the compounds against AChE and BChE was measured using the adapted Ellman spectrophotometric method; the reported inhibition percentages were determined at a final concentration of 100 µM. The structures of the synthesized compounds were characterized by FTIR, [1]H-NMR, [13]C-NMR, and HRMS spectroscopy. Among the compounds tested, three showed moderate inhibitory activity against AChE and good activity against BChE: (E)-4-chlorobenzyl 3-(4-hydroxyphenyl)acrylate (14) (56.36%; 75.17%), (E)-4-bromobenzyl 3-(4-hydroxyphenyl)acrylate (15) (61.11%; 76.09%), and (E)-naphthalene 3-(4-hydroxyphenyl)acrylate (18) (59.18%; 65.39%), respectively. Compound 15 had an IC50 of 22.22 ±1.50 mM against BChE, which is notably better than galantamine's BChE inhibition. The in silico analysis suggested that compounds 14, 15, and 18 interact with AChE and BChE. Thus, p-coumaric acid derivatives represent promising prototypes for the search for new drug candidates for the treatment of AD.},
}

*Cholinesterase Inhibitors/chemical synthesis/chemistry/pharmacology
*Butyrylcholinesterase/metabolism
*Alzheimer Disease/drug therapy/metabolism
*Acetylcholinesterase/metabolism
Humans
*Coumaric Acids/chemistry/chemical synthesis/pharmacology
Structure-Activity Relationship
Molecular Docking Simulation
Molecular Structure
Dose-Response Relationship, Drug
Propionates/chemistry/chemical synthesis/pharmacology

@article {pmid41918394,
year = {2026},
author = {Verma, P and Dhamdhere, T and Shaikh, A and Saxena, H and Saha, S and Bapat, S},
title = {AI-Driven Multimodal Analysis of Neuroimaging and Speech Data for Diagnosis of Alzheimer's, Parkinson's, and Epilepsy.},
journal = {Biotechnology and applied biochemistry},
volume = {},
number = {},
pages = {},
doi = {10.1002/bab.70169},
pmid = {41918394},
issn = {1470-8744},
abstract = {This study investigates the application of machine learning (ML) techniques combined with neuroimaging and speech signal processing for the early detection of neurological disorders, including Alzheimer's disease, Parkinson's disease, and epilepsy. A multisource analysis dataset consisting of neuro-images and speech features was utilized to train and evaluate various ML classifiers, such as K-nearest neighbors (KNN), Support Vector Machines, Random Forest, Naive Bayes, Decision Trees, XGBoost, and ADABoost. Performance assessment was based on metrics like accuracy, precision, recall, F1 score, and AUC-ROC. Among all models, KNN demonstrated the highest diagnostic accuracy and overall performance, with an accuracy of 92.8% and an F1 score of 0.953. The results suggest that KNN is particularly well-suited for classifying neurological conditions using integrated biomedical data. Although these findings highlight the promise of artificial intelligence (AI)-driven approaches in neurological diagnostics, further validation with diverse datasets is recommended to improve generalizability and clinical relevance.},
}

@article {pmid41918502,
year = {2026},
author = {Chesters, J},
title = {Tau Pathology in Chronic Traumatic Encephalopathy: Mechanisms and Diagnostic Advances.},
journal = {The Yale journal of biology and medicine},
volume = {99},
number = {1},
pages = {193-198},
pmid = {41918502},
issn = {1551-4056},
mesh = {Humans ; *Chronic Traumatic Encephalopathy/diagnosis/metabolism/pathology ; *tau Proteins/metabolism ; *Tauopathies/metabolism/diagnosis/pathology ; Brain/pathology/metabolism ; },
abstract = {Chronic Traumatic Encephalopathy (CTE) is a progressive neurodegenerative tauopathy associated with repetitive head impacts (RHI), yet it remains diagnosable only at post-mortem. Tau, a microtubule-associated protein, normally stabilizes neuronal microtubules and regulates cytoskeletal dynamics. Mechanical strain from RHI is thought to disrupt calcium homeostasis and kinase-phosphatase balance, driving hyperphosphorylation and phosphorylated-tau (p-tau) formation. This results in detachment from microtubules and subsequent p-tau aggregation. These mechanically-induced biochemical changes produce CTE's characteristic lesion: perivascular p-tau deposition in the depths of cortical sulci, reflecting the non-uniform mechanical loading experienced by brain tissue following head impacts. Advances in molecular neuropathology have revealed that CTE tau filaments adopt a unique conformational fold, and that early tau species may contribute to neurotoxicity. Despite this growing understanding, antemortem diagnosis remains challenging. Structural MRI demonstrates frontotemporal atrophy and white-matter abnormalities in impact-exposed individuals, but these findings lack disease specificity. Tau-PET tracers developed for Alzheimer's disease (AD) show limited affinity for the distinct CTE tau fold, while fluid biomarkers variably reflect cumulative exposure but cannot yet discriminate CTE from other tauopathies. Future progress will depend on mechanistically informed diagnostic tools, including conformation-specific biomarkers and PET radiotracers tailored to CTE-specific tau. Multimodal approaches integrating neuroimaging, molecular profiling, exposure metrics, and computational modelling will be essential for early detection, disease monitoring, and informed public health policy around repetitive head impacts.},
}

Humans
*Chronic Traumatic Encephalopathy/diagnosis/metabolism/pathology
*tau Proteins/metabolism
*Tauopathies/metabolism/diagnosis/pathology
Brain/pathology/metabolism

@article {pmid41918503,
year = {2026},
author = {Galbraith, JA and Elhassan, MZ and Rocha, JF and Al Mozani, TA and Fredericks, CA},
title = {Gonadotropins Across the Lifespan: Their role in the Neurodevelopment-Neurodegeneration Continuum.},
journal = {The Yale journal of biology and medicine},
volume = {99},
number = {1},
pages = {199-215},
pmid = {41918503},
issn = {1551-4056},
mesh = {Humans ; *Gonadotropins/metabolism ; Female ; Brain/metabolism ; *Longevity/physiology ; Animals ; *Neurodegenerative Diseases/metabolism ; },
abstract = {Gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), mediate critical reproductive functions via the hypothalamus-pituitary-gonadal axis. Their levels fluctuate across the lifespan, particularly during puberty and menopause, and across the menstrual cycle. In addition to peripheral expression, gonadotropin receptors are widely expressed in the brain, notably in memory-associated regions such as the hippocampus and cortex. Alterations in FSH and LH during reproductive transitions correlate with structural and functional brain changes. Puberty disorders, including central precocious puberty (CPP) and congenital hypogonadotropic hypogonadism (CHH), show altered gray and white matter and functional connectivity in the default mode network (DMN), which supports memory and is disrupted early in Alzheimer's disease (AD). Although preclinical evidence implicates gonadotropins in amyloid and tau pathology, studies of attention and memory have yielded inconsistent results. However, reproductive disorders such as primary ovarian insufficiency (POI) and polycystic ovary syndrome (PCOS) are associated with deficits in cognitive performance, altered DMN dynamics, and increased AD risk. Menopause, characterized by marked gonadotropin elevation, is also accompanied by alterations in brain structure, connectivity, amyloid and tau deposition, and cognition, with associations with FSH and LH that are underexplored. This review synthesizes a broad range of basic and clinical evidence across reproductive transitions and disorders, highlighting shared and distinct mechanisms by which gonadotropins influence brain development, aging, and AD risk, and suggesting directions for future research.},
}

Humans
*Gonadotropins/metabolism
Female
Brain/metabolism
*Longevity/physiology
Animals
*Neurodegenerative Diseases/metabolism

@article {pmid41918511,
year = {2026},
author = {Moret, S and Galbraith, JA and Lorenzon, G and Mehr, SA and Fredericks, CA},
title = {Musicality is Preserved in Neurodegeneration.},
journal = {The Yale journal of biology and medicine},
volume = {99},
number = {1},
pages = {243-256},
pmid = {41918511},
issn = {1551-4056},
mesh = {Humans ; *Music ; *Neurodegenerative Diseases/physiopathology ; *Alzheimer Disease/physiopathology ; Brain/physiopathology ; *Frontotemporal Dementia/physiopathology ; Auditory Perception/physiology ; Emotions/physiology ; },
abstract = {Certain musical abilities can endure even as language, memory, and behavior decline in dementia, yet the neural basis of this resilience remains poorly understood. We draw on behavioral and neuroimaging evidence to explain why musicality is selectively preserved or impacted across Alzheimer's disease (AD) and the frontotemporal dementias (FTDs). Adopting a network-based perspective, we describe how musicality arises from interactions across large-scale brain systems that support perception, emotion, and memory. Evidence from case studies and neuroimaging work suggests that music engages lower-level auditory processing and higher-order networks across the brain, which may help explain the heterogeneous effects of neurodegeneration on musicality. Preserved and impaired musical abilities may reflect the selective vulnerability of distinct intrinsic connectivity networks. In early AD, relatively preserved salience and reward circuitry may sustain emotional responses to familiar music and facilitate autobiographical recall even as episodic memory declines. Degeneration of anterior temporal and salience network regions in the FTDs may disrupt the emotional and conceptual interpretation of music while leaving lower-level auditory systems relatively intact. Significant gaps remain in understanding how different components of musicality are affected in specific neurodegenerative diseases. Greater methodological standardization, larger cohorts, longitudinal study designs, and multimodal approaches will be critical for identifying how musicality is preserved or impacted across dementia syndromes. Addressing these questions may advance theoretical models of music perception in the human brain and guide the development of targeted music-based interventions that enhance emotion, memory, and quality of life for people living with dementia.},
}

Humans
*Music
*Neurodegenerative Diseases/physiopathology
*Alzheimer Disease/physiopathology
Brain/physiopathology
*Frontotemporal Dementia/physiopathology
Auditory Perception/physiology
Emotions/physiology

@article {pmid41918768,
year = {2026},
author = {Li, X and Olofsson, J and Persson, J},
title = {Structural connectivity of the human olfactory network and its relation to aging and olfactory function.},
journal = {Imaging neuroscience (Cambridge, Mass.)},
volume = {4},
number = {},
pages = {},
pmid = {41918768},
issn = {2837-6056},
abstract = {Impaired olfactory function in older adults is associated with memory decline and is a biomarker of Alzheimer's disease (AD). However, the structural brain foundation underlying olfactory impairment and its link to memory function remains largely unknown. We address this gap by reconstructing the structural olfactory network, that is, white-matter connections between the primary olfactory cortex (POC) and the whole brain. Through applying multivariate analyses in a population-based sample (n = 137), we investigate the relationships among age, the olfactory network, and olfactory and cognitive function. Our findings reveal that the POC subregions have distinct structural connectivity profiles with the entire brain. Older age was associated with weaker connectivity strength between the POC and nearby regions, suggesting a reorganization of the olfactory network in older adults. Structural connectivity of the olfactory network was associated with behavioral performance in odor identification, episodic memory, and odor threshold, but not processing speed or working memory. Notably, connections including the olfactory tubercle (TUB)-caudate, TUB-amygdala, and olfactory nucleus (AON)-hippocampus were important for both olfaction and episodic memory function, suggesting a common neural basis across cognitive domains. Our study expands on previous research of single brain regions or individual white-matter tracts, uncovering the structural underpinnings of olfactory function at the network level. The results shed light on the common foundation of olfaction and memory dysfunction, an early marker of AD.},
}

@article {pmid41918990,
year = {2026},
author = {Roe, KV and Grassi, S and Chiola, S and Miller, RJ},
title = {Editorial: Advances in neurodevelopmental and neurodegenerative disease research: focus on innovative human-relevant brain research.},
journal = {Frontiers in neuroscience},
volume = {20},
number = {},
pages = {1818513},
doi = {10.3389/fnins.2026.1818513},
pmid = {41918990},
issn = {1662-4548},
}

@article {pmid41919006,
year = {2026},
author = {Buchanan, TJ and Ewen, C and Rebollo Mesa, I and Germani, M and Watanabe, S and Jose, J and Famodimu, O and Colson, AO and De Bruyn, S},
title = {Two phase 1 randomised studies investigating the safety and pharmacokinetics of bepranemab in healthy participants of different ethnicities.},
journal = {BMJ neurology open},
volume = {8},
number = {1},
pages = {e001395},
pmid = {41919006},
issn = {2632-6140},
abstract = {BACKGROUND: Bepranemab is a recombinant, humanised, full-length IgG4 monoclonal antibody targeting a mid-region tau epitope. Two phase 1 studies assessed the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of bepranemab.

METHODS: UP0047 (NCT03464227) and UP0065 (NCT03605082) were phase 1, double-blind, placebo-controlled, single-dose, dose-escalation studies of intravenous bepranemab in healthy participants (Caucasian and Japanese descent, respectively). Primary endpoint: safety and tolerability of single ascending doses of bepranemab. PK were assessed in serum and cerebrospinal fluid (CSF); PD (levels of free tau) in CSF. A physiologically based PK/PD (PBPK/PD) model was developed to predict dose response.

RESULTS: UP0047: Caucasian participants (N=52) were randomised to bepranemab 0.3 mg/kg, n=2; 1 mg/kg, n=6; 3 mg/kg, n=6; 10 mg/kg, n=6; 30 mg/kg, n=6; 60 mg/kg, n=6; 120 mg/kg, n=6; placebo, n=14). UP0065: participants of Japanese descent (N=24) were randomised to bepranemab 30 mg/kg, n=6; 60 mg/kg, n=6; 120 mg/kg, n=6; placebo, n=6). No serious treatment-emergent adverse events (TEAEs) or discontinuations due to TEAEs were observed. One participant (bepranemab 60 mg/kg) experienced treatment-related TEAEs of headache (moderate intensity), nausea and vomiting (mild intensity). There was no effect of ethnicity on PK parameters. A dose-response effect of bepranemab on free tau levels was observed. Data applied to a PBPK/PD model supported a dose of 90 mg/kg of bepranemab every 4 weeks to achieve a reduction in mean change from baseline in free tau levels of up to 90%.

CONCLUSIONS: Safety, PK and PD data support continued investigation of bepranemab for the treatment of tauopathies.},
}

@article {pmid41919213,
year = {2026},
author = {Ahmad, A and Salar, U and Özil, M and Baltaş, N and Nasim, M and Ullah, A and Ul-Haq, Z and Khan, KM and Shaheen, F},
title = {Multitarget synthetic piperates against key drug targets of Alzheimer's and diabetes mellitus.},
journal = {RSC advances},
volume = {16},
number = {19},
pages = {17085-17113},
pmid = {41919213},
issn = {2046-2069},
abstract = {A library of piperate derivatives 3-25 was synthesized in a two-step reaction scheme starting from piperine 1, which was converted to piperic acid 2 first, and then reacted with various alkyl and aryl halides to afford the final products. Compounds were fully characterized and evaluated for their multitarget potential against well-established drug targets involved in diabetes and Alzheimer's diseases. In vitro assay revealed strong inhibitory activity against acetylcholinesterase (AChE), butylcholinesterase (BChE), α-glucosidase, and α-amylase. Compounds 6-15, 19, and 21-23 were potent inhibitors of AChE, and compounds 6-8, 12-15, 19, and 21-23 were also more effective inhibitors of BChE than the standard donepezil. Compounds bearing halogens (F, Cl, and Br) exhibited noteworthy inhibitory potency against both targets. In addition, compounds 2, 3, 17, 18, and 25 were recognized as potent α-glucosidase and α-amylase inhibitors, outperforming standard acarbose. In particular, piperic acid (2) and compounds containing the cyanomethyl (compound 3), 3-methoxyphenyl (compounds 17, 18), and 2-nitrophenyl (compound 25) moieties showed remarkable inhibitory potential. Further, kinetic studies were conducted to unravel the inhibition mechanism against all four enzymes, while in silico studies identified key interactions between inhibitors and the active-site residues of each target. All compounds also displayed reasonable antioxidant potential, as evidenced by FRAP, CUPRAC, and DPPH assays, compared with the standard butylated hydroxytoluene (BHT). Detailed pharmacokinetic and ADME profiles were also predicted to assess the druggability of the compounds. The identified ligands have multitarget potential to inhibit the key enzymes associated with diabetes and Alzheimer's. They may serve as lead candidates for later stages of drug development.},
}

@article {pmid41919222,
year = {2026},
author = {Spatafora, MG and Dubin, J and Domi, T and Lombardi, R and Cabras, P and Dalla Bella, E and Consonni, M and Quattrini, A and Verri, M and Lauria, G and Van Damme, P and Poesen, K and Riva, N and Peviani, M},
title = {Increased CSF levels of soluble AXL at diagnosis correlate with poor prognosis in patients affected by amyotrophic lateral sclerosis.},
journal = {Brain communications},
volume = {8},
number = {2},
pages = {fcag086},
pmid = {41919222},
issn = {2632-1297},
abstract = {AXL, a receptor tyrosine kinase expressed in neurons and glial cells, involved in neuronal survival, myelination, and regulation of immune responses, can undergo shedding due to the activation of metalloproteases in neuroinflammatory conditions. Indeed, CSF and serum levels of soluble AXL (sAXL) have been correlated with neurodegeneration and cognitive decline in Alzheimer's disease (AD). Based on these observations, we explored whether sAXL is implicated in amyotrophic lateral sclerosis (ALS). sAXL levels were measured in biofluids (CSF and serum) from two biorepositories, totalling 107 ALS patients, 76 healthy controls, 25 AD patients, 22 patients with multiple sclerosis and 51 patients with ALS disease mimicking disorders (i.e. patients that displayed symptoms resembling ALS, in whom eventually ALS was excluded after a thorough clinical examination). Gender and age were considered as covariate in the statistical analyses. Our results provide the first evidence of sAXL alterations in the CSF and serum of ALS patients at diagnosis and demonstrate a significant association between CSF sAXL levels and disease progression, as well as its prognostic value in ALS. While these observations require validation through multicentre studies, they suggest the involvement of the AXL pathway in ALS pathology and pave the way for leveraging CSF sAXL levels as a biomarker to aid ALS disease stratification.},
}

@article {pmid41919360,
year = {2026},
author = {Kloppenburg-Lagendijk, M and Huitema, Y and van Harten, A and Hempenius, L and Verwey, N},
title = {[The Clinical Applicability of Blood Biomarkers for Alzheimer's disease in the Memory Clinic].},
journal = {Tijdschrift voor gerontologie en geriatrie},
volume = {57},
number = {1},
pages = {10-27},
doi = {10.54195/tgg24597},
pmid = {41919360},
issn = {0167-9228},
mesh = {Humans ; *Alzheimer Disease/diagnosis/blood ; *Biomarkers/blood ; tau Proteins/blood ; Aged ; Amyloid beta-Peptides/blood ; Glial Fibrillary Acidic Protein/blood ; Neurofilament Proteins/blood ; },
abstract = {BACKGROUND: The development of highly sensitive assays has enabled the detection of biomarkers of Alzheimer's disease in blood. In this literature review, we discuss their clinical applicability based on recent studies.

METHODS: A systematic search was conducted across Embase, Pubmed, Web of Science, Cochrane Central, and Google Scholar for studies published since 2021, using the search terms 'Alzheimer's Disease', 'Blood Biomarkers' and 'Memory Clinic'.

RESULTS: Based on the 11 included studies, pTau181, pTau217, NfL and GFAP appear to be clinically relevant (diagnostic value, AUC > 0.7) as blood biomarker.

CONCLUSIONS: Multiple blood biomarkers appear to be clinically relevant for diagnostics in a memory clinic setting. However, this conclusion is based on just 11 studies, highlighting the need for further research in real-world populations within memory clinics.},
}

Humans
*Alzheimer Disease/diagnosis/blood
*Biomarkers/blood
tau Proteins/blood
Aged
Amyloid beta-Peptides/blood
Glial Fibrillary Acidic Protein/blood
Neurofilament Proteins/blood

@article {pmid41919455,
year = {2026},
author = {Fujioka, S and Nagaishi, Y and Imamura, T and Minagawa, H and Uwatoko, K and Yukitake, M and Kira, JI and Tsuboi, Y},
title = {Amyloid PET-guided anti-amyloid therapy in corticobasal syndrome associated with clinical improvement.},
journal = {Neurologia i neurochirurgia polska},
volume = {},
number = {},
pages = {},
doi = {10.5603/pjnns.110307},
pmid = {41919455},
issn = {0028-3843},
abstract = {AIM OF THE STUDY: Corticobasal syndrome (CBS), a heterogeneous clinical phenotype, can be associated with various underlying pathologies. Although neuropathological studies show that CBS cases can be attributed to Alzheimer's disease (AD), in vivo confirmation and subsequent disease-modifying therapy remain rarely reported. In our patients presenting with clinical features consistent with CBS, amyloid positron emission tomography (PET) facilitated the diagnosis of underlying AD pathology and enabled the initiation of anti-amyloid therapy.

MATERIAL AND METHODS: We retrospectively reviewed patients with probable corticobasal degeneration from two tertiary centers who underwent amyloid PET confirming AD, systematically collecting clinical, imaging, and treatment data.

RESULTS: Two patients were identified who fulfilled the inclusion criteria. In both patients, episodic memory was impaired, which was inconsistent with a typical corticobasal syndrome phenotype. Amyloid PET demonstrated widespread cortical and subcortical amyloid deposition, confirming underlying AD pathology. Based on these findings, anti-amyloid therapy was initiated, and clinical improvement was observed in both patients, although causality cannot be inferred from this uncontrolled retrospective observation.

CONCLUSIONS: Corticobasal syndrome may be an atypical clinical presentation of AD pathology. Importantly, molecular imaging allowed an in vivo diagnosis of AD and facilitated the timely initiation of anti-amyloid therapy.

CLINICAL IMPLICATIONS: This novel report documents the clinical implementation of amyloid PET guided anti-amyloid therapy in patients presenting with CBS.},
}

@article {pmid41919473,
year = {2026},
author = {Cheng, Y and Qiu, M and Yu, Z and Tang, X and Zhang, J},
title = {Long non-coding RNAs in neurodegenerative diseases - Molecular mechanisms, liquid biopsy biomarkers, and therapeutic targets: A review.},
journal = {Biomolecules & biomedicine},
volume = {},
number = {},
pages = {},
doi = {10.17305/bb.2026.13978},
pmid = {41919473},
issn = {2831-090X},
abstract = {Neurodegenerative diseases (NDDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD), are age-related disorders characterized by progressive neuronal loss, cognitive decline, and limited options for disease-modifying treatments. Increasing evidence suggests that long non-coding RNAs (lncRNAs) play significant roles in neurodevelopment, neuronal homeostasis, and disease progression; however, their involvement in shared pathogenic pathways and clinical applications remains inadequately defined. This review consolidates recent experimental, transcriptomic, bioinformatic, and emerging clinical findings regarding the role of lncRNAs in NDDs. We examine how lncRNAs modulate common disease mechanisms, including protein misfolding and aggregation, neuroinflammation, mitochondrial dysfunction, ferroptosis, synaptic failure, and aging-related neurodegenerative processes. These regulatory functions occur through various mechanisms, including epigenetic modifications, transcriptional regulation, post-transcriptional processes, and RNA-protein interactions, as well as novel mechanisms such as liquid-liquid phase separation (LLPS), peptide coding, and exosome-mediated intercellular communication. Current evidence supports the potential of lncRNAs as minimally invasive liquid biopsy biomarkers, detectable in blood, cerebrospinal fluid (CSF), and extracellular vesicles. Additionally, lncRNAs may serve as therapeutic targets through antisense oligonucleotides (ASOs), gene editing, and engineered delivery platforms. Overall, lncRNAs have emerged as central molecular regulators and promising candidates for translation in NDDs. Nonetheless, challenges related to specificity, validation, delivery across the blood-brain barrier, and clinical standardization must be addressed before their routine application in precision neurology.},
}

@article {pmid41919495,
year = {2026},
author = {De Tito, S and Tooze, SA},
title = {Lysosomal homeostasis at the crossroads of neurodegeneration.},
journal = {The Journal of clinical investigation},
volume = {136},
number = {7},
pages = {},
doi = {10.1172/JCI199845},
pmid = {41919495},
issn = {1558-8238},
mesh = {Humans ; *Lysosomes/metabolism/pathology/genetics ; *Neurodegenerative Diseases/metabolism/pathology/genetics ; Animals ; *Homeostasis ; Endosomal Sorting Complexes Required for Transport/metabolism/genetics ; *Neurons/metabolism/pathology ; },
abstract = {Lysosomes function as metabolic control centers that integrate degradation, nutrient sensing, and stress signaling. In neurons, which must maintain proteostasis and energetic balance throughout life, lysosomal homeostasis determines cellular resilience. Emerging evidence identifies lysosomal injury and defective repair as common denominators across neurodegenerative diseases. Damage to the lysosomal membrane caused by oxidative stress, lipid imbalance, or genetic mutations triggers a hierarchical quality control cascade. Early lesions recruit the endosomal sorting complex required for transport (ESCRT) machinery for mechanical resealing, while larger ruptures activate lipid-centered recovery modules. When repair fails, lysophagy eliminates irreparable organelles and a TFEB-dependent transcriptional program regenerates the lysosomal pool. These tightly coupled responses safeguard neurons from catastrophic proteostatic collapse. Their impairment, through mutations in lysosomal proteins, or through aging, produces the lysosomal fragility that underlies Alzheimer disease, Parkinson disease, amyotrophic lateral sclerosis/frontotemporal dementia, and Huntington disease. Crosstalk between lysosomes, mitochondria, and ER integrates local damage with systemic metabolic adaptation, while dysregulated lysosomal exocytosis and inflammation propagate pathology. Understanding how ESCRT complexes, lipid transport, and transcriptional renewal cooperate to preserve lysosomal integrity reveals unifying principles of neurodegeneration and defines molecular targets for intervention. Restoring lysosomal repair and renewal offers a rational path toward preventing neuronal loss.},
}

Humans
*Lysosomes/metabolism/pathology/genetics
*Neurodegenerative Diseases/metabolism/pathology/genetics
Animals
*Homeostasis
Endosomal Sorting Complexes Required for Transport/metabolism/genetics
*Neurons/metabolism/pathology

@article {pmid41919533,
year = {2026},
author = {King, JB and Prigge, MBD and Koppelmans, V and Hoffman, JM and Duff, K},
title = {Altered functional connectivity is associated with Repeatable Battery for the Assessment of Neuropsychological Status across the dementia spectrum.},
journal = {Journal of the International Neuropsychological Society : JINS},
volume = {},
number = {},
pages = {1-12},
doi = {10.1017/S135561772610191X},
pmid = {41919533},
issn = {1469-7661},
abstract = {OBJECTIVE: The quest for non-invasive and cost-effective biomarkers for mild cognitive impairment (MCI) and Alzheimer's disease (AD) has led to growing interest in resting-state functional magnetic resonance imaging (MRI). This study examined associations between whole-brain functional connectivity measures and cognitive performance across a spectrum of cognitive aging.

METHOD: A total of 108 older adults (mean age 74.1 ± 5.7 years), comprised of cognitively intact individuals, participants with amnestic MCI, and those with mild dementia due to probable AD, underwent high-resolution structural MRI and resting-state functional MRI scans and cognitive testing with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Functional connectivity values were derived from a 17-network brain parcellation. Correlations were established between network connectivity values and RBANS Index scores.

RESULTS: Analyses revealed that lower RBANS Attention Index and Total Scale scores were significantly associated with increased connectivity between the ventral attention, central executive network, and limbic and default mode networks. Lower RBANS total scores were also associated with functional connectivity strength between the dorsal default mode networks and lateral frontoparietal regions of the central executive network, with increased connectivity observed across the dementia spectrum (Intact-MCI-AD).

CONCLUSIONS: These findings suggest that aberrant and potentially compensatory increases in functional connectivity may be linked to cognitive decline, supporting the utility of resting-state functional MRI as a promising biomarker for MCI and AD.},
}

@article {pmid41919674,
year = {2026},
author = {Takai, A and Yoshida, K and Hiroshima, Y and Ikuta, A and Seyama, M and Uemura, Y and Yumoto, H and Ozaki, K},
title = {Porphyromonas gingivalis Outer Membrane Vesicles-Associated DNA Triggers Inflammation by Inducing IL-6 in Astrocytes.},
journal = {Molecular oral microbiology},
volume = {},
number = {},
pages = {},
doi = {10.1111/omi.70030},
pmid = {41919674},
issn = {2041-1014},
support = {//Center for Advanced Medical Sciences (Institute of Health Biosciences, University of Tokushima Graduate School)/ ; //Japan Society for the Promotion of Science/ ; },
abstract = {Porphyromonas gingivalis (Pg), a key pathogen in periodontal disease, is suggested to be involved in the progression of Alzheimer's disease (AD); however, the molecular mechanism remains unclear. We previously reported that Pg-released outer membrane vesicles (OMVs) were detected in the brains of mice after intraperitoneal administration. We here investigated the effects of Pg OMVs on astrocytes, the most abundant glial cells in the central nervous system, which are involved in neuroinflammation. We demonstrated that Pg OMVs increased the expression of interleukin-6 (IL-6) mRNA, which is associated with the pathogenesis of AD, in a Toll-like receptor (TLR)2/4-independent manner in human astrocyte SVG p12 cells. Whole-genome sequencing revealed that Pg OMVs contained Pg genomic DNA, which was critical for IL-6 mRNA induction. The tracking of fluorescent-labeled Pg OMV-associated DNA revealed that Pg OMVs were transported into SVG p12 cells. Endocytosis inhibitors attenuated IL-6 mRNA expression induced by Pg OMVs, suggesting that the incorporation of Pg OMVs by endocytosis is important for IL-6 mRNA induction. Furthermore, the incorporated Pg OMV-associated DNA increased IL-6 mRNA expression via the TLR9 pathway. Our study advances understanding of the role of Pg OMVs, which may contribute to the onset and progression of AD in periodontal disease.},
}

@article {pmid41919762,
year = {2026},
author = {Taylor, K and Howe, LD and Lacey, RE and Carslake, D and Anderson, E and Mukadam, N},
title = {The association between adverse experiences throughout the life-course and risk of dementia in the English Longitudinal Study of Ageing.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261431801},
doi = {10.1177/13872877261431801},
pmid = {41919762},
issn = {1875-8908},
abstract = {BackgroundPrevious studies investigating associations between adverse experiences across the life-course and dementia consider a narrow range of experiences and use sum scores which assume each experience has the same impact on dementia risk.ObjectiveTo develop a greater understanding of how patterns of adversity influence associations with dementia through consideration of timing, type and cumulation of adverse experiences.MethodsThe English Longitudinal Study of Ageing measured adverse life experiences in a life history interview. Cox proportional hazard models were used to investigate associations between dementia and three types of exposure: sum scores, individual experiences, and categories of similar experiences. We used linear hypothesis testing to assess whether associations between each experience and dementia differed significantly.ResultsA linear relationship between dementia and number of adult adverse experiences (HR:1.09, 95% CI:1.01-1.16), but not total or childhood experiences, was observed. When adverse experiences were considered separately, child abuse was associated with a 74% higher hazard of dementia (HR:1.74, 95% CI:1.25-2.43) and adult economic hardship was associated with a 32% higher hazard of dementia (HR:1.32, 95% CI:1.06-1.66). Associations between dementia and adverse experiences in childhood were heterogenous, showing greater variability than expected about a common hazard ratio (p = 0.01).ConclusionsAdulthood adverse experiences associate with dementia in a cumulative risk manner. In childhood, only abuse was associated with dementia. Use of sum scores to operationalize adverse experiences throughout the life-course may oversimplify associations with dementia. Both type and timing of experience influence the association. Work to prevent adverse experiences must span the life-course.},
}

@article {pmid41919773,
year = {2026},
author = {Tian, Q and Greig, EE and Hamwi, CM and An, Y and Resnick, SM and Ferrucci, L},
title = {Eye movement features are associated with cognitive and mobility decline.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261435981},
doi = {10.1177/13872877261435981},
pmid = {41919773},
issn = {1875-8908},
abstract = {BackgroundEye movement is a vital indicator of neurodegenerative diseases, brain health, and behavior. However, existing knowledge is limited to patient populations or cross-sectional samples. Little is known about eye movement in association with longitudinal cognitive and mobility decline in aging.ObjectiveInvestigate relationships between eye movement features with cognitive impairment, including Alzheimer's disease (AD), and longitudinal decline in cognition and mobility.MethodsIn 543 Baltimore Longitudinal Study of Aging participants (mean age = 71 years), we examined associations of eye movements with cognitive impairment of any severity, vascular conditions, and falls using logistic regression, and up to 18-year longitudinal changes in cognition and mobility using linear mixed-effects models. Four eye movement features (saccade, smooth pursuit, vergence, optokinetic nystagmus) were derived from a portable eye-tracking perimeter (Neurolign Dx100) using machine learning Least Absolute Shrinkage Selection Operator regression.ResultsHigher saccade, smooth pursuit, and vergence were bivariately or marginally associated with lower odds of cognitive impairment, including AD, and vascular diseases. In age- and sex-adjusted models, higher saccade was associated with slower declines in cognition (attention: Trail Making Test-Part A), mobility, and balance. Higher smooth pursuit was associated with slower decline in mobility and balance. Higher vergence was associated with slower cognitive decline (executive function: Trail Making Test-Part B; visuoperceptual speed: Digit Symbol Substitution Test). Higher optokinetic nystagmus was associated with lower odds of falls and slower decline in balance.ConclusionsSelect eye movement features may be indicators of age-related cognitive and mobility decline. Future studies are warranted to investigate underlying neuroimaging markers and brain pathology.},
}

@article {pmid41920139,
year = {2026},
author = {Islam, R and Dhaked, DK},
title = {Exploring natural phenolic compounds as amyloid-beta fibril inhibitors: computational insights for Alzheimer's disease.},
journal = {Journal of biomolecular structure & dynamics},
volume = {44},
number = {6},
pages = {3048-3065},
doi = {10.1080/07391102.2024.2444427},
pmid = {41920139},
issn = {1538-0254},
mesh = {*Amyloid beta-Peptides/chemistry/antagonists & inhibitors/metabolism ; *Alzheimer Disease/drug therapy/metabolism ; Molecular Dynamics Simulation ; *Phenols/chemistry/pharmacology ; Molecular Docking Simulation ; Humans ; Hydrogen Bonding ; Protein Binding ; Thermodynamics ; *Biological Products/chemistry/pharmacology ; },
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder and remains one of the leading causes of death in older age. While there is no direct cure for AD, very few FDA-approved drugs are available for managing the symptoms by targeting traditional targets. Amyloid-beta (Aß) peptides were identified as a crucial target for AD therapy, in recent times, phenolic compounds have shown the potential to inhibit Amyloid-beta peptide. These phenolic compounds destabilize Aß aggregation, but their inhibition mechanisms are not clearly understood. In this study, we thoroughly explored the molecular binding mechanism of >1000 phenolic compounds with the Aß fibrils via extra precision (XP) and induced fit docking (IFD) methods. Additionally, molecular dynamics (MD) simulations of the top 10 druglike phenolic compounds were performed with a simulation time of 500 nanoseconds (ns). Our results showed that two promising compounds, Rhapontigenin and Okanin, exhibited superior binding free energy and stability compared to the reference apigenin. These compounds effectively disrupted the Asp23-Lys28 salt bridge interactions and hydrogen bond patterns in the Aß fibril. Furthermore, both the identified compounds showed significant van der Waal's interaction with the Aß fibril. Our findings align with the previous studies and provide additional insights into inhibitory mechanisms at the molecular level. Additionally, this study incorporates analysis of non-covalent interactions and DFT studies to further elucidate the mechanisms. Nevertheless, it is crucial to emphasize that these results are based on in silico analyses and necessitate further experimental validation through in vitro and in vivo studies to confirm their efficacy.},
}

*Amyloid beta-Peptides/chemistry/antagonists & inhibitors/metabolism
*Alzheimer Disease/drug therapy/metabolism
Molecular Dynamics Simulation
*Phenols/chemistry/pharmacology
Molecular Docking Simulation
Humans
Hydrogen Bonding
Protein Binding
Thermodynamics
*Biological Products/chemistry/pharmacology

@article {pmid41920173,
year = {2026},
author = {Sanchez Mendez, J and Queme, B and Fu, Y and Morrison, JL and Lewinger, JP and Kawaguchi, ES and Mi, H and Obón-Santacana, M and Moratalla-Navarro, F and Martín, V and Moreno, V and Qu, C and Huyghe, JR and Newcomb, PA and Phipps, AI and Thomas, CE and Conti, DV and Wang, J and Platz, EA and Visvanathan, K and Keku, TO and Newton, CC and Um, CY and Kundaje, A and Gunter, MJ and Dimou, N and Papadimitriou, N and van Duijnhoven, FJB and Männistö, S and Rennert, G and Wolk, A and Hoffmeister, M and Brenner, H and Tian, Y and Le Marchand, L and Bouras, E and Tsilidis, KK and Bishop, DT and Maclnnis, RJ and Buchanan, DD and Ulrich, CM and Peoples, AR and Pellatt, A and Li, L and Devall, MA and Albanes, D and Berndt, SI and Gruber, SB and Ruiz-Narvaez, E and Song, M and Drew, DA and Chan, AT and Giannakis, M and Hsu, L and Peters, U and Stern, MC and Gauderman, WJ},
title = {TGF-β-pathway-based polygenic risk score modifies the association between red meat intake and colorectal cancer risk: Application of a novel pathway-based PRS method.},
journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},
volume = {},
number = {},
pages = {},
doi = {10.1158/1055-9965.EPI-25-1754},
pmid = {41920173},
issn = {1538-7755},
abstract = {BACKGROUND: Red and/or processed meat are established colorectal cancer (CRC) risk factors. Genome-wide association studies (GWAS) have reported over 200 variants associated with CRC risk. We used functional annotation data to identify subsets of variants within known pathways to construct pathway-based Polygenic Risk Scores (pPRS) to assess interactions with meat intake.

METHODS: A pooled sample of 30,812 cases and 40,504 CRC controls from 27 studies were analyzed. Quantiles for red and processed meat intake were constructed. 204 GWAS variants were annotated to genes with AnnoQ and assessed for overrepresentation in PANTHER-reported pathways. pPRS's were constructed from significantly overrepresented pathways. Covariate-adjusted logistic regression models evaluated interactions between pPRS and red or processed meat intake in relation to CRC risk.

RESULTS: A total of 30 variants were overrepresented in four pathways: Presenilin-Alzheimer disease, Cadherin/WNT-signaling, Gonadotropin-releasing hormone receptor, and TGF-β signaling. We found a significant interaction between TGF-β-pPRS and red meat intake (ORint = 0.95; 95% CI = 0.92-0.98; p = 0.003). When variants in the TGF-β pathway were assessed, we observed significant interactions of red meat with rs2337113 (intron SMAD7 gene, Chr18), and rs2208603 (intergenic region BMP5, Chr6) (p = 0.0005 & 0.036, respectively). There was no evidence of pPRS x red meat interactions for other pathways or with processed meat Conclusions:This pathway-based interaction analysis revealed a statistically significant interaction between variants in the TGF-β pathway and red meat consumption that impacts CRC risk.

IMPACT: These findings shed light into the possible mechanistic link between red meat consumption and CRC risk.},
}

@article {pmid41920384,
year = {2026},
author = {Liu, S and Yan, J and Dong, J},
title = {Curcumin and Glycyrrhiza glabra Synergistically Attenuate Alzheimer's Pathology via TLR4/NF-κB-Mediated Anti-inflammatory and Redox Modulation in a D-Gal/Sodium Nitrite-Induced Mouse Model.},
journal = {Neurochemical research},
volume = {51},
number = {2},
pages = {},
pmid = {41920384},
issn = {1573-6903},
support = {S202204140010//Research Project on Traditional Chinese Medicine, Wuhan Municipal Health and Family Planning Commission, Hubei Province/ ; },
mesh = {Animals ; *Curcumin/therapeutic use/pharmacology ; *Alzheimer Disease/drug therapy/chemically induced/metabolism/pathology ; Toll-Like Receptor 4/metabolism ; NF-kappa B/metabolism ; Mice, Inbred C57BL ; Mice ; *Glycyrrhiza/chemistry ; Male ; Drug Synergism ; Disease Models, Animal ; *Anti-Inflammatory Agents/pharmacology/therapeutic use ; Neuroprotective Agents/pharmacology/therapeutic use ; Oxidation-Reduction/drug effects ; },
abstract = {This study investigates the early synergistic effects of curcumin and licorice through vertical cooperation, which can simultaneously target both the upstream and downstream components of neuroinflammation. It evaluates their neuroprotective effects and potential mechanisms in a D-galactose/sodium nitrite-induced Alzheimer's disease mouse model.Eighty C57BL/6 mice were divided into eight groups (n = 10): wild-type (WT), AD model, curcumin monotherapy (AD + CL, 100 mg/kg), G. glabra monotherapy (AD + GG, 100 mg/kg), low-dose combination (AD + COM-L, 50 + 50 mg/kg), high-dose combination (AD + COM-H, 100 + 100 mg/kg), donepezil (3 mg/kg), and SN50 (NF-κB inhibitor, 400 µg/kg). Cognitive function was assessed via Morris Water Maze in WT, AD, AD + CL, AD + GG, and AD + COM-H groups, while all groups underwent molecular analyzes. The high-dose combination most effectively restored spatial memory, reducing escape latency by ~ 43% versus monotherapies. Molecularly, it synergistically reduced tau-related proteins (MAPT, GSK-3β) and suppressed the TLR4/MyD88/NF-κB axis, lowering inflammatory mediators (IL-6, TNF-α, CXCL1, PTGS2). IL-6 was further reduced by 28.6% and 40.0% compared to curcumin and G. glabra alone, respectively. The combination also enhanced antioxidant defense (increased SOD) and anti-apoptotic capacity (upregulated BCL-2) while reducing oxidative lipid damage (lower MDA). Network pharmacology identified 40 shared AD targets, with enrichment in NF-κB and IL-17 pathways, validated experimentally. In conclusion, curcumin and G. glabra exert synergistic neuroprotection by concurrently inhibiting the TLR4/NF-κB pathway and modulating IL-17 signaling, with G. glabra potentially targeting the TLR4/HMGB1 axis and curcumin directly inhibiting NF-κB activation, forming a complementary mechanistic interplay. This multi-target action disrupts the interplay between neuroinflammation and tau pathology, underscoring the combination's therapeutic potential for AD intervention.},
}

Animals
*Curcumin/therapeutic use/pharmacology
*Alzheimer Disease/drug therapy/chemically induced/metabolism/pathology
Toll-Like Receptor 4/metabolism
NF-kappa B/metabolism
Mice, Inbred C57BL
Mice
*Glycyrrhiza/chemistry
Male
Drug Synergism
Disease Models, Animal
*Anti-Inflammatory Agents/pharmacology/therapeutic use
Neuroprotective Agents/pharmacology/therapeutic use
Oxidation-Reduction/drug effects

@article {pmid41920402,
year = {2026},
author = {Güven, G and Gezegen, H and Şahin, E and Samancı, B and Hanağası, H and Gürvit, H and Alaylıoğlu, M and Gezen-Ak, D and Dursun, E and Bilgiç, B},
title = {Increased plasma soluble TREM2 levels in non-Alzheimer's dementia.},
journal = {Acta neurologica Belgica},
volume = {},
number = {},
pages = {},
pmid = {41920402},
issn = {2240-2993},
support = {TSA-2021-36356, TLO-2024-40878//Bilimsel Araştirma Projeleri Birimi, Istanbul Üniversitesi/ ; TSA-2021-36356, TLO-2024-40878//Bilimsel Araştirma Projeleri Birimi, Istanbul Üniversitesi/ ; TSA-2021-36356, TLO-2024-40878//Bilimsel Araştirma Projeleri Birimi, Istanbul Üniversitesi/ ; TSA-2021-36356, TLO-2024-40878//Bilimsel Araştirma Projeleri Birimi, Istanbul Üniversitesi/ ; TSA-2021-36356, TLO-2024-40878//Bilimsel Araştirma Projeleri Birimi, Istanbul Üniversitesi/ ; TSA-2021-36356, TLO-2024-40878//Bilimsel Araştirma Projeleri Birimi, Istanbul Üniversitesi/ ; TSA-2021-36356, TLO-2024-40878//Bilimsel Araştirma Projeleri Birimi, Istanbul Üniversitesi/ ; TSA-2021-36356, TLO-2024-40878//Bilimsel Araştirma Projeleri Birimi, Istanbul Üniversitesi/ ; TSA-2021-36356, TLO-2024-40878//Bilimsel Araştirma Projeleri Birimi, Istanbul Üniversitesi/ ; TSA-2021-36356, TLO-2024-40878//Bilimsel Araştirma Projeleri Birimi, Istanbul Üniversitesi/ ; },
}

@article {pmid41920501,
year = {2026},
author = {Xia, X and Eriksdotter, M and Clark, A and Brogaard, NJ and Gundgaard, J and Polavieja, P and Skajaa, N and Zetterberg, H and Kern, S and Skillbäck, TB and Jönsson, L},
title = {Utilization and Lifetime Costs of Formal Care for Alzheimer's Disease Dementia in Sweden.},
journal = {PharmacoEconomics},
volume = {},
number = {},
pages = {},
pmid = {41920501},
issn = {1179-2027},
support = {KI 4-3128/2022//Novo Nordisk A/S/ ; 2024-03599//Swedish Research Council/ ; 2023-00356//Swedish Research Council/ ; 2022-01018//Swedish Research Council/ ; 2019-02397//Swedish Research Council/ ; ALFGBG-1005471//ALF-agreement/ ; ALFGBG-965923//ALF-agreement/ ; ALFGBG-81392//ALF-agreement/ ; AF-939825//ALF-agreement/ ; 101053962//the European Union's Horizon Europe research and innovation programme/ ; ALFGBG-71320//Swedish State Support for Clinical Research/ ; 2019-02075//Swedish Research Council/ ; 2019-02075_15//Swedish Research Council/ ; FO2024-0097//Swedish Brain Foundation/ ; AF-842471//Alzheimerfonden/ ; AF-737641//Alzheimerfonden/ ; AF-92995//Alzheimerfonden/ ; AF-939825//Alzheimerfonden/ ; 2021-02680//VINNOVA/ ; 201809-2016862//Alzheimer's Drug Discovery Foundation/ ; ADSF-21-831376-C//AD Strategic Fund and the Alzheimer's Association/ ; ADSF-21-831381-C//AD Strategic Fund and the Alzheimer's Association/ ; ADSF-21-831377-C//AD Strategic Fund and the Alzheimer's Association/ ; ADSF-24-1284328-C//AD Strategic Fund and the Alzheimer's Association/ ; 22HLT07//the European Partnership on Metrology, co-financed from the European Union's Horizon Europe Research and Innovation Programme and by the Participating States/ ; 860197//the European Union's Horizon 2020 research and innovation programme/ ; JPND2021-00694//European Union Joint Programme-Neurodegenerative Disease Research/ ; UKDRI-1003//the National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre, the UK Dementia Research Institute at UCL/ ; 101112145//Innovative Health Initiative Joint Undertaking/ ; },
abstract = {INTRODUCTION: The study aimed to estimate the utilization and lifetime costs of formal care for individuals with Alzheimer's disease (AD) dementia in Sweden.

METHODS: We used longitudinal data from 20,366 individuals (mean age: 78.54 years) diagnosed with AD dementia from the Swedish Register of Cognitive/Dementia Disorders linked to other registers to derive data on formal care utilization, including inpatient and outpatient specialist care, prescribed drugs, and social care. We estimated formal care utilization across AD dementia stages defined by the Mini-Mental State Examination and the lifetime formal care costs (in 2023 Swedish krona, SEK) in patients with AD dementia using the Zhao and Tian estimator, which uses the inverse probability weighting technique to account for censoring due to loss to follow-up. The estimates of lifetime costs were compared with those of controls matched to patients with AD dementia by birth year, sex, and region of residence at the time of diagnosis.

RESULTS: The number of outpatient specialist visits decreased as AD severity increased, while the number of drug prescriptions and social care utilization increased with advancing AD stages. The estimated lifetime costs of formal care for AD dementia were 2,440,000 SEK (€212,174; $US230,189; 95% CI 2,088,000-2,793,000 SEK), compared with 510,000 SEK (€44,348; $US48,113; 95% CI 482,000-539,000 SEK) for matched controls.

CONCLUSIONS: This study estimated the utilization and lifetime costs of formal care for AD dementia using longitudinal register data. These findings will provide inputs for future economic evaluations of treatments and preventive interventions for AD dementia.},
}

@article {pmid41920507,
year = {2026},
author = {Lan, H and Zhang, J and Zhao, Z and Liu, X and Rao, C},
title = {Focal-DenseNet: A Risk Assessment Framework for Alzheimer's Disease in Heterogeneous MRI Data.},
journal = {Interdisciplinary sciences, computational life sciences},
volume = {},
number = {},
pages = {},
pmid = {41920507},
issn = {1867-1462},
support = {S202410497177//National Undergraduate Innovation and Entrepreneurship Training Program/ ; 25YJAZH138//Planning Fund Project of the Ministry of Education's Humanities and Social Sciences Research/ ; },
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disease of the nervous system, which has become an important public health issue attracting global attention. However, its exact causes and pathogenesis have not been fully elucidated, and the existing treatment methods and intervention measures have limited efficacy. Therefore, how to establish a scientific and efficient risk assessment mechanism has become the key to the prevention and treatment of AD. Aiming at this problem, this paper optimizes the convolutional neural network structure of DenseNet and proposes a Focal-DenseNet model that integrates the focal loss function for the risk assessment and diagnostic prediction of AD. First of all, preprocess the collected data to ensure the data quality for subsequent analysis. Secondly, establish the Focal-DenseNet model. Finally, use the model for training and testing. The test results show that the test set accuracy of the model reaches 98.98%, indicating that the model performs well. In addition, this paper also compares the proposed model with the DenseNet model without using the focal loss function and other common deep learning models (such as VGG16, ResNet, etc.). The results show that the model in this paper exhibits superiority in multiple performance indicators. In particular, it has achieved high scores in key indicators such as accuracy, AUC (the area under the receiver operating characteristic curve), precision, and recall. This study provides an efficient technical support for the early risk assessment of AD, and holds significant clinical application value and academic reference significance for improving the prevention and treatment level of AD and reducing the global public health burden.},
}

@article {pmid41920573,
year = {2026},
author = {Pathak, US and Mehralizade, A and Goldberg, TE and Zoghbi, AW},
title = {Dementia in Severe Schizophrenia.},
journal = {JAMA psychiatry},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamapsychiatry.2026.0171},
pmid = {41920573},
issn = {2168-6238},
abstract = {IMPORTANCE: Dementia develops in individuals with schizophrenia 4- to 20-fold more frequently than in the general population, but its etiology remains unexplained.

OBJECTIVE: To characterize the cognitive, clinical, and genetic features of dementia in individuals with severe, extremely treatment-resistant schizophrenia (SETRS).

This retrospective cohort study among individuals with SETRS was conducted at New York state hospitals from December 2017 through July 2019. All participants met DSM-5 schizophrenia criteria and were continuously hospitalized for 5 years or more. Exclusion criteria included forensic hospitalization, known medical causes of psychosis, or recent substance abuse. Cognitive, clinical, and genetic data were compared to data from individuals from the National Alzheimer Coordinating Center dataset, including those with Alzheimer disease (AD), frontotemporal dementia (FTD), Lewy body dementia (LBD), or vascular dementia (VD), along with healthy controls. Data were analyzed from January 2025 through December 2025.

MAIN OUTCOMES AND MEASURES: Multiple regression was used to analyze the effects of demographic, clinical, and genetic factors on the Montreal Cognitive Assessment (MoCA).

RESULTS: In this study's cohort of 155 individuals with SETRS (mean [SD] age, 59.3 [10.3] years; 56 female participants [36.1%]), 153 of 155 (98.7%) scored below the cutoff of 26 for mild cognitive impairment, and 73 of 155 (47.1%) scored below the cutoff of 10 for severe dementia (mean [SD] MoCA score, 9.8 [6.4]). At the item level, the MoCA profile of SETRS differed from those of AD and FTD but paralleled that of community-dwelling individuals with schizophrenia (Pearson r = 0.86; P < .001). No participants carried pathogenic variants in mendelian dementia genes; APOE4 allele frequency was significantly lower in SETRS (14.4%) than in AD (33.6%; odds ratio [OR], 0.33; 95% CI, 0.20-0.53; P < .001) or LBD (24.7%; OR, 0.51; 95% CI, 0.29-0.89; P = .01). Cognitive impairment was not attributable to premorbid intellectual disability, poor effort, medications, cardiometabolic risk factors, or institutionalization.

CONCLUSIONS AND RELEVANCE: In this cohort study of 155 individuals with SETRS, none of the commonly proposed explanations for schizophrenia dementia (eg, comorbid Alzheimer disease or cardiovascular risk factors) proved viable. The pattern of cognitive impairments differed from those of Alzheimer disease, frontotemporal dementia, and Lewy body dementia, but recapitulated and intensified that of community-dwelling schizophrenia.},
}

@article {pmid41920749,
year = {2026},
author = {Lu, Z and Fei, T and Yuequan, J and Chenguo, Y and Zhiqiang, W},
title = {DHCR24 Emerges as a Promising Target in Enhancing Cognitive Function.},
journal = {Current neuropharmacology},
volume = {},
number = {},
pages = {},
doi = {10.2174/011570159X421264260206063501},
pmid = {41920749},
issn = {1875-6190},
abstract = {INTRODUCTION: Against the backdrop of an aging global population, cognitive decline poses significant challenges to individuals' quality of life. Currently, therapeutic interventions for cognitive impairment, particularly in neurological disorders such as Alzheimer's Disease (AD), remain limited. DHCR24 (3β-dehydrocholesterol-Δ24-reductase), a cholesterol synthase, has been shown to exert neuroprotective effects in AD by mitigating oxidative stress. This study aims to delineate the specific molecular mechanisms through which DHCR24 influences cognitive learning function.

METHODS: A total of twenty mice were randomly assigned to either an experimental group or a control group. DHCR24 expression was pharmacologically downregulated, and synaptic plasticity was examined using slice patch-clamp recordings. Additionally, Barnes-Maze testing was performed to evaluate the role of DHCR24 in learning and memory functions. The influence of DHCR24 on endogenous neural stem cell differentiation was further analyzed by fluorescence immunohistochemistry.

RESULTS: The findings of this study demonstrated that U18666A effectively suppressed DHCR24 expression. This downregulation was associated with the inhibition of endogenous neural stem cell differentiation and a reduction in the expression of the synaptic AMPA receptor subunit GluA2. Consistent with these molecular changes, patch-clamp recordings revealed a corresponding attenuation of AMPA receptor-mediated synaptic plasticity. Behavioral assessments further corroborated that pharmacological inhibition of DHCR24 resulted in significant cognitive impairment in mice.

DISCUSSION: This study implicates DHCR24 as a key factor capable of modulating cognitive function, thereby offering a novel direction and potential intervention target for research on Alzheimer's disease and neurodegeneration.

CONCLUSION: DHCR24 represents a promising novel target for cognitive enhancement.},
}

@article {pmid41920750,
year = {2026},
author = {Mishra, D and Yadav, S},
title = {Preparation and Characterization of Insulin-loaded Polymeric Nanoparticles for Nasal Delivery.},
journal = {Current neurovascular research},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115672026437865260307135245},
pmid = {41920750},
issn = {1875-5739},
abstract = {INTRODUCTION: Intranasal delivery of insulin offers a promising non-invasive route to target the brain, particularly for neurodegenerative disorders like Alzheimer's disease (AD). However, challenges such as enzymatic degradation in the nasal cavity and limited mucosal absorption hinder therapeutic efficiency. This study aimed to develop and char-acterize chitosan-coated Polyethylene Glycol - Poly(lactic-co-glycolic acid) (PEG-PLGA) nanoparticles to enhance insulin delivery to the brain.

MATERIALS AND METHODS: PEG-PLGA copolymers were synthesized and confirmed using ^1HNMR spectroscopy. Insulin-loaded nanoparticles were prepared via the nanoprecipitation method and coated with chitosan to improve mucoadhesion. Formulations were optimized based on polymer- to-surfactant ratio, surfactant type, and drug concentration. Nanoparticles were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), and zeta potential analysis. In vitro drug release was evaluated in phosphate buffer (pH 7.4) over 48 hours. Cytotoxicity was assessed using MTT assays on human nasal epithelial cells.

RESULTS: The optimized PEG-PLGA: Tween-80 formulation (30:100) showed the highest entrapment efficiency (61.4 ± 2.38%), optimal particle size (182.2 ± 5.98 nm), and stable zeta potential (-9.08 ± 0.09 mV). Chitosan-coated nanoparticles demonstrated sustained insulin release over 48 hours, with reduced burst effect compared to uncoated or PVA-based formulations. TEM confirmed spherical morphology with smooth surfaces. In vitro cell viability ex-ceeded 90% across all formulations at concentrations up to 200 μg/mL, indicating good biocompatibility.

DISCUSSION: PEGylation and chitosan coating synergistically enhanced nanoparticle stability, drug encapsulation, and release control. Tween-80, due to its optimal hydrophilic-lipophilic balance, significantly improved entrapment and minimized early drug diffusion. The PEG shell provided steric hindrance, contributing to prolonged release, while chitosan further delayed release kinetics. These features collectively support enhanced delivery of insulin to the brain through the nasal route.

CONCLUSION: Cervical carotid stenosis severity alone does not predict functional compromise. Integrating VEP assessment with metabolic profiling-particularly HDL and HbA1c levels-may enhance risk stratification, offering a more comprehensive and individualized evaluation, especially in asymptomatic patients. This novel perspective links biochemical markers to electrophysiological integrity and collateral efficiency in ICA stenosis.Chitosan-coated PEG-PLGA nanoparticles, especially with Tween-80, provide a safe and effective platform for intranasal insulin delivery. The optimized formulation improves drug bioavailability and enables sustained release.},
}

@article {pmid41921123,
year = {2026},
author = {Bukhbinder, AS and Ling, Y and Jhin, L and He, E and Harris, K and Rodriguez, M and Thomas, J and Cruz, G and Phelps, K and Kim, Y and Chen, L and Jiang, X and Schulz, PE},
title = {Risk of Alzheimer Dementia After High-Dose vs Standard-Dose Influenza Vaccination.},
journal = {Neurology},
volume = {106},
number = {8},
pages = {e214782},
doi = {10.1212/WNL.0000000000214782},
pmid = {41921123},
issn = {1526-632X},
mesh = {Humans ; *Alzheimer Disease/epidemiology/prevention & control ; *Influenza Vaccines/administration & dosage ; Aged ; Female ; Male ; Retrospective Studies ; Aged, 80 and over ; *Vaccination ; Influenza, Human/prevention & control ; Cohort Studies ; },
abstract = {BACKGROUND AND OBJECTIVES: Previous studies, including large cohort analyses comparing vaccinated and unvaccinated adults, suggest that routine immunizations such as inactivated influenza vaccines (IIVs) may reduce Alzheimer dementia (AD) risk. Whether AD risk differs after high-dose IIV (H-IIV) vs standard-dose IIV (S-IIV) remains unexamined. We hypothesized that AD risk would be lower among adults ≥65 years after H-IIV compared with S-IIV.

METHODS: This retrospective cohort study analyzed data spanning 2014-2019 from IQVIA PharMetrics Plus for Academics, a US health care claims database. Eligible participants were ≥65 years with ≥2 years of continuous medical and pharmaceutical coverage and no previous diagnostic or pharmacotherapeutic indicators of cognitive impairment. Vaccinations were identified by name and Current Procedural Terminology codes. Participants were followed for up to 3 years postvaccination. Incident AD was defined using International Classification of Diseases codes and AD medication dispenses (anticholinesterase inhibitors, memantine). We emulated a target trial using sequential nested trials to align eligibility, treatment assignment, and time-zero with vaccination dates, preventing immortal time bias. Inverse probability weighting adjusted for measured confounding, emulated randomization, and mitigated selection bias. Effects were estimated as risk difference, number needed to treat (NNT), risk ratio; 95% CIs were obtained via bootstrapping. Secondary analyses examined potential effect modifiers such as sex.

RESULTS: The H-IIV group included 120,775 unique participants (185,183 person-trials; mean age 74.4 years, SD 5.5; 57.3% female), and the S-IIV group included 44,022 participants (53,918 person-trials; mean age 73.0, SD 6.1; 56.4% female). H-IIV was associated with significantly lower AD risk during months 1-25 postvaccination (minimum NNT = 185.2 at 25 months). After sex stratification, risk reduction persisted longer among women (months 1-13, minimum NNT = 416.7) than men (months 17-24, significant only in intention-to-treat analysis, minimum NNT = 232.6).

DISCUSSION: High-dose influenza vaccination is associated with reduced AD risk compared with standard-dose vaccination in adults ≥65 years, with a stronger effect among women. Significant study limitations included duration of follow-up (≤3 years) and lack of sociodemographic, lifestyle, biomarker, and mortality data. Further research is needed to clarify whether the observed difference reflects protection against influenza infection or non-infection-related mechanisms.

CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that treatment with H-IIV vs S-IIV was associated with decreased incident dementia in individuals ≥65 years of age captured in this US health care claims database.},
}

Humans
*Alzheimer Disease/epidemiology/prevention & control
*Influenza Vaccines/administration & dosage
Aged
Female
Male
Retrospective Studies
Aged, 80 and over
*Vaccination
Influenza, Human/prevention & control
Cohort Studies

@article {pmid41921130,
year = {2026},
author = {Falzarano, F and Greenfield, A and Mason, H and Bumbalova, K and Rojas, E and Bumbalov, A},
title = {A Mobile Self-Assessment and Referral Platform for Family Caregivers of Individuals With Alzheimer Disease and Related Dementias: Protocol for a Pilot Randomized Controlled Trial.},
journal = {JMIR research protocols},
volume = {15},
number = {},
pages = {e90244},
doi = {10.2196/90244},
pmid = {41921130},
issn = {1929-0748},
mesh = {Humans ; *Caregivers/psychology ; Pilot Projects ; *Alzheimer Disease/nursing/therapy/psychology ; *Referral and Consultation ; *Dementia/therapy ; *Mobile Applications ; Self Efficacy ; *Self-Assessment ; Randomized Controlled Trials as Topic ; Male ; Female ; Telemedicine ; },
abstract = {BACKGROUND: Family caregiving for individuals with Alzheimer disease and related dementias (ADRD) is characterized by increasing complexity, intensity, and demand across the disease trajectory. Formal home- and community-based services can provide knowledge, skills, and resources to enhance preparedness and self-efficacy, which may protect against adverse caregiving outcomes; however, awareness and uptake of these services remain low. As caregivers increasingly turn to the internet for information and support in their role, technology offers an opportunity to create a more seamless pipeline between assessment and service referral to match family caregivers with targeted services that meet their specific needs.

OBJECTIVE: The primary objective of this study is to evaluate the feasibility and acceptability of CarePair-a mobile self-assessment and service referral platform-among ADRD family caregivers. Secondary objectives are to assess the preliminary efficacy of CarePair in reducing stress, depressive symptoms, and anxiety, and enhancing self-efficacy among caregivers randomized to the intervention versus an attention control condition. This study also aims to generate preliminary effect size estimates to inform sample size calculations for a future fully powered randomized controlled trial (RCT).

METHODS: This pilot RCT will evaluate the feasibility, acceptability, and preliminary efficacy of CarePair. Eighty ADRD family caregivers will be enrolled and randomized in a 1:1 ratio to the intervention (n=40) or an attention control condition (n=40). Recruitment will be facilitated by the project study site located in an urban metropolitan area of the United States, targeting participants who report residing in and/or being in close proximity to any of the following locations: New York City, Long Island, and Westchester County, New York; Seattle, Washington; and Los Angeles, California. Primary feasibility outcomes include recruitment, retention, and completion rates; website usability; and intervention satisfaction. Exploratory analyses will assess preliminary efficacy on stress, depressive and anxiety symptoms, and self-efficacy.

RESULTS: This trial was funded by the National Institute on Aging in September 2023 and received approval from the institutional review board of the University of Southern California on September 10, 2025. Recruitment began in September 2025 and is scheduled to conclude in May 2026, with data collection scheduled to end in August 2026. As of February 2026, 44 participants have been enrolled and 22 have completed the study.

CONCLUSIONS: This pilot trial will offer foundational evidence regarding the feasibility and acceptability of the CarePair intervention. Study findings will determine if "go" criteria are met to warrant the advancement to a larger-scale efficacy trial. Participant insights will also be used to guide intervention refinements and digital platform optimization. By offering a low-burden, caregiver-centered mobile app, CarePair has the potential to facilitate and streamline the timely identification of needs and referral to relevant services for ADRD family caregivers.},
}

Humans
*Caregivers/psychology
Pilot Projects
*Alzheimer Disease/nursing/therapy/psychology
*Referral and Consultation
*Dementia/therapy
*Mobile Applications
Self Efficacy
*Self-Assessment
Randomized Controlled Trials as Topic
Male
Female
Telemedicine

@article {pmid41921136,
year = {2026},
author = {Basapur, S and Gellman, C and Plenge, JB and Troutman, A and Yurko, E and Woolsey, B and McClendon, J and Marceau, L and Aggarwal, NT},
title = {From Bottles to Home Care System: Feasibility of a Comprehensive Self-Medication Management System to Reduce Medication Errors in Dementia.},
journal = {JMIR human factors},
volume = {},
number = {},
pages = {},
doi = {10.2196/86828},
pmid = {41921136},
issn = {2292-9495},
abstract = {BACKGROUND: Medication adherence is a critical challenge for people living with dementia (PLwD) and their caregivers. Standard care relies on appropriate medication management, yet there are few effective options for PLwD beyond manual pill counting approaches and caregiver administrated dosing. These methods are prone to errors and impose significant burden. Technologically enhanced adherence tools include smart caps, reminder apps, and electronic dispensers which have improved tracking and provided basic alerts, but continue to depend on manual interaction, lack integration with clinical systems, and are often unsuitable for individuals with cognitive decline. The HiDO Home Care System is a artificial intelligence (AI) enabled self-medication device (SMD), advancing the field by removing manual pill counting, automating chain-of-custody, verifying consumption, and logging medication adherence through neuroscience-based logic and real-time monitoring.

OBJECTIVE: This study evaluated the feasibility, usability, and performance of the HCS for at-home medication management in dyads of PLwD and their caregivers. We specifically examined set up, accuracy of dispensing medication, efficiency of task completion, and satisfaction with the device.

METHODS: A pooled analysis usability study was conducted with 35 caregiver-patient dyads at Rush University Medical Center. Pooled analysis combined two sequential in-clinic usability cohorts run at different time points with the same protocol. Participants were recruited from the Rush Memory Clinic and Rush Alzheimers Disease Center data repository. Participant dyads completed device set up, medication dispensing, and simulated medication use using the system's automated logging and dual-camera verification. Dyads repeated dispensing and simulated medication use following automated reminders sent to their mobile device. Dyads were encouraged to repeat dispensing tasks multiple time. Quantitative measures included time to set-up the device, time from reminder to dispensation, number of successful attempts, and device reliability and system usability scores (SUS). Qualitative measures captured caregiver perceptions of usability, acceptability, and burden.

RESULTS: All 35 dyads successfully completed at least one dispensing task using the HCS. The average time for the first dispense attempt was 1:41 minutes (n=35). The second attempt averaged 1:35 minutes (n=21). Attempt 3 averaged 2:03 minutes (n=6). The system maintained accuracy across all users, with some variability in timing across age groups. The HCS received an overall mean System Usability Scale (SUS) score of 70.2 (n=34) reflecting above average usability of the device. Caregivers reported access to a system like HCS could reduce stress associated with medication administration and recommended improvements to specific design elements.

CONCLUSIONS: The HCS demonstrated early feasibility, accuracy, and usability as an advanced SMD tailored to the unique needs of PLwD. By automating the medication safety chain from delivery through consumption, HCS reduces caregiver workload and enhances patient safety and medication management. These findings support HCS as a viable medication adherence solution, addressing limitations of prior devices and enabling better dementia care. Larger-scale, longitudinal studies are planned to examine clinical outcomes, caregiver burden, and cost-effectiveness within real-world home and community settings.},
}

@article {pmid41921240,
year = {2026},
author = {Miller, LM and Ozgur, H and Luna, LP},
title = {Limbic neurodegenerative disease: How radiologists can identify a common but underdiagnosed cause of dementia.},
journal = {European journal of radiology},
volume = {199},
number = {},
pages = {112828},
doi = {10.1016/j.ejrad.2026.112828},
pmid = {41921240},
issn = {1872-7727},
abstract = {Limbic-predominant Age-related TDP-43 Encephalopathy (LATE) is a pathology-based diagnosis which represents an increasingly recognized but substantially underappreciated cause of dementia in older adults, potentially accounting for 15-25% of cases clinically diagnosed as Alzheimer's Disease. Limbic-predominant Amnestic Neurodegenerative Syndrome (LANS) is an overlapping proposed clinical diagnosis based on functional patterns of limbic-predominant neurodegeneration. This educational review examines the pathologic basis, clinical presentation, and multimodal imaging features of LATE and LANS, with emphasis on the role of radiology in the diagnostic algorithm. Both entities are characterized by relatively late presentation and an indolent course of progressive memory loss. Two diagnostic frameworks are presented: the NIA-AA ATN-based approach utilizing amyloid and tau biomarkers to establish "probable" or "possible" LATE diagnoses, and the Mayo Clinic LANS framework emphasizing functional neuroimaging to elucidate patterns of neurodegeneration. As targeted therapies improve, more accurate diagnosis is becoming increasingly important for appropriate patient selection, prognostic counseling, and future targeted therapeutic trials. Radiologists play an essential role in recognizing the characteristic imaging phenotype and raising clinical awareness of LATE and LANS.},
}

@article {pmid41921372,
year = {2026},
author = {Si, W and Ma, X and Lin, J and Xu, T and Wang, R and Zhu, A and Cao, W},
title = {Development and validation of an eye-tracking-based cognitive impairment screening system for older adults in China: a cross-sectional study.},
journal = {International journal of medical informatics},
volume = {214},
number = {},
pages = {106412},
doi = {10.1016/j.ijmedinf.2026.106412},
pmid = {41921372},
issn = {1872-8243},
abstract = {BACKGROUND: Global population ageing has rendered cognitive impairment a critical public health issue. Early screening is essential for timely intervention; however, traditional tools are limited by their reliance on professionals, cultural and educational biases, and high cost.

PURPOSE: This study aimed to develop and validate an unobtrusive, eye-tracking-based cognitive screening system (CIS-ET) for older adults in China, evaluating its efficacy in distinguishing between healthy controls (HCs), mild cognitive impairment (MCI), and Alzheimer's disease (AD).

METHODS: In this cross-sectional study, 113 participants (41 HCs, 41 with MCI, and 31 with AD) were recruited in Shanghai. All participants completed the CIS-ET (assessing 6 cognitive domains via 43 items), the Mini-Mental State Examination (MMSE), and the Montreal Cognitive Assessment (MoCA). Statistical analyses included receiver operating characteristic (ROC) curve analysis, partial correlation, and Cronbach's α for reliability.

RESULTS: The CIS-ET demonstrated excellent discriminative validity. The area under the curve (AUC) for distinguishing HCs from participants with MCI was 0.878 (95% CI: 0.796 to 0.959), with a sensitivity of 85.37% and specificity of 87.80%. For differentiating MCI from AD, the AUC was 0.893 (95% CI: 0.821 to 0.965; sensitivity 77.42%, specificity 87.80%). When distinguishing HCs from the combined cognitive impairment group (MCI + AD), the AUC reached 0.927 (95% CI: 0.876 to 0.978; sensitivity 91.67%, specificity 87.80%). After adjusting for age and education, the CIS-ET total score showed strong positive correlations with MMSE (r = 0.870, p < 0.001) and MoCA (r = 0.891, p < 0.001). Internal consistency reliability was acceptable (Cronbach's α = 0.685).

CONCLUSIONS: The CIS-ET is a valid, reliable, and user-friendly tool for the early screening of cognitive impairment in older adults in China. Its design supports potential for large-scale use in community healthcare settings. (Trial registration: Chinese Clinical Trial Registry, ChiCTR2400085172.).},
}

@article {pmid41921464,
year = {2026},
author = {Catino, F and Castellana, F and Zupo, R and Giannoccaro, V and Lampignano, L and Petrosillo, AM and Addabbo, F and Sborgia, G and Colacicco, G and Santoro, C and Boero, G and Impedovo, D and Zheng, Y and Sardone, R},
title = {Multimodal biomarker AI techniques for early neurocognitive disorder diagnosis: A systematic review.},
journal = {Artificial intelligence in medicine},
volume = {177},
number = {},
pages = {103389},
doi = {10.1016/j.artmed.2026.103389},
pmid = {41921464},
issn = {1873-2860},
abstract = {BACKGROUND: Early diagnosis of Alzheimer's disease (AD) and related dementias remains challenging because no single biomarker sufficiently captures the complex and multifactorial nature of the underlying pathology. In recent years, multimodal artificial intelligence (AI) models capable of integrating heterogeneous data sources-such as neuroimaging, fluid biomarkers, genetics, and cognitive assessments-have emerged as a promising strategy to improve early detection and risk stratification.

METHODS: We performed a PRISMA-guided systematic review (PROSPERO: CRD420251049848) of studies published from 2010 to 2025. We included 27 peer-reviewed studies applying AI/ML to ≥2 biomarker modalities for diagnostic classification or prognostic prediction (e.g., MCI-to-AD conversion), with an explicit emphasis on multimodal designs that incorporated at least one minimally invasive and/or widely deployable modality (e.g., cognitive tests, blood-based biomarkers, APOE/genetics, retinal imaging, or routine clinical features). Risk of bias was assessed using QUADAS-2.

RESULTS: Across the 27 included studies, multimodal AI models generally outperformed the best unimodal baselines, particularly when combining complementary biological information (e.g., imaging with molecular or clinical features). Diagnostic tasks more often achieved high discrimination (frequently AUCs in the ~0.85-0.95 range under internal validation), whereas prognostic prediction-especially MCI-to-AD conversion-remained more challenging (typically ~0.75-0.85 AUC in the best-performing models). However, evidence for generalizability was limited, as external validation was uncommon and QUADAS-2 frequently highlighted concerns in the Index Test domain related to overfitting risk and incomplete validation.

DISCUSSION: Overall, multimodal AI provides a more comprehensive representation of AD/MCI-related pathology than unimodal approaches and can improve early diagnostic classification and, to a lesser extent, prognostic prediction. However, translation to clinical practice is still constrained by limited external validation and heterogeneous reporting, which hamper generalizability and clinical trust. Future work should prioritize prospective multi-center studies, robust external validation, and transparent reporting (including interpretability analyses) to support real-world deployment.},
}

@article {pmid41921527,
year = {2026},
author = {Wang, Y and Ma, X and Zou, Y and Wang, T and Chu, S and Mao, C and Yu, S and Gao, J and Qiu, L},
title = {Comparison of the analytical and clinical performance of three immunoassay platforms for plasma glial fibrillary acidic protein in Alzheimer's disease.},
journal = {Clinical chemistry and laboratory medicine},
volume = {},
number = {},
pages = {},
pmid = {41921527},
issn = {1437-4331},
abstract = {OBJECTIVES: This study aimed to compare the analytical and clinical performance of plasma glial fibrillary acidic protein (GFAP) across three immunoassay platforms.

METHODS: Plasma GFAP was measured on three immunoassay platforms (Simoa HD-X, Maccura i1000, MS-Fast Pro 160) in 302 participants from the Peking Union Medical College Hospital dementia cohort (139 Alzheimer's disease dementia [ADD], 116 non-AD dementia [NADD]). Inter-platform agreement was assessed using Passing-Bablok regression, Bland-Altman analysis, and Spearman correlation. ROC analyses and multimarker models on the Simoa platform were used to evaluate GFAP, NfL, a core plasma panel (Aβ1-42, p-tau181, p-tau217), and their combinations.

RESULTS: Plasma GFAP levels were significantly higher in ADD than in NADD across all three platforms. Inter-platform correlations were strong (Spearman's r=0.874-0.932), but Passing-Bablok regression showed substantial proportional bias and systematically higher concentrations on the Simoa platform. ROC-based discrimination between ADD and NADD was comparable across platforms (AUC 0.732-0.740), whereas assay-specific optimal cut-offs differed markedly. On the Simoa platform, GFAP alone achieved an AUC of 0.731. The core plasma panel (Aβ1-42, p-tau181, p-tau217) achieved an AUC of 0.898, which increased to 0.924 after adding GFAP and NfL.

CONCLUSIONS: This study provides a comparison of plasma GFAP measurements across three immunoassay platforms, revealing strong correlations but substantial differences in absolute values and decision cut-offs. The clinical analyses show that similar discriminative performance can coexist with markedly different platform-specific cut-offs, underscoring the need for platform-specific cut-offs and further harmonization of GFAP measurements.},
}

@article {pmid41921847,
year = {2026},
author = {Dong, YR and Wang, JR and Yang, Y and Chen, QZ and Jiang, YQ and Yang, X and Zhou, MC and Cao, SP and Zeng, SX and Zang, CX and Li, FF and Bao, XQ and Zhang, D},
title = {Unveiling the UFMylation Pathway: Implications in neurodegenerative diseases.},
journal = {Journal of molecular biology},
volume = {},
number = {},
pages = {169772},
doi = {10.1016/j.jmb.2026.169772},
pmid = {41921847},
issn = {1089-8638},
abstract = {UFMylation is a recently characterized post-translational modification (PTM) system that conjugates Ubiquitin-Fold Modifier 1 (UFM1) to target proteins via a dedicated enzymatic cascade. This modification system regulates critical cellular processes by controlling protein subcellular localization, modulating protein-protein interactions, and coordinating with ubiquitination to regulate protein stability. Emerging evidence highlights UFMylation as a critical modifier of pathological proteins, including tau and α-synuclein, while impaired UFMylation pathways are observed in the brains of individuals with neurodegenerative disorders. In this review, we summarize the current role and mechanism of UFMylation in the pathogenesis of neurodegenerative diseases, offering the first comprehensive framework for targeting UFMylation in the treatment of neurodegenerative diseases.},
}

@article {pmid41921869,
year = {2026},
author = {Manoharan, SD and Usman, AHS and Nassir, CMNCM and Hamid, HA and Hashim, NFM and Norazit, A and Murthy, J and Hein, ZM and Zainol, M and Chiroma, SM and Mustapha, M and Moklas, MAM and Mehat, MZ},
title = {Ficus deltoidea attenuates tau hyperphosphorylation and neurodegeneration in a D-galactose and aluminum-induced Alzheimer's disease-like rat model.},
journal = {Behavioural brain research},
volume = {},
number = {},
pages = {116197},
doi = {10.1016/j.bbr.2026.116197},
pmid = {41921869},
issn = {1872-7549},
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by cognitive decline, neuronal loss and abnormal tau phosphorylation. Although aluminum exposure has been suggested as a risk factor, no causal link to AD has been confirmed. The combination of D-galactose and aluminum chloride (AlCl3) is widely used to model aging-related neurotoxicity, including oxidative stress, cognitive impairment and tau hyperphosphorylation. Ficus deltoidea (FD), a Southeast Asian plant rich in flavonoids like vitexin, exhibits antioxidant and anti-inflammatory properties, but its role in tau pathology remains unclear. In this study, male Wistar rats received D-galactose/AlCl3 to induce AD-like pathology and were co-treated with FD extract (50, 100, or 200mg/kg) and donepezil. The results showed that FD significantly improved spatial memory, reduced hippocampal neuronal loss and attenuated p-tau T181 levels. The apparent decrease in p-tau levels may have led to reduced neurodegeneration and improved learning and memory. These findings support FD's neuroprotective potential against aluminum-induced tauopathy and warrant further studies in translational AD-like models.},
}

@article {pmid41921971,
year = {2026},
author = {Masquelier, E and Hicks, M and Watkins, N and Lim, N and Yi, J and Morse, DE and Sepunaru, L and Gordon, MJ},
title = {Electric Double Layer Phenomena Near Surfaces Irreversibly Trigger Assembly of Tau Protein.},
journal = {Journal of the American Chemical Society},
volume = {},
number = {},
pages = {},
doi = {10.1021/jacs.5c23171},
pmid = {41921971},
issn = {1520-5126},
abstract = {The reversible folding and assembly of the human brain protein tau are regulated by charge neutralization through limited and reversible phosphorylation, enabling tau to bind tubulin and maintain the structural integrity of neuronal microtubules. However, in neurodegenerative diseases like Alzheimer's and related tauopathies, tau becomes hyperphosphorylated, detaches from tubulin, and irreversibly assembles into β-structured amyloid filaments responsible for neuronal death. In previous work, we showed that charge neutralization via Faradaic electroreduction of cationic residues in tau and other intrinsically disordered proteins can mimic phosphorylation to trigger protein condensation, folding, and assembly. Here, we demonstrate that even non-Faradaic effects─including large electric fields and concentration gradients in the electric double layer, together with spatial ordering of ions at the solution-electrode interface─can induce folding and assembly of tau, its microtubule-binding region K18, and a 19-residue tau peptide (jR2R3 P301L) containing a mutation known to induce early aggregation in vitro and in vivo. Assembly occurs on different electrode materials at identical effective electric fields, demonstrating independence from the electrode hydrophobicity and electronic structure. Surface-enhanced infrared absorption and plasmon resonance spectroscopies show that near-surface electric fields of ∼1 MV/cm trigger K18 folding and assembly. Ion ordering and charge screening near electrodes at higher salt concentrations (50 vs 1 mM) also reduce Coulombic repulsion between protein monomers and their cationic residues, promoting folding and assembly. Overall, these results show that interfacial electric fields and other non-Faradaic processes can reveal and drive protein misfolding and aggregation, hallmarks of tauopathies and prion-related neurodegenerative diseases.},
}

@article {pmid41922169,
year = {2026},
author = {Hobby, EL and Weber, AJ and Liu, E and Hurst, C and Greathouse, KM and Gaiteri, C and Seyfried, NT and Herskowitz, JH},
title = {A Multi-Network Approach Identifies Proteins Related to Dendritic Spines in Alzheimer's Disease.},
journal = {eNeuro},
volume = {},
number = {},
pages = {},
doi = {10.1523/ENEURO.0468-25.2026},
pmid = {41922169},
issn = {2373-2822},
abstract = {Proteomic studies have generated robust assessments of protein abundance changes in Alzheimer's disease (AD); however, identifying how the protein abundance changes affect specific biological processes remains a challenge. To address these hurdles, we used a multi-network computational analysis approach that integrated dendritic spine morphometry data with mass spectrometry-based proteomics from the same individuals. The samples exhibited a range of AD neuropathology and were categorized into three groups: controls, asymptomatic AD, and AD cases. Multiplex tandem mass tag mass spectrometry proteomic data (N = 8,212 proteins) was generated on Brodmann area 46 (BA46) dorsolateral prefrontal cortex (DLPFC) human samples (N = 41, 23 males and 18 females), from which dendritic spine morphometry analysis existed. To integrate the multi-scale data types, two computational network analysis methods were performed, including WeiGhted co-expression network analysis (WGCNA) and SpeakEasy2 (SE2). Both WGCNA and SE2 revealed that the mitochondria protein modules were decreased in AsymAD and AD cases compared to controls, whereas the DNA repair modules were increased in AsymAD and AD compared to controls. Synaptic protein modules that correlated to multiple spine morphology traits were identified in both WGCNA and SE2. Pearson correlation analyses identified over a dozen individual proteins linked to multiple dendritic spine density and morphology traits. Collectively, these findings demonstrate how integration of spine morphometry data with proteomics can contextualize proteins for functional validation and identify synaptic alterations in AD progression.Significance Statement Cognitive decline in Alzheimer's disease associates more strongly with synapse and dendritic spine loss than amyloid-beta or tau pathology. However, one in three individuals harbor Alzheimer's disease neuropathology at death but were cognitively indistinguishable from baseline in life. Preservation of spines and synapses is hypothesized to prevent cognitive decline in these individuals. Identifying the molecular drivers of synaptic changes in Alzheimer's disease could yield deeper understanding of disease progression. Here, we utilized two computational network approaches that integrated multi-scale data, including proteomics and dendritic spine morphometry from the same humans, to identify proteins relevant to synapses in Alzheimer's disease. Hundreds of proteins related to mitochondria, DNA repair, and synaptic signaling were associated with alterations in synapse structure and function in Alzheimer's disease.},
}

@article {pmid41922206,
year = {2026},
author = {Guney, T and Altin, S and Dikici, E and Isik, M and Koksal, E},
title = {Folliculi sennae Extract: A Multifunctional Approach to Alzheimer's and Diabetes.},
journal = {Journal of oleo science},
volume = {75},
number = {4},
pages = {455-464},
doi = {10.5650/jos.ess25242},
pmid = {41922206},
issn = {1347-3352},
mesh = {*Alzheimer Disease/drug therapy ; *Plant Extracts/pharmacology/therapeutic use/chemistry/isolation & purification ; Antioxidants/pharmacology/isolation & purification ; *Diabetes Mellitus, Type 2/drug therapy ; *Hypoglycemic Agents/pharmacology/isolation & purification ; Cholinesterase Inhibitors/pharmacology/isolation & purification ; Gallic Acid/isolation & purification/pharmacology/analysis ; Glycoside Hydrolase Inhibitors/pharmacology/isolation & purification ; Humans ; Oxidative Stress/drug effects ; Neuroprotective Agents/pharmacology/isolation & purification ; Quercetin/isolation & purification/pharmacology ; Kaempferols/isolation & purification/pharmacology/analysis ; Luteolin/isolation & purification ; Tandem Mass Spectrometry ; Phenols ; },
abstract = {Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) exhibit overlapping molecular pathways characterized by oxidative imbalance and enzyme dysfunction. This study provides a comprehensive evaluation of the multifunctional potential of Folliculi sennae (F. sennae) ethanol extract as a natural therapeutic agent targeting these disorders. Phenolic profiling using LC-MS/MS revealed abundant bioactive compounds, including quercetin, luteolin, kaempferol, and gallic acid, with high linearity and reproducibility. The extract exhibited moderate antioxidant activity across DPPH, ABTS, FRAP, and CUPRAC assays, highlighting its redox-modulating capacity. Importantly, enzyme inhibition assays demonstrated notable inhibition of acetylcholinesterase (AChE, IC50 = 10.34 µg/mL), butyrylcholinesterase (BChE, IC50 = 7.72 µg/mL), and α-glucosidase (IC50 = 6.66 µg/mL), indicating potential neuroprotective and antidiabetic effects. These findings suggest that F. sennae orchestrates a synergistic interplay between antioxidant defense and targeted enzymatic inhibition, positioning it as a promising multitarget natural candidate for managing oxidative stress-linked neurodegenerative and metabolic disorders. The study lays the biochemical groundwork for future translational research exploring F. sennae as a safe, plant-based therapeutic intervention.},
}

*Alzheimer Disease/drug therapy
*Plant Extracts/pharmacology/therapeutic use/chemistry/isolation & purification
Antioxidants/pharmacology/isolation & purification
*Diabetes Mellitus, Type 2/drug therapy
*Hypoglycemic Agents/pharmacology/isolation & purification
Cholinesterase Inhibitors/pharmacology/isolation & purification
Gallic Acid/isolation & purification/pharmacology/analysis
Glycoside Hydrolase Inhibitors/pharmacology/isolation & purification
Humans
Oxidative Stress/drug effects
Neuroprotective Agents/pharmacology/isolation & purification
Quercetin/isolation & purification/pharmacology
Kaempferols/isolation & purification/pharmacology/analysis
Luteolin/isolation & purification
Tandem Mass Spectrometry
Phenols

@article {pmid41922490,
year = {2026},
author = {Holmes, SE and Smith, GS},
title = {Trajectories of late-life depression: insights from molecular imaging.},
journal = {Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology},
volume = {},
number = {},
pages = {},
pmid = {41922490},
issn = {1740-634X},
support = {R01NS125482//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; R01AG059390//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; },
abstract = {Late-life depression is associated with greater disability, suicide risk and mortality than depression in mid-life, and is a risk factor/prodrome for neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Many depressed, older adults fail to respond to first line antidepressant treatment, experience relapse and exhibit persistent symptoms, including anxiety, apathy and cognitive impairment, that may reflect underlying neurodegenerative processes. Advances in molecular imaging, particularly positron emission tomography (PET) allow direct in-vivo investigation of neurobiological mechanisms underlying late-life depression symptom trajectories, treatment response and the potential links to neurodegenerative disease. Molecular imaging studies in late-life depression have revealed alterations across neurotransmitter systems and Alzheimer's disease pathology (beta-amyloid and Tau) and a potential role of neuroinflammation. In late-life depression, variability in symptom presentation and treatment response arises from interacting neurotransmitter, inflammatory, and neurodegenerative processes and potentially other molecular mechanisms that impair synaptic plasticity. Future directions include the application of next-generation PET tracers targeting glutamatergic signaling, mitochondrial function, histone deacetylase activity, and cell-type-specific inflammation, along with multi-modal image analysis methods to test mechanistic models . Molecular imaging holds significant promise for guiding the development of targeted, mechanism-based treatments that reduce the burden of late-life depression and its associated vulnerability to neurodegenerative disease.},
}