@article {pmid41735678,
year = {2026},
author = {Wang, J and Guo, Y and Han, W and Zhang, H and Jiang, P},
title = {D-serine: A Multitalented Neuromodulator in Brain Function, Systemic Homeostasis, and Disease.},
journal = {Cellular and molecular neurobiology},
volume = {46},
number = {1},
pages = {},
pmid = {41735678},
issn = {1573-6830},
support = {82501071//National Natural Science Foundation of China/ ; 82204032//National Natural Science Foundation of China/ ; 82202236//National Natural Science Foundation of China/ ; 82272253//National Natural Science Foundation of China/ ; ZR2023QH152//Natural Science Foundation of Shandong Province/ ; 2023YXNS037//the Key R&D Program of Jining/ ; 2023YXNS003//the Key R&D Program of Jining/ ; },
abstract = {UNLABELLED: D-serine is an endogenous D-amino acid and a crucial co-agonist for the N-methyl-D-aspartate (NMDA) receptor, well known as a key regulator of synaptic plasticity, learning, and memory. This review summarizes recent advances that extend beyond this canonical role, positioning D-serine as a dynamic nexus linking brain function to systemic homeostasis. We explore its spatiotemporal dynamics in synaptic microdomains, sophisticated epigenetic and transcriptional regulation, and emerging role as a metabolic sensor linking cellular energetics to neuronal signaling. Furthermore, we highlight novel non-canonical signaling pathways, including its function as a ligand for the glutamate delta-1 receptor (GluD1) and its direct role in peripheral organs like the gut and kidney. The pathophysiological implications of disrupted D-serine homeostasis are detailed across a spectrum of CNS disorders—from schizophrenia and Alzheimer’s disease (AD) to addiction and neuropathic pain—as well as in peripheral conditions including diabetic complications and osteoporosis. Finally, we discuss the translational potential of targeting D-serine pathways through innovative therapeutic strategies—such as serine racemase (SR) modulators, D-amino acid oxidase (DAAO) inhibitors, and gene therapy—and its promise as a biomarker for personalized medicine in neurology and psychiatry.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10571-026-01696-9.},
}

@article {pmid41844537,
year = {2026},
author = {Imms, P and Wang, H and Bhattacharya, S and Chaudhari, NN and Vega, OM and Solis Galvan, JA and Chen, S and Li, R and Irimia, A},
title = {Deep survival modelling to predict future cognitive impairment in unimpaired adults.},
journal = {The journals of gerontology. Series A, Biological sciences and medical sciences},
volume = {},
number = {},
pages = {},
doi = {10.1093/gerona/glag076},
pmid = {41844537},
issn = {1758-535X},
abstract = {BACKGROUND: Predicting Alzheimer's disease (AD)-related cognitive impairment (CI) among cognitively normal (CN) adults enables meaningful disease modification through early intervention and enrichment of clinical trials.

METHODS: A deep survival model is trained to predict CI conversion risk in 1,415 CN adults from the National Alzheimer's Coordinating Center. Converters' (N = 212) and non-converters' (N = 1,203) baseline clinical measures and magnetic resonance images are used to estimate their conversion probability up to 22 years after baseline observation.

RESULTS: After 20-fold cross-validation, the model predicts conversion probability with a c-index of 0.88, and classification accuracy of 75% and AUC ROC of 0.89, outperforming previous machine learning models.

CONCLUSIONS: This is one of few studies on the important challenge of predicting future CI among unimpaired subjects. Deep survival modelling can improve the identification of preclinical AD and suggests that uncertainty in AD risk estimation is due to potentially modifiable lifestyle factors.},
}

@article {pmid41844581,
year = {2026},
author = {Xie, Z and Liao, J and Xiong, J and Zhao, Z and Ye, K},
title = {C/EBPβ dictates postmenopausal FSHβ transcription and blockade of AEP/C/EBPβ pathway alleviates osteoporosis.},
journal = {Bone research},
volume = {14},
number = {1},
pages = {},
pmid = {41844581},
issn = {2095-4700},
support = {32330040//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82350710222//National Natural Science Foundation of China (National Science Foundation of China)/ ; KQTD2022110 1093608028//Shenzhen Science and Technology Innovation Commission/ ; JCYJ20220531100802005//Shenzhen Science and Technology Innovation Commission/ ; 82501723//National Science Foundation of China | Young Scientists Fund/ ; },
mesh = {Animals ; Female ; *CCAAT-Enhancer-Binding Protein-beta/metabolism/genetics ; Mice ; Humans ; *Follicle Stimulating Hormone, beta Subunit/genetics/metabolism ; *Transcription, Genetic ; Signal Transduction ; *Osteoporosis/genetics/metabolism ; *Osteoporosis, Postmenopausal/genetics/metabolism ; Ovariectomy ; Mice, Inbred C57BL ; *Postmenopause/metabolism/genetics ; Mice, Knockout ; },
abstract = {Follicle-stimulating hormone (FSH), a gonadotropin that rises in post-menopausal females, activates its receptor FSHR to trigger bone loss via increasing bone resorption by osteoclasts. FSH stimulates CCAAT/enhancer binding protein beta (C/EBPβ) /asparagine endopeptidase (AEP) pathway, facilitating neural degeneration in the brain of mouse models with Alzheimer's disease (AD). However, whether C/EBPβ/AEP pathway feeds back and modulates FSHβ bone resorption action remains elusive. Here we show that C/EBPβ acts as a transcription factor for fshb gene and directly binds its promoter, mediating its mRNA transcription in the pituitary gland. Knocking down C/EBPβ in primary pituitary cells significantly blunts GnRH (gonadotropin-releasing hormone)-induced FSHβ expression. Knockout of C/EBPβ also robustly diminishes FSHβ levels in mice. Inactivation of AEP, either by knockout of AEP or its small molecular inhibitor, antagonizes C/EBPβ and suppresses FSHβ levels, attenuating ovariectomy (OVX)-elicited osteoporosis. Markedly, a specific AEP inhibitor (#11a) displays comparable therapeutic effect as an FDA-approved drug teriparatide in OVX-induced osteoporosis. Hence, these findings support that C/EBPβ dictates FSHβ transcription and blocking AEP by its inhibitor represses C/EBPβ-mediated FSHβ levels, exerting prominent therapeutic efficacy toward osteoporosis.},
}

Animals
Female
*CCAAT-Enhancer-Binding Protein-beta/metabolism/genetics
Mice
Humans
*Follicle Stimulating Hormone, beta Subunit/genetics/metabolism
*Transcription, Genetic
Signal Transduction
*Osteoporosis/genetics/metabolism
*Osteoporosis, Postmenopausal/genetics/metabolism
Ovariectomy
Mice, Inbred C57BL
*Postmenopause/metabolism/genetics
Mice, Knockout

@article {pmid41844585,
year = {2026},
author = {Yang, M and Tong, L and Guo, Z and Tan, Z and Holmes, TC and Yu, Z and Xu, X},
title = {Evaluating the potential of acupuncture for Alzheimer's disease treatment: A meta-analysis and systematic review of mouse model studies.},
journal = {Translational psychiatry},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41398-026-03923-9},
pmid = {41844585},
issn = {2158-3188},
abstract = {Acupuncture is an ancient practice that was developed within the framework of traditional Chinese medicine. While acupuncture has been recently proposed as a therapy for Alzheimer's disease (AD), acupuncture effects are not well understood in terms of neural mechanisms. Here, we review and examine the studies that used AD mouse models and analyze the experiments where researchers administered electroacupuncture (EA) to AD mice to assess the potential therapeutic impact of acupuncture on disease pathology and cognitive function in controlled laboratory settings. We analyzed 29 relevant PubMed articles published between January 2014 and July 2025. Our results reveal that EA significantly reduces both amyloid-beta (Aβ) and phosphorylated tau (p-tau) levels and neuroinflammatory biomarkers, including molecular signatures for activated microglia and astrocytes in the brain. EA also enhances cognitive functions. While no study directly compared acupoint strategies, the indirect comparisons in our network analysis suggest that GV20 has potential as a therapeutic target for AD. Our present meta-analysis and review of literature add to the evidence of integrative health practices for acupuncture-based Alzheimer's disease treatment.},
}

@article {pmid41844597,
year = {2026},
author = {Badia, M and Batlle, C and Bolognesi, B},
title = {Massively parallel quantification of mutational impact on IAPP amyloid formation.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-70611-z},
pmid = {41844597},
issn = {2041-1723},
support = {101125484//European Commission (EC)/ ; PID2021-127761OB-I00//Ministry of Economy and Competitiveness | Agencia Estatal de Investigación (Spanish Agencia Estatal de Investigación)/ ; RYC2020-028861-I//Ministry of Economy and Competitiveness | Agencia Estatal de Investigación (Spanish Agencia Estatal de Investigación)/ ; PRE2019-088300//Ministry of Economy and Competitiveness | Agencia Estatal de Investigación (Spanish Agencia Estatal de Investigación)/ ; LCF/PR/HR21/52410004//"la Caixa" Foundation (Caixa Foundation)/ ; },
abstract = {Amyloid fibrils formed by the islet amyloid polypeptide cause pancreatic beta-cell damage, resulting in reduced insulin secretion and type 2 diabetes. Changes in the amino acid sequence of this peptide can influence its aggregation rate, and animals expressing variants that do not form amyloids do not develop type 2 diabetes. Conversely, specific single amino acid changes can accelerate the aggregation rate of this peptide. Here, we employ deep mutational scanning to measure the ability of 1916 islet amyloid polypeptide variants, including substitutions, insertions, truncations and deletions, to nucleate amyloids. Our results identify a continuous stretch of residues from 15 to 32 that is particularly sensitive to mutation. This region, which is likely structured in amyloids, matches the core of the early aggregated species formed by this peptide in vitro. Within this region, mutations in residues 21 to 27 have a substantial effect, suggesting tighter structural constraints. Finally, we compare the mutational atlas of the islet amyloid polypeptide to that of amyloid beta - the peptide that aggregates in Alzheimer's disease - and find that mutations that slow down nucleation correlate between the two amyloids, but mutations that accelerate nucleation in one amyloid cannot be used to predict mutational effects in the other.},
}

@article {pmid41844663,
year = {2026},
author = {Rusko, M and Brandoburová, P and Kevická, V and Trnka, M and Sabo, R and Darjaa, S and Malschitz, R},
title = {Database of Speech and Language Affected by Mild Cognitive Impairment.},
journal = {Scientific data},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41597-026-07071-z},
pmid = {41844663},
issn = {2052-4463},
support = {APVV-21-0373//Agentúra na Podporu Výskumu a Vývoja/ ; APVV-21-0373//Agentúra na Podporu Výskumu a Vývoja/ ; APVV-21-0373//Agentúra na Podporu Výskumu a Vývoja/ ; APVV-21-0373//Agentúra na Podporu Výskumu a Vývoja/ ; APVV-21-0373//Agentúra na Podporu Výskumu a Vývoja/ ; APVV-21-0373//Agentúra na Podporu Výskumu a Vývoja/ ; APVV-21-0373//Agentúra na Podporu Výskumu a Vývoja/ ; 2/0092/25//Vedecká Grantová Agentúra MŠVVaŠ SR a SAV/ ; 2/0092/25//Vedecká Grantová Agentúra MŠVVaŠ SR a SAV/ ; 2/0092/25//Vedecká Grantová Agentúra MŠVVaŠ SR a SAV/ ; 09I05-03-V02-00055//EU Recovery Program/ ; 09I05-03-V02-00055//EU Recovery Program/ ; 09I05-03-V02-00055//EU Recovery Program/ ; },
abstract = {Mild Cognitive Impairment (MCI) is increasingly recognized as an early indicator of neurodegenerative diseases, including Alzheimer's disease (AD). Speech and language deficits are known to emerge already in the MCI stage of various aetiologies. The ALOIS database (ALOIS-DB) was created to support research and development in this area by creating and providing a corpus of speech from Slovak-speaking individuals diagnosed with MCI and cognitively healthy controls. The dataset includes recordings from 258 participants (102 MCI, 156 controls), collected through a battery of nine speech and language tasks targeting various speech and language domains. All recordings were obtained using a custom-developed tablet application and were transcribed and annotated according to established protocols. The resulting dataset is accompanied by metadata and is publicly available for research purposes. ALOIS-DB represents a valuable resource for developing automated tools for the detection of early cognitive decline and contributes to the growing body of speech data relevant to neurocognitive disorders.},
}

@article {pmid41844810,
year = {2026},
author = {Ullah, W and Dai, Q and Zulqarnain, RM and Fiidow, MA},
title = {Explainable artificial intelligence for early Alzheimer's diagnosis using enhanced grey relational features and multimodal data.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-43707-1},
pmid = {41844810},
issn = {2045-2322},
support = {62476126//National Natural Science Foundation of China/ ; },
abstract = {Alzheimer's disease, a progressive neurodegenerative disorder, presents a growing global health challenge due to its increasing prevalence and lack of accessible early diagnostic methods. Even though it has enhanced the diagnostic accuracy of machine learning, there is a major concern about striking a balance between predictive performance and interpretability. The proposed study presents an interpretable and sustainable machine learning architecture for early diagnosis of Alzheimer's disease based on multimodal, structured clinical and behavioral data, including demographics, vascular risk factors, lifestyle, and cognitive data. We perform extensive feature engineering to derive composite features, including blood pressure ratio, MMSE age ratio, cholesterol ratio, and cognitive decline score. The class imbalance is addressed using the Synthetic Minority Oversampling Technique. We also introduce a new strengthened Grey Relational Grade index based on the theory of grey system and the policy of sigmoid normalization. This greatly enhances the feature-diagnosis correlation (0.725 to 0.891), representing complicated nonlinear associations. This paper compared seven mainstream classifiers, such as Logistic Regression, Random Forest, Extreme Gradient Boosting, Light Gradient Boosting Machine, CatBoost, Stacking Ensembles, and Deep Neural Networks, in the context of model comparison. Among them, Deep Neural Networks achieve the best performance (accuracy: 98.01%, AUC: 99.43%), followed by a CatBoost-based Stacking Ensemble (Accuracy: 97.91%, AUC: 98.10%). Shapley Additive Explanations make models easier to understand by showing important modifiable predictors like family history, smoking, and early cognitive symptoms. This study presents that combining enhanced Grey Relational Grade metrics with robust machine learning and deep learning models produces an accurate, interpretable, and potentially effective framework for early AD risk assessment, which can be used to implement effective, behavior-centric prevention strategies in ageing demographics.},
}

@article {pmid41845424,
year = {2026},
author = {Valera-Barrero, A and Martínez-Dubarbie, F and Guerra, A and López-García, S and Lage, C and Rivera-Sánchez, M and Pozueta-Cantudo, A and García-Martínez, M and Corrales-Pardo, A and Bravo, M and López-Hoyos, M and Irure-Ventura, J and Cahuana-Santamaría, H and García-Unzueta, MT and Di Molfetta, G and Blennow, K and Ashton, NJ and Zetterberg, H and Sánchez-Juan, P and Rodríguez-Rodríguez, E and Fernández-Matarrubia, M},
title = {Diagnostic performance of plasma GFAP in preclinical stages of Alzheimer's disease using the Lumipulse platform.},
journal = {Alzheimer's research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13195-026-02012-9},
pmid = {41845424},
issn = {1758-9193},
}

@article {pmid41845487,
year = {2026},
author = {Wu, J and Ge, Y and Zhang, L and Huang, J and Huang, N and Luo, Y},
title = {Tanshinone IIA-pretreated mesenchymal stem cells alleviate neuroinflammation in 3×Tg-AD mice via the TREM2/PI3K/Akt pathway.},
journal = {Stem cell research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13287-026-04954-1},
pmid = {41845487},
issn = {1757-6512},
support = {ZK [2024]-680//Science and Technology Department of Guizhou Province/ ; ZK [2021]-570//Science and Technology Department of Guizhou Province/ ; 82160858//National Natural Science Foundation of China/ ; HZ-2022-45, [2024] No. 6, HZ-2025-06//Zunyi Science and Technology Bureau/ ; ZSYS(2025)040//Guizhou Provincial Science and Technology Department/ ; },
abstract = {Neuroinflammation is a key pathogenic factor for neurodegenerative diseases. Mesenchymal stem cell (MSC) transplantation, as a potential strategy for regulating neuroinflammation, has received extensive attention. Our previous research revealed that compared with ordinary MSC, MSC pretreated with tanshinone IIA (TIIA), referred to as TIIA-MSC, exhibited superior anti-neuroinflammatory activity, but the mechanism of action remains unclear. To clarify the underlying mechanism, this study integrated in vitro and in vivo experiments and evaluated the therapeutic effect of TIIA-MSC in a triple-transgenic Alzheimer's disease mouse model (3×Tg-AD mice) and explored its mechanism of action in a lipopolysaccharide (LPS)-induced BV2 microglial cell inflammation model. The results showed that TIIA-MSC could significantly improve the cognitive function of 3×Tg-AD mice, increase brain glucose metabolism levels, promote the recovery of synaptic and mitochondrial structures, and effectively alleviate neuroinflammatory responses. In vitro experiments further verified the superior inhibitory effect of TIIA-MSC on microglial cell activation and proinflammatory factor release. Mechanistic studies have indicated that the triggering receptor expressed on myeloid cells 2 (TREM2) is the key molecule that mediates this process. The knockdown of TREM2 expression significantly weakened the anti-inflammatory effect of TIIA-MSC, suggesting that TREM2 plays a central role in this process. Further analysis revealed that by activating the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway downstream of TREM2, TIIA-MSC may promote the transformation of the functional state of microglia from mainly proinflammatory to having neuroprotective and repair properties. This study systematically revealed the molecular mechanism by which TIIA-MSC regulate microglial cell phenotypic transformation through the TREM2/PI3K/Akt pathway and exert anti-neuroinflammatory effects, providing new ideas and an experimental basis for expanding the application of MSC in the treatment of neurodegenerative diseases.},
}

@article {pmid41845493,
year = {2026},
author = {van der Schaar, J and Visser, LNC and Asscher, ECA and Pijnenburg, YAL and de Geus, CM and van der Flier, WM and Bredenoord, AL and van den Hoven, MA and Smets, EMA and van der Lee, SJ},
title = {Impact of diagnostic genetic testing for familial dementia: experiences of patients and relatives.},
journal = {Alzheimer's research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13195-026-02000-z},
pmid = {41845493},
issn = {1758-9193},
support = {73305095007/ZONMW_/ZonMw/Netherlands ; 73305095007/ZONMW_/ZonMw/Netherlands ; 73305095007/ZONMW_/ZonMw/Netherlands ; 73305095007/ZONMW_/ZonMw/Netherlands ; 73305095007/ZONMW_/ZonMw/Netherlands ; LSHM20106//Health∼Holland, Topsector Life Sciences & Health/ ; LSHM20106//Health∼Holland, Topsector Life Sciences & Health/ ; LSHM20106//Health∼Holland, Topsector Life Sciences & Health/ ; LSHM20106//Health∼Holland, Topsector Life Sciences & Health/ ; LSHM20106//Health∼Holland, Topsector Life Sciences & Health/ ; 733050512//Nederlandse Organisatie voor Wetenschappelijk Onderzoek/ ; },
}

@article {pmid41845577,
year = {2026},
author = {Zhao, J and Huang, R and Bu, N and Wang, H and Zhang, S and Pan, Y and Su, Y and Wei, Z and Chen, Y and Li, Y and Dong, X and Li, Y and Wei, J and Zhao, X and Lin, L and Sun, K},
title = {Advances in the Use of Traditional Chinese Medicine Prescriptions for Alzheimer's Disease.},
journal = {Psychogeriatrics : the official journal of the Japanese Psychogeriatric Society},
volume = {26},
number = {3},
pages = {e70157},
doi = {10.1111/psyg.70157},
pmid = {41845577},
issn = {1479-8301},
support = {NGBJ-2020-30//The Doctoral Scientific Research Foundation for Returned Scholars from Nanyang Institute of Technology/ ; YJS2025GZZ58//Postgraduate Education Reform and Quality Improvement Project of Henan Province/ ; 242102111123//Henan Provincial Science and Technology Research Project/ ; 222102310357//Science and Technology Research Project of Henan Provincial/ ; },
mesh = {*Alzheimer Disease/drug therapy/therapy ; Humans ; *Medicine, Chinese Traditional/methods ; *Drugs, Chinese Herbal/therapeutic use ; Gastrointestinal Microbiome ; },
abstract = {Alzheimer's disease (AD) is a neurodegenerative disease characterised by progressive cognitive and memory impairment. Recent research on neurodegenerative diseases has demonstrated the importance of the brain-gut axis, which has gradually become a hotspot in the field of AD research. The gut microbiota has been shown to be involved in the pathogenesis and treatment of neurodegenerative diseases such as AD. Traditional Chinese medicine (TCM) has been used for millennia in China for the treatment of disease. This article summarises recent research on the use of TCM prescriptions for treating AD. It is hoped that this review will provide new ideas for the treatment of AD.},
}

*Alzheimer Disease/drug therapy/therapy
Humans
*Medicine, Chinese Traditional/methods
*Drugs, Chinese Herbal/therapeutic use
Gastrointestinal Microbiome

@article {pmid41845865,
year = {2026},
author = {Hu, Z and Raji, MA and Shan, Y and Tzeng, HM and O'Mahony, S and Kuo, YF},
title = {Annual Wellness Visits and Timing of Advance Care Planning Among Medicare Beneficiaries With Cognitive Impairment.},
journal = {Journal of the American Geriatrics Society},
volume = {},
number = {},
pages = {},
doi = {10.1111/jgs.70368},
pmid = {41845865},
issn = {1532-5415},
support = {R01AG083102/AG/NIA NIH HHS/United States ; },
abstract = {BACKGROUND: Advance care planning (ACP) allows older adults to document preferences for future medical care, but uptake remains limited and unequal, especially among those with mild cognitive impairment (MCI) or Alzheimer's disease and related dementias (ADRD). Since 2016, ACP discussions can be billed during the Medicare annual wellness visit (AWV), creating a policy-supported opportunity for timely ACP engagement.

PARTICIPANTS AND SETTING: We studied 959,405 Medicare beneficiaries aged ≥ 68 years newly diagnosed with MCI or ADRD in 2018, using national claims data.

METHODS: We conducted a retrospective cohort study with 1:1 propensity score matching to compare beneficiaries with and without AWV receipt in 2018. Cox proportional hazards models with death as a competing risk estimated associations between AWV and ACP initiation over 4 years. Sensitivity analyses included censoring rules and time-dependent modeling. Subgroup analyses assessed variation by cognitive stage, race/ethnicity, sex, region, and education.

RESULTS: Among 118,174 beneficiaries who received an AWV, 27.62% initiated ACP within 4 years compared with 17.46% of nonrecipients (HR, 1.86; 95% CI, 1.84-1.89). Most ACP uptake among AWV recipients occurred on the same day as the visit (9.00%), with modest increases thereafter. Sensitivity analyses confirmed stronger associations when accounting for continued AWV use (HR, 2.51; 95% CI, 2.46-2.56) and with time-dependent modeling (HR, 2.27; 95% CI, 2.27-2.31). The positive association between AWV and ACP was consistent across subgroups and particularly strong among Hispanic beneficiaries and those in nonmetropolitan areas.

CONCLUSIONS: AWV receipt was associated with significantly earlier and greater ACP initiation among older adults with MCI or ADRD. Incorporating ACP into AWV workflows could enhance timely engagement, reduce disparities, and strengthen alignment of care with patient preferences. System-level interventions and clinician training may further increase same-day ACP uptake.},
}

@article {pmid41845988,
year = {2026},
author = {Zhu, X and Lai, X and Deng, J and Long, Y},
title = {Naturally occurring antibodies against ASC reduced in Alzheimer's disease and alleviating AD-type pathology in APP/PS1 mouse.},
journal = {Experimental neurology},
volume = {},
number = {},
pages = {115728},
doi = {10.1016/j.expneurol.2026.115728},
pmid = {41845988},
issn = {1090-2430},
abstract = {The disruption or increased permeability of the blood-brain barrier (BBB) results in dysregulated autoantibody profiles in Alzheimer's disease (AD) patients. Naturally occurring antibodies against ASC (NAbs-ASC), which are present in human blood, can block the ability of ASC specks to seed Aβ aggregation. However, the characteristics and functions of NAbs-ASC in AD remain unclear. In this study, we found that plasma levels of NAbs-ASC were reduced in AD patients and showed a negative correlation with the severity of cognitive impairment and with plasma Aβ42/40 ratios. NAbs-ASC treatment reduced Aβ production and attenuated Aβ-induced cytotoxicity in AD cell models. Furthermore, passive immunization with NAbs-ASC or active immunization with ASC peptides improved cognitive function, attenuated Aβ deposition, reduced Tau phosphorylation, inhibited neuroinflammation and apoptosis, and improved synaptic plasticity in APP/PS1 mice. These findings support that NAbs-ASC may be an important physiological protective factor for AD, and that Immunotherapy targeting ASC may be a potential therapeutic intervention for the disease.},
}

@article {pmid41845989,
year = {2026},
author = {Zhao, Y and Chen, W and Zhou, F},
title = {IL-1β neutralization ameliorates cognitive deficits and tau pathology in a mouse model of Alzheimer's disease with Hyperhomocysteinemia.},
journal = {Experimental neurology},
volume = {},
number = {},
pages = {115729},
doi = {10.1016/j.expneurol.2026.115729},
pmid = {41845989},
issn = {1090-2430},
abstract = {BACKGROUND: Hyperhomocysteinemia (HHcy) is an important risk factor for Alzheimer's disease (AD), but its differential effects on tau pathology and beta-amyloid (Aβ) deposition, as well as the key mediating molecules involved, remain unclear. This study investigates how HHcy influences AD pathology and examines whether interleukin-1β (IL-1β) neutralization can mitigate HHcy-accelerated neurodegeneration.

METHODS: Female 12-month-old 3 × Tg-AD mice were supplemented with methionine water for 7 weeks to induce HHcy. Brain tissues were analyzed for Aβ deposition, tau phosphorylation, oligomerization, and neurofibrillary tangle formation using ELISA, immunohistochemistry, Western blot, and Thioflavin S staining. To assess the role of IL-1β, HHcy-AD mice were treated with an anti-IL-1β monoclonal antibody (mAb; 100 μg, twice weekly for two weeks). Moreover, behavioral performance was evaluated using the Morris water maze for the effect of IL-1β neutralization.

RESULTS: HHcy significantly exacerbated tau pathology, increasing oligomeric tau levels, hyperphosphorylation (AT-8, Ser396, Thr231), and neurofibrillary tangles, particularly in the cortex. In contrast, HHcy had minimal effects on Aβ deposition, only increasing insoluble Aβ1-40. Anti-IL-1β mAb treatment reduced tau phosphorylation and oligomerization, coinciding with inactivation of hippocampal GSK3β (increased p-Ser9). The mAb also improved cognitive function but showed selective effects on Aβ pathology and differentially modulated glial responses across brain regions.

CONCLUSION: HHcy preferentially exacerbates tauopathy rather than amyloidosis in 3 × Tg-AD mice. IL-1β neutralization ameliorates tau-related pathology and cognitive deficits, likely through regional suppression of GSK3β activity, highlighting its potential as a therapeutic strategy for tau-focused AD interventions.},
}

@article {pmid41846133,
year = {2026},
author = {Zhao, H and Xie, J and Wu, S and Zhao, X and Yu, S and Freeman, JL and Rochet, JC and Yuan, C},
title = {Comparative neurotoxic effects of PFOA and GenX in hiPSC-derived cortical neurons.},
journal = {Journal of hazardous materials},
volume = {507},
number = {},
pages = {141766},
doi = {10.1016/j.jhazmat.2026.141766},
pmid = {41846133},
issn = {1873-3336},
abstract = {Per- and polyfluoroalkyl substances (PFAS) are widely used in daily consumer and industrial products, and human exposure to PFAS has been associated with various neuronal disorders, including Alzheimer's disease (AD), although the underlying mechanisms remain poorly understood. In this study, we investigated the neurotoxic effects of PFOA, a legacy PFAS, and GenX, its proposed "safer" alternative, using human induced pluripotent stem cell (hiPSC)-derived cortical neurons. To assess persistent neurotoxicity, neurons were assessed immediately after exposure and after a 7-day recovery. Neuronal resilience was evaluated using a secondary challenge assay targeting organelle-specific stressors. We identified distinct neurotoxic effects of PFOA and GenX, leading to increased risk of developing AD. PFOA exposure induced transient alteration in neuronal activity, neuron network morphology and synaptic density, but with persistent damage in mitochondria function, further corroborated with increased vulnerability towards mitochondria stress. GenX exposed neurons showed persistent alteration in neuronal network morphology and synaptic density, accompanied by persistent increase in vulnerability towards autolysosomal stress. Both PFOA and GenX triggered transient changes in AT8 and tau expression and conferred persistent vulnerability to tau-preformed fibrils (tau-PFF), implicating impaired proteostasis. Transcriptomic profiling further supported our findings. Collectively, our findings reveal divergent neurotoxic mechanisms of PFOA and GenX-mitochondrial damage versus autolysosomal stress-that converge on tau pathology, highlighting increased AD risk induced by PFAS exposure.},
}

@article {pmid41846151,
year = {2026},
author = {Huang, J and Rehman, H and Doan, C and Stein, TD and Mez, J and Ang, TFA and Tao, Q and Au, R and Farrer, LA and Zhang, X and Qiu, WQ},
title = {Corrigendum to 'Circulating C-reactive protein influences polygenic risk of inflammatory genes expressed in brain endothelia for Alzheimer's disease' Neurobiology of Disease 219 (2026) Article Number 107257.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107348},
doi = {10.1016/j.nbd.2026.107348},
pmid = {41846151},
issn = {1095-953X},
}

@article {pmid41846157,
year = {2026},
author = {Rajkumar, G and Uthayakumar, H and Khoury, MA and Valcic, M and Rashidi-Ranjbar, N and Churchill, NW and Fornazzari, LR and De Luca, V and Ismail, Z and Graham, SJ and Munoz, DG and Schweizer, TA and Fischer, CE},
title = {Genetic and Hormonal Contributions to Psychosis Symptoms in Alzheimer's Disease: A Sex-Stratified Analysis.},
journal = {The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jagp.2026.02.011},
pmid = {41846157},
issn = {1545-7214},
abstract = {OBJECTIVE: Psychosis in Alzheimer's disease (AD), including hallucinations and delusions, affects up to 50% of patients and is linked to faster cognitive decline. Delusions can occur across AD, with persecutory delusions early and misidentification delusions late, while hallucinations emerge in advanced stages and predict greater cognitive and functional decline. The APOE4 allele is the strongest genetic risk factor for late-onset AD, although its influence on neuropsychiatric symptoms, including psychosis, remains unclear. This study examined the interaction between APOE4 status, sex, EHT use, and psychosis symptoms in AD using data from participants in the National Alzheimer's Coordinating Center Uniform Data Set.

METHODS: Generalized Additive Models assessed nonlinear associations between predictors and psychosis outcomes, including the presence of delusions, hallucinations, and their visual and auditory subtypes. Analyses were stratified by sex (males: n = 13,841, females: n = 15,354). Predictor variables included APOE4 status, current use of estrogen hormone therapy (EHT) in females. Due to limited data availability, CSF biomarkers (Aβ1-42, p-tau181, t-tau) could not be included in the main models and were instead examined in a secondary sub analysis.

RESULTS: APOE4 homozygosity was associated with significantly greater odds of delusions in the past month in both males and females, with a stronger effect in females (p<0.05). In females only, APOE4 homozygosity was significantly associated with hallucinations, with no effect in males (p<0.05). EHT was associated with lower risk of hallucinations in females (p<0.05).

CONCLUSIONS: These findings underscore sex-specific genetic and biological contributors to psychosis in AD and support sex-stratified approaches to understanding and addressing psychosis symptoms in clinical settings.},
}

@article {pmid41846418,
year = {2026},
author = {Ahire, C and Yadav, R and Bhamare, UU and Kaur, G and Palkar, MB},
title = {From Refractory Epilepsy to Neurodegeneration: Emerging Mechanistic and Clinical Insights Into the Ketogenic Diet.},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
volume = {40},
number = {6},
pages = {e71609},
doi = {10.1096/fj.202503317R},
pmid = {41846418},
issn = {1530-6860},
mesh = {*Diet, Ketogenic/methods ; Humans ; Animals ; *Neurodegenerative Diseases/diet therapy/metabolism ; *Drug Resistant Epilepsy/diet therapy/metabolism ; },
abstract = {The ketogenic diet (KD), a high-fat, low-carbohydrate intervention, is well established for drug-resistant epilepsy and is increasingly explored in neurodegenerative disorders. KD reduces neuronal hyperexcitability through enhanced γ-aminobutyric acid (GABA)ergic transmission and modulation of neurotransmitter balance, underlying its efficacy in refractory epilepsy. Beyond seizure control, emerging evidence suggests KD may influence disease processes in conditions such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, and Huntington's disease. Preclinical studies indicate that KD can modulate mitochondrial bioenergetics, oxidative stress, neuroinflammation, neurotransmitter signaling, and gut-brain interactions, though these effects are highly context-dependent and primarily derived from cellular and animal models. Clinical data remain limited, heterogeneous, and short-term, with small cohorts and variable outcome measures. Sustaining adherence and assessing long-term safety remain significant challenges in patient populations. This review summarizes recent experimental and clinical findings, highlighting the molecular and cellular mechanisms through which KD exerts neuroprotective effects. We also evaluate translational evidence and discuss the potential utility of KD as an adjunctive intervention in neurological disease management.},
}

*Diet, Ketogenic/methods
Humans
Animals
*Neurodegenerative Diseases/diet therapy/metabolism
*Drug Resistant Epilepsy/diet therapy/metabolism

@article {pmid41846469,
year = {2026},
author = {Fan, W and Cheng, J and Tian, Q and Wu, R and Zou, J and Si, W and Chen, Z and Wang, S},
title = {Tensor-decomposition regularized learning for fast and high-fidelity multi-parametric microstructural MR imaging.},
journal = {Medical physics},
volume = {53},
number = {3},
pages = {e70359},
doi = {10.1002/mp.70359},
pmid = {41846469},
issn = {2473-4209},
support = {U22A2040//National Natural Science Foundation of China/ ; B2402047//Shenzhen Medical Research Fund/ ; QNXMA20250701100018023//Shenzhen Science and Technology Program/ ; 2023B1212060052//Key Laboratory for Magnetic Resonance and Multimodality Imaging of Guangdong Province/ ; //Youth Innovation Promotion Association of the Chinese Academy of Sciences/ ; },
mesh = {*Deep Learning ; Humans ; *Image Processing, Computer-Assisted/methods ; *Magnetic Resonance Imaging/methods ; Brain/diagnostic imaging ; Time Factors ; Alzheimer Disease/diagnostic imaging ; Diffusion Magnetic Resonance Imaging ; Connectome ; },
abstract = {BACKGROUND: Deep learning (DL) has emerged as a promising approach for learning the nonlinear mapping between diffusion-weighted MR images and tissue parameters, enabling automatic and in-depth understanding of brain microstructures. However, the efficiency and accuracy of jointly estimating multiple microstructural parameters derived from various diffusion models remain limited due to isolated signal modeling and dense sampling requirements.

PURPOSE: This study aims to develop a unified DL framework for fast and high-fidelity estimation of multiple microstructural parameters derived from different diffusion models using sparsely sampled q-space data.

METHODS: We propose DeepMpMRI, an efficient and extendable framework equipped with a novel tensor-decomposition-based regularizer that captures fine structural details by exploiting high-dimensional correlations across parameters. In addition, a Nesterov-based adaptive learning algorithm is introduced to dynamically optimize the regularization parameter, improving both efficiency and reconstruction accuracy.

RESULTS: Experimental results on the Human Connectome Project (HCP) dataset and an Alzheimer's disease dataset demonstrate that DeepMpMRI outperforms five state-of-the-art methods in simultaneously estimating DKI- and NODDI-derived parameter maps, achieving 4.5-15 × $\times$ acceleration compared to dense sampling with 270 diffusion gradients.

CONCLUSIONS: DeepMpMRI enables accurate and robust multi-parametric microstructural imaging under sparse sampling conditions, showing strong potential for clinical translation in efficient diffusion MRI-based tissue characterization.},
}

*Deep Learning
Humans
*Image Processing, Computer-Assisted/methods
*Magnetic Resonance Imaging/methods
Brain/diagnostic imaging
Time Factors
Alzheimer Disease/diagnostic imaging
Diffusion Magnetic Resonance Imaging
Connectome

@article {pmid41846945,
year = {2026},
author = {Schweitzer, N and Shen, Y and Zhao, Y and Cover, C and Alam, S and Deek, R and Li, J and Stetten, G and Aizenstein, H and Wu, M and Koldamova, R and Vazquez, A and Fitz, NF and Iordanova, B},
title = {Linking cross-species trajectories of cerebrovascular remodeling in aging and Alzheimer's disease to brain vessel transcriptome.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.03.06.710077},
pmid = {41846945},
issn = {2692-8205},
abstract = {Cerebrovascular remodeling driven by subtle molecular changes starts early in the asymptomatic stage of Alzheimer's disease (AD). Despite progress in human vascular imaging and postmortem tissue analysis, there is limited data on the early features of small vessel reorganization, particularly in the context of cell-specific molecular drivers. This is largely because of the invasive nature of the tools for direct cellular observation and analysis. Since early detection is key, histopathology falls short with end-point data from people that died in late stages of the disease. This is a critical knowledge gap, because the early vascular processes are thought to be strongly correlated with health outcomes, tipping the scales from mild cognitive impairment to AD. To meet these translational challenges, we performed near life-span in vivo two-photon imaging and MRI of the cerebrovascular tree in a mouse model of amyloidosis. We identified precisely when subtle abnormalities in vessel tortuosity and red blood cell velocity first emerge in the context of differential amyloid accumulation in vessels walls and tissues. We then isolated the brain vessels for transcriptional analysis at this flagship timepoint and performed cross-species analysis linking changes in vascular cells to genes and pathways common to both mice and humans. Importantly, using 7T MRI of aging humans, we directly associated vascular remodeling trajectories of mice and humans and identified a remarkably analogous tortuosity course in the smallest brain vessels. Our integrated framework across scales and species advances neuroimaging biomarker understanding and uncovers early mechanistic routs of dysfunctional angiogenesis and actin-mediated contractility.},
}

@article {pmid41847004,
year = {2026},
author = {McCool, S and Smith, JC and Van Hook, MJ},
title = {Plaque-associated Microglial Polarization in Visual Brain Regions of the 5xFAD Mouse Model.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.02.27.708522},
pmid = {41847004},
issn = {2692-8205},
abstract = {Alzheimer's disease (AD), a neurodegenerative disorder associated with amyloid beta (Aβ) plaque deposition, leads to cognitive decline in affected individuals. Vision changes are some of the first reported symptoms in AD with studies showing both decline in functions performed by the visual system as well as associations between vision loss and cognitive impairment in AD patients. Due to the increasing number of individuals diagnosed with AD and its early impact on vision, we sought to provide an in-depth analysis using immunohistochemistry and 2-photon imaging techniques in the 5xFAD mouse model of amyloidosis to examine specifically how Aβ, a primary pathology typically preceding many other AD-associated pathologies, affects visual regions of the brain and how microglia, key immune regulators of the brain's environment, respond to this AD-like pathology. We found that in the pathway for image-forming vision, including the dorsolateral geniculate nucleus (dLGN) and the primary visual cortex (V1), there was significant Aβ pathology and shifts in microglial morphology to an amoeboid state and increased phagocytic activity. However, in non-image-forming visual brain regions such as the superior colliculus (SC) and suprachiasmatic nucleus (SCN), there was minimal Aβ pathology, ramified microglial morphology, and minimal phagocytic activity. Overall, visual brain regions associated with Aβ plaque deposition experience significant microglial polarization when examining both morphology and function.},
}

@article {pmid41847148,
year = {2026},
author = {Yuan, X and Tang, Q and Wang, T},
title = {Nanotechnology-based targeted delivery strategies for the treatment of Alzheimer's disease.},
journal = {Nanoscale advances},
volume = {},
number = {},
pages = {},
pmid = {41847148},
issn = {2516-0230},
abstract = {Alzheimer's disease (AD), as a common neurodegenerative disorder, seriously affects human health. However, the treatment of AD has always faced significant challenges and has attracted extensive attention in medical research. In recent years, nanoparticle-based therapeutic strategies have been identified as a promising direction in AD research due to their unique advantages and potential. These strategies leverage the distinctive physical and chemical properties of nanomaterials, enabling them to effectively traverse the blood-brain barrier and directly target pathological sites, thereby minimizing damage to normal tissues and enhancing therapeutic efficacy. This approach holds considerable promise for AD treatment. Current literature indicates that nanomedicines can deliver therapeutic agents, such as approved pharmaceuticals, natural compounds, antibodies, and metal nanoparticles, directly to lesion sites, thereby reducing collateral damage to healthy tissues and improving treatment outcomes. With continuous advancements in nanotechnology and ongoing scientific investigations, there is potential for developing safer and more effective treatment options for AD patients in the future. This review aims to summarize recent developments in nanoparticle-based strategies for AD therapy and elucidate their mechanisms of action, providing new insights for the future development and advancement of nanomedicines in this domain.},
}

@article {pmid41847265,
year = {2025},
author = {Agtas, G and Singh, K and Park, H and Mukerji, S},
title = {Plasma Biomarkers and Cognitive Decline in HIV: Findings from Two U.S. Cohorts.},
journal = {TouchREVIEWS in infectious diseases},
volume = {4},
number = {1},
pages = {22-27},
pmid = {41847265},
issn = {2755-113X},
abstract = {With advances in antiretroviral treatment, the population of older people living with HIV (PLWH) is increasing rapidly, leading to a rise in cognitive impairment related to both HIV and aging. Plasma biomarkers have been extensively investigated as non-invasive tools to help detect neurodegeneration in PLWH. This review compares cross-sectional and longitudinal findings from two recent substudies conducted within U.S. cohorts, the AIDS Clinical Trials Group HAILO study and the Women's Interagency HIV Study (WIHS), both of which investigated the relationship between plasma biomarkers and cognitive performance in PLWH. This review focuses on the common biomarkers evaluated in both studies: neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP). Both studies demonstrated longitudinal associations between elevated NfL levels and poor cognitive performance, particularly in processing speed. In contrast, GFAP showed inconsistent associations, suggesting its utility will be limited in clinical settings. Given that effect sizes across both studies ranged from small to modest, further validation in diverse aging cohorts with domain specific cognitive assessments is needed before routine clinical use.},
}

@article {pmid41847401,
year = {2026},
author = {Papacocea, RI and Ciobanu, AM},
title = {A taxon-centered review of bacterial shifts in psychiatric disorders.},
journal = {Frontiers in psychiatry},
volume = {17},
number = {},
pages = {1702172},
pmid = {41847401},
issn = {1664-0640},
abstract = {BACKGROUND: Psychiatric conditions rank among the leading causes of disability worldwide, with their burden steadily increasing in recent years. Recent research highlights the gut-brain axis as a pivotal pathway in mental health, implicating gut microbiota shifts in conditions such as depression, anxiety, schizophrenia, bipolar disorder, autism spectrum disorder, Alzheimer's disease and others. However, most reviews remain diagnosis-centered.

METHODS: We conducted a structured literature review of articles published between January 2015 and July 2025 in PubMed, Scopus, and Web of Science. We included both human and animal studies that reported taxonomic changes in gut microbiota associated with psychiatric or neurodevelopmental disorders. Editorials, conference abstracts, and studies lacking full-text availability, not addressing psychiatric outcomes or specific taxonomic data were excluded. Thus, data on bacterial taxa reported as increased or decreased versus controls were extracted and reorganized into a taxon-centered database.

RESULTS: The analysis suggested distinct yet overlapping microbial alterations across psychiatric conditions. Taxa such as Coprococcus and Faecalibacterium were repeatedly reported as decreased in multiple disorders, suggesting a possible reduction in taxa commonly associated with anti-inflammatory functions, while Bacteroides, Lactobacillus, and Clostridium were reported in context-dependent associations. Some genera (e.g., Desulfovibrio, Klebsiella, Methanobrevibacter) were reported as enriched across disorders, potentially reflecting shared inflammatory-related profiles. This transdiagnostic mapping highlights microbial taxa that recur across psychiatric conditions and may represent candidates for further investigation.

CONCLUSION: By changing the perspective from diagnosis to taxon-centered analysis, this review suggests microbial signatures that appear across psychiatric diseases, supporting the possibility of shared pathophysiological pathways. Given the largely associative nature of the available data, these findings should be interpreted cautiously and may help guide future research exploring the role of the gut microbiota in mental health.},
}

@article {pmid41847455,
year = {2026},
author = {McFadden, SA and Fang, Y and Quinn, K and Peck, MR and Chapman, JE and Hill, T and Bartke, A and Hascup, ER and Hascup, KN},
title = {Surgical removal of visceral adipose tissue has therapeutic benefit in male APP[NL-F] mice.},
journal = {Frontiers in endocrinology},
volume = {17},
number = {},
pages = {1681801},
pmid = {41847455},
issn = {1664-2392},
mesh = {Animals ; Male ; Mice ; Female ; *Alzheimer Disease/metabolism/surgery/pathology ; *Intra-Abdominal Fat/surgery/metabolism ; Mice, Transgenic ; Insulin Resistance ; Amyloid beta-Protein Precursor/genetics ; Disease Models, Animal ; Lipid Metabolism ; },
abstract = {PURPOSE: Visceral white adipose tissue (vWAT) accumulation causes systemic inflammation, insulin resistance, metabolic syndrome, and senescent cell accumulation that are risk factors for Alzheimer's disease (AD). Visceral fat removal (VFR) improves metabolism and reduces pro-inflammatory cytokines. We hypothesized that VFR removal in AD mice would improve metabolism and cognition.

METHODS: Male and female APP[NL-F] mice underwent sham or vWAT surgical resection (periovarian or epididymal and perirenal) at 4 (pre-symptomatic) and 16 (symptomatic) months of age to understand interventional and therapeutic effects, respectively. At 18 months of age, glucose metabolism and novel object recognition (NOR) memory were assayed followed by assessment of body composition and tissue-specific markers of metabolism, cell senescence, inflammation, or amyloid accumulation.

RESULTS: Male and female APP[NL-F] mice showed distinct VFR responses. In pre-symptomatic males, increased vWAT lipolysis and hepatic lipogenesis led to ectopic liver lipid accumulation, with reduced adiponectin and leptin, elevated visfatin, and impaired glucose metabolism. Symptomatic males showed reduced vWAT lipogenesis, enhanced hepatic lipolysis, glycolysis, and glycogenesis, lowering liver lipids and improving insulin sensitivity. Only symptomatic males improved NOR, linked to elevated hippocampal learning and memory markers. Female vWAT reaccumulation was due to increased lipogenesis and lower lipolysis. Pre-symptomatic females had lower hepatic lipogenesis, while glycolysis and glycogenesis declined with disease progression. Hippocampal senescence and inflammation were elevated early in the disease that persisted symptomatically.

DISCUSSION: Sex-specific differences in glucose and lipid metabolism and lipid accumulation underlie the divergent responses to VFR in APP[NL-F] mice, with symptomatic males showing the only beneficial outcomes in metabolism and cognition.},
}

Animals
Male
Mice
Female
*Alzheimer Disease/metabolism/surgery/pathology
*Intra-Abdominal Fat/surgery/metabolism
Mice, Transgenic
Insulin Resistance
Amyloid beta-Protein Precursor/genetics
Disease Models, Animal
Lipid Metabolism

@article {pmid41847685,
year = {2026},
author = {Si, C and Ma, L and Ding, W and Tian, Y and Zhang, J and Cao, H and Shao, Y and Fan, Z},
title = {Human umbilical cord mesenchymal stem cells therapy for Alzheimer's disease: a systematic review and meta-analysis of mouse models.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1783757},
pmid = {41847685},
issn = {1664-2295},
abstract = {OBJECTIVE: Given the limitations of current treatments for Alzheimer's disease (AD), this study aims to comprehensively evaluate the therapeutic efficacy of human umbilical cord mesenchymal stem cells (hUCMSCs) in AD mouse models through a systematic review and meta-analysis. Additionally, we explore the impact of transplantation dose and route on treatment outcomes to identify the optimal window for clinical application.

METHODS: In accordance with the PRISMA guidelines, we systematically searched four major databases to identify randomized controlled trials involving hUCMSCs in AD mouse models. We used the standardized mean difference (SMD) to synthesize effect sizes and performed subgroup analyses based on pre-defined transplantation routes and doses.

RESULTS: A total of 13 studies were included in the analysis. The meta-analysis revealed that hUCMSCs transplantation significantly improved spatial learning and memory in AD model mice, with a marked reduction in escape latency (SMD = -2.55; 95% CI: -3.34 to -1.75; I [2] = 77.9%, random-effects model). Additionally, it significantly lowered brain β-amyloid levels (SMD = -5.34; 95% CI: -7.21 to -3.47; I [2] = 80.3%), increased brain-derived neurotrophic factor (SMD = 4.25; 95% CI: 3.18 to 5.31), and reduced neuronal apoptosis (SMD = -4.96; 95% CI: -6.52 to -3.41). Subgroup analyses further revealed that efficacy was significantly dose- and route-dependent. For cognitive improvement, intravenous injection of medium to high doses (≥1 × 10[6] cells) was most effective and robust. For amyloid-β clearance, low-dose administration via intravenous, lateral ventricle, and cortical routes showed significant efficacy, whereas bilateral hippocampal injection did not yield significant benefits.

CONCLUSION: Human umbilical cord mesenchymal stem cells can improve behavioral and pathological outcomes in AD mouse models via multiple mechanisms of action. The intravenous route using medium to high doses emerges as a critical factor for achieving optimal effects, providing important evidence and informing future experimental design and clinical translational research.},
}

@article {pmid41847871,
year = {2026},
author = {Singh, LK and Singh, SP and Sharma, P},
title = {Oxidative-stress-responsive polymeric nanocarriers for Alzheimer's disease: emerging antioxidant strategies using NAC and curcumin.},
journal = {Journal of biomaterials science. Polymer edition},
volume = {},
number = {},
pages = {1-37},
doi = {10.1080/09205063.2026.2644503},
pmid = {41847871},
issn = {1568-5624},
abstract = {A complex combination of oxidative stress, mitochondrial dysfunction, neuroinflammation, and protein aggregation initiates Alzheimer disease (AD), and redox imbalance becomes an initial and lead pathological process. Traditional antioxidants like N-acetylcysteine (NAC) and curcumin demonstrate high mechanistic capacity but have poor stability, are rapidly metabolicized and have low blood-brain barrier (BBB) penetration. Polymeric nanocarriers can be a solution to these drawbacks, as they offer controlled delivery, better targeting to the brain, and dynamic delivery in response to microenvironmental changes. This review is a synthesis of recent developments in oxidative-stress-responsive polymeric systems (PLGA-, chitosan-, and hybrid polymer-based nanoparticles) designed to be used in precise redox modulation. We emphasize the therapeutic synergies of co-delivery of dual NAC-curcumin that is backed with in-vitro and in-vivo results of enhanced antioxidant activity, mitochondrial integrity, and cognitive improvements in AD models. The most important translational obstacles such as nanoparticle scalability, regulatory obstacles, and interpatient heterogeneity are acutely addressed, as well as new developments such as AI-driven formulation design and personalized oxidative biomarker profiling. All these innovations put redox-targeted nanomedicine as a prospective next-generation therapy of AD.},
}

@article {pmid41848005,
year = {2026},
author = {Desvarieux, M and Rundek, T and Ahsan, H and Narvaez, J and Diaz, F and Malinsky, D and Ruiz, LM and Topaz, M and Falconer, T and Natarajan, K and Noble, J and Entwisle, B and Puram, D and Anand, T and Chen, HY and Jiang, X and Gu, Y and Cohen, A and Terry, MB and Pierce, B and Andrews, H and Rogalsky, E and Farzana, S and Gulotta, G and Beard, J and Landron, D and Volchenboum, SL and Ravaud, P and Johnson, J and Susser, E and Rundle, A and Wei, Y and Tsinoremas, N and Loewenstein, D and Fried, L and Aiello, A and Mayeux, R and Hripcsak, G},
title = {Accelerating real-world prediction and research in Alzheimer's: The M3AD study.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {3},
pages = {e71174},
doi = {10.1002/alz.71174},
pmid = {41848005},
issn = {1552-5279},
support = {R56AG082167/AG/NIA NIH HHS/United States ; /NH/NIH HHS/United States ; },
mesh = {Humans ; *Alzheimer Disease/epidemiology/diagnosis ; *Electronic Health Records ; Multimorbidity ; Aged ; },
abstract = {Chronic diseases, including Alzheimer's disease (AD) and related dementia (ADRD), do not exist solely as isolated entities. Instead, they weave concomitant trajectories of multiple diseases, conditions, behaviors, and risks, mutually influencing each other's course and natural history, in ways yet unexplored. Electronic health records (EHRs) provide us with a unique opportunity to look at related and unrelated clinical trajectories over time, thus potentially providing insight into unrecognized prodromes, while incorporating the complexities of patients' lives. We harmonize and federate a three-city EHR metaplatform of nearly 10 million patients (∼60,000 with AD/ADRD), which we further embed within census tracts, to contextualize these health trajectories. Our multidisciplinary approach ambitions a unique dynamic platform to inform strategies to tailor risk prediction, complex clinical management, and real-world evaluation of future treatments of AD/ADRD. We present the rationale for and design of the Multimorbidity Three-City Alzheimer's Disease EHR (M3AD) Study and real-world data metaplatform, progress and demonstration of feasibility, its expected singular and complementary contributions to the field. HIGHLIGHTS: Our success in living longer lives often brings chronic conditions and multimorbidity. Alzheimer's research should comprise life trajectories' complexity in multimorbidity. New real-world analytical approaches allow integrated prediction of Alzheimer's disease. We are building a three-city electronic health record (EHR) metaplatform for prediction, prevention, and impact We further embed EHR within census tracts to contextualize Alzheimer's trajectories.},
}

Humans
*Alzheimer Disease/epidemiology/diagnosis
*Electronic Health Records
Multimorbidity
Aged

@article {pmid41848189,
year = {2026},
author = {Shrewsbury, SB},
title = {DHE - past, present, and future: a narrative review.},
journal = {Pain management},
volume = {},
number = {},
pages = {1-15},
doi = {10.1080/17581869.2026.2644524},
pmid = {41848189},
issn = {1758-1877},
abstract = {Dihydroergotamine (DHE) was first approved in 1946 for the acute treatment of migraine. Its efficacy when administered as an intravenous (IV) injection explains its enduring use in the management of migraine today. More recently, attention has been focused on the development of formulations delivered by the inhalational route to either the nasal mucosa or lung with the objective of providing a product that enables easy, needle-free, "at-home" use that is rapidly effective. Three new DHE products for migraine (two administered by nasal delivery) have been Food and Drug Administration (FDA) approved in the past five years with two others using pulmonary delivery in clinical development attempting to optimize outcomes for subjects requiring "at-home" migraine treatment. This narrative review describes those DHE development programs, and others that have failed, with the objective of providing a broad perspective on various approaches, including those that may be more likely to achieve the goals of high efficacy rates, rapid relief, and convenience of use. In addition, DHE has been investigated for potential repurposing of other indications. These too are described.},
}

@article {pmid41848214,
year = {2026},
author = {Jiang, H and Wang, YQ and Dong, XY and Zhao, D and Wei, YY and Liu, ZP and Wang, JD},
title = {Fe-Doped Carbon Dots Functionalized Nanoelectrode for In Situ Monitoring of Metabolism-Associated ROS Changes in Single Microglia.},
journal = {Analytical chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.analchem.5c07646},
pmid = {41848214},
issn = {1520-6882},
abstract = {In metabolic reprogramming, reactive oxygen species (ROS) serve not only as harmful byproducts but also as essential signaling molecules that drive reprogramming processes to establish new metabolic homeostasis. Therefore, the in situ monitoring of ROS changes during metabolic reprogramming is crucial for understanding metabolic changes. Herein, we develop an Fe-doped carbon dots (FeCDs)-functionalized nanoelectrode that exploits the excellent catalytic activity of FeCDs to achieve in situ monitoring of intracellular ROS in single microglia under a neuroinflammatory microenvironment mimicking Alzheimer's disease. Further investigations reveal that cordycepin may target hexokinase II, a key regulatory enzyme in glucose metabolism, thereby inducing metabolic reprogramming in microglia and mitigating the LPS + Aβ-induced elevation in intracellular ROS. This work provides an efficient strategy for in situ monitoring of ROS changes during metabolic reprogramming at the single-cell level, which is vital for advancing disease diagnosis and therapeutic development.},
}

@article {pmid41848292,
year = {2026},
author = {Tropea, TF and Stevenson, PA and Flitter, M and Meehan, D and Morris, A and Lu, M and Iaccarino, L and Collins, EC and Hodsdon, ME and Irwin, D and Spindler, M and Deik, A and Dahodwala, N and Cousins, KAQ and Wolk, DA and Shaw, L and Weintraub, D and Lee, EB and Chen-Plotkin, A and Mintun, M and Siderowf, A},
title = {Association between Plasma P-tau217 and Alzheimer's Copathology and Cognitive Decline in Parkinson's Disease.},
journal = {Annals of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ana.78201},
pmid = {41848292},
issn = {1531-8249},
support = {K23NS114167/GF/NIH HHS/United States ; P30AG072979/GF/NIH HHS/United States ; P50NS053488/GF/NIH HHS/United States ; P30AG010124/GF/NIH HHS/United States ; U19AG062418/GF/NIH HHS/United States ; P01AG084497/GF/NIH HHS/United States ; P01AG066597/GF/NIH HHS/United States ; },
abstract = {OBJECTIVE: Clinically relevant Alzheimer's disease co-pathology is common in Lewy body disorders. Plasma P-tau217 is a sensitive biomarker for amyloid and tau pathology in Alzheimer's disease. The objective was to determine if plasma P-tau217 associates with Alzheimer's disease co-pathology and cognition in Lewy body disorders.

METHODS: Participants had (1) a clinicopathological diagnosis of Parkinson's disease or dementia with Lewy bodies in the pathology series, or (2) a clinical diagnosis of Parkinson's disease in the clinical series and were followed as part of the longitudinal, observational cohort study at the University of Pennsylvania between 2007 and 2024. Plasma concentration of P-tau217 was measured in previously collected samples.

RESULTS: Neuropathology cases included 46 Parkinson's disease and 10 dementia with Lewy bodies, and clinical cases included 173 Parkinson's disease, and 64 controls. P-tau217 was greater in cases with (median, 0.3 [interquartile range (IQR), 0.2-0.4]) versus without (median, 0.1 [IQR, 0.1-0.2]) Alzheimer's disease co-pathology (p < 0.01) and discriminates Lewy body disorders participants with Alzheimer's disease co-pathology (area under curve, 0.84). Parkinson's disease participants with incident cognitive impairment had greater increases in serial P-tau217 than those who remained cognitively stable (group × time interaction β = -0.010, p = 0.0027). Higher baseline P-tau217 concentrations associated with longitudinal change in dementia rating scale (group × time interaction β = -4.947, p = 0.0166) and higher risk for cognitive progression (hazard ratio = 1.597, p = 0.003).

INTERPRETATION: Plasma P-tau217 detects Alzheimer's disease co-pathology in Lewy body disorders and predicts cognitive decline. Future studies will evaluate associations between plasma P-tau217 and imaging and clinical outcomes, in consideration for use of amyloid-targeting therapies in Lewy body disorders. ANN NEUROL 2026.},
}

@article {pmid41848374,
year = {2026},
author = {Canet, G and Lucey, BP and Blessing, EM and Planel, E},
title = {Lifelong heat exposure as a potential contributor to Alzheimer's disease resilience.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261433226},
doi = {10.1177/13872877261433226},
pmid = {41848374},
issn = {1875-8908},
abstract = {A recent case study reported a PSEN2 mutation carrier with high amyloid burden but unexpectedly restricted tau pathology and preserved cognition. While genetic and proteomic factors were explored, the patient's lifelong occupational heat exposure may represent an overlooked contributor to resilience. We highlight evidence from preclinical, clinical, and epidemiological studies suggesting that elevated body temperature promotes tau clearance via enhanced proteostasis. This observation invites deeper investigation into thermoregulation as a modifiable factor in tau homeostasis and Alzheimer's disease vulnerability, with implications for both biomarker interpretation and therapeutic strategies targeting tau-mediated neurodegeneration.},
}

@article {pmid41848375,
year = {2026},
author = {Pandey, JP and Namboodiri, AM and Nietert, PJ},
title = {Immunoglobulin allotypes and RELN alleles and humoral immunity to HSV1 in patients with Alzheimer's disease and matched controls.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261431862},
doi = {10.1177/13872877261431862},
pmid = {41848375},
issn = {1875-8908},
abstract = {BackgroundIncreasing evidence implicates herpes simplex virus type 1 (HSV1) in the pathogenesis of Alzheimer's disease (AD). The genome-wide association studies have not detected any genes regulating antibody responses to HSV1.ObjectiveTo determine whether the magnitude of antibody responses to HSV1 and to its glycoprotein D (gD) differed between AD patients and controls. Using a candidate gene approach, determine if the antibody responses were associated with immunoglobulin GM (γ marker) and KM (κ marker) allotypes-hereditary antigenic determinants of γ and κ chains, respectively. We also aimed to determine whether GM and KM allotypes epistatically interacted with an AD risk gene-reelin-encoding RELN (rs2299356)-and contributed to immunity to HSV1 and HSV1-gD.MethodsGenotyping was done by polymerase chain reaction-restriction fragment length polymorphism, TaqMan[®], and rhAMP[®] SNP genotyping assays. IgG antibodies to HSV1 and HSV1-gD were measured by an enzyme-linked immunosorbent assay.ResultsAnti-HSV1 antibody levels were not significantly different between AD cases and controls; however, anti-HSV1-gD antibody levels were over two-fold higher (p < 0.0001) in AD cases compared to controls. GM 23 allele was associated with higher anti-HSV1 antibody levels in both cases and controls. Potential interaction between KM and RELN rs2299356 alleles on antibody responses to HSV1-gD was detected in AD cases, but not in controls.ConclusionsIn view of the fact that HSV1-gD is a vaccine candidate, the findings of higher anti-HSV1-gD antibody levels in AD patients and potential interaction of KM and RELN rs2299356 alleles in this study warrant additional large-scale multiethnic studies on this issue.},
}

@article {pmid41848386,
year = {2026},
author = {Messaoudi, SA and Alsaleh, A and AlSalem, LA and Rameshbabu, S and Kumar, S and Assidi, M and Ouanes, K and Chayeb, V and Zitouni, H and Almawi, WY},
title = {Association of genetic variants in cyclin-dependent kinase 5 with Alzheimer's disease in a Saudi cohort.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261427358},
doi = {10.1177/13872877261427358},
pmid = {41848386},
issn = {1875-8908},
abstract = {BackgroundCyclin-dependent kinase 5 (CDK5) plays a critical role in neuronal development, synaptic plasticity, and cytoskeletal regulation. Its dysregulation has been implicated in Alzheimer's disease (AD); however, supporting genetic evidence remains limited in Middle Eastern populations.ObjectiveThis study aimed to identify CDK5 genetic variants in a Saudi cohort with AD and evaluate their association with disease susceptibility, without addressing downstream functional mechanisms.MethodsPeripheral blood samples were obtained from 52 Saudi patients with AD and 60 age- and sex-matched healthy controls. Genomic DNA was extracted and quantified using a NanoDrop One spectrophotometer. CDK5 exons 1, 2, 6, 7, and 12 were amplified and sequenced by Sanger methodology on an ABI 3500 Genetic Analyzer. Variant screening and frequency comparisons were performed between dementia and control groups.ResultsEight CDK5 variants were identified in exonic (2, 12) and intronic (1-2, 7-8, 11-12) regions, including three novel variants (c.105delG, c.858C > T, and one intronic variant). No variants were detected in exons 1, 6, or 7. Frameshift variants c.103del and c.105delG were significantly more frequent in AD cases (38%) than controls (5%) (p < 0.001). Conversely, the synonymous c.855C > T variant (Exon 12) was more common in controls (23%) than cases (5%) (p < 0.01), indicating a significant association between specific CDK5 variants and AD.ConclusionsIdentification of novel CDK5 variants associated with AD in a Saudi cohort highlights population-specific genetic susceptibility. Further functional and biomarker studies are needed to clarify their biological relevance.},
}

@article {pmid41848387,
year = {2026},
author = {Pečar Fonović, U and Kralj, S and Kos, J},
title = {Amyloid-β 1-42 fibrils regulate SH-SY5Y cell adhesion in a delayed manner.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261429855},
doi = {10.1177/13872877261429855},
pmid = {41848387},
issn = {1875-8908},
abstract = {Amyloid-β peptide (Aβ), a hallmark peptide in the pathology of Alzheimer's disease, together with the amyloid-β protein precursor, is increasingly associated with the disruption of cell adhesion. In addition to its well-characterized role in plaque formation and synaptic dysfunction, Aβ interacts with various adhesion molecules and extracellular matrix components, thereby impairing neuronal connectivity and integrity. We have shown that pretreatment of SH-SY5Y cells with Aβ42 fibrils affects cell adhesion; however, we did not observe this effect with Aβ42 monomers. Understanding the molecular mechanisms by which Aβ fibrils disrupt cell adhesion pathways may reveal new therapeutic approaches to prevent disease progression.},
}

@article {pmid41848390,
year = {2026},
author = {Urian, DM and Gupta, G and Battista, ME and Wild, CJ and Owen, AM},
title = {Early cognitive screening for individuals on the dementia continuum: A novel approach amid current trends.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261424289},
doi = {10.1177/13872877261424289},
pmid = {41848390},
issn = {1875-8908},
abstract = {Mild cognitive impairment (MCI) is a critical transitional stage between normal aging and dementia that remains challenging to detect. Many traditional neuropsychological assessments designed for early detection of MCI are time-consuming, require specialized training and/or demonstrate limited validity, making them impractical for widespread use in primary care settings. This article is divided into two phases. The first phase provides a rapid review of the current landscape of cognitive screening tools, while the second presents a novel, fully automated, digital screener based on two tasks from the Creyos cognitive assessment platform. This novel screener has been designed, using machine learning, for rapid administration without clinical supervision. The preliminary findings demonstrate that our two-task screener effectively differentiates between cognitively normal individuals and those at risk of progression along the Alzheimer's disease continuum. Furthermore, validation analyses showed that the screener has high sensitivity and specificity, outperforming many conventional assessments. By offering a brief, accessible, and reliable alternative to standard screening tools, our screener has the potential to enhance early detection efforts and facilitate timely intervention, ultimately improving patient outcomes, reducing the burden on clinicians, and optimizing healthcare resources.},
}

@article {pmid41848403,
year = {2026},
author = {Karagöz, AD and Kocamaz, D and Uysal, SA},
title = {Are YouTube Videos a Reliable Source of Information About Exercise in Alzheimer's Disease?.},
journal = {Australasian journal on ageing},
volume = {45},
number = {1},
pages = {e70149},
doi = {10.1111/ajag.70149},
pmid = {41848403},
issn = {1741-6612},
mesh = {Humans ; *Alzheimer Disease/diagnosis/therapy/psychology/physiopathology ; *Social Media ; *Video Recording ; Reproducibility of Results ; *Consumer Health Information/methods/standards ; *Exercise ; *Information Dissemination/methods ; Health Knowledge, Attitudes, Practice ; *Patient Education as Topic/methods ; Information Sources ; },
abstract = {OBJECTIVE: The rapid growth in the use of online platforms for obtaining health-related information, together with the increasing incidence of Alzheimer's disease (AD), has made the evaluation of online information quality essential. The purpose of this research was to assess the quality and reliability of the more likely to be viewed YouTube videos related to exercise in individuals living with AD.

METHODS: This descriptive study evaluated the quality and reliability of YouTube videos related to AD and exercise. Fifty-six English language videos were selected from the top search results based on keywords. Video sources, view rate metrics and content characteristics were recorded. The quality and reliability of the videos were independently evaluated by three physiotherapists using the Global Quality Scale (GQS) and DISCERN tool.

RESULTS: High-quality videos had higher DISCERN scores and greater view rate (p = 0.02), whereas low-quality videos showed minimal interaction (p < 0.001). Dislike rates were similar across all groups. In addition, Pearson correlation analysis indicated a very strong positive relationship (r = 0.97, p < 0.001) between views and likes, indicating that more viewed videos tend to receive more likes.

CONCLUSIONS: Video quality may have an influence on both the reliability of the information and viewer interaction, as reflected by view and like metrics. A considerable number of YouTube videos on exercise for individuals living with AD were shown to be of low or moderate quality. The findings highlight the need for improved oversight, collaboration between healthcare professionals and content creators, and the promotion of evidence-based digital health information to protect vulnerable populations.},
}

Humans
*Alzheimer Disease/diagnosis/therapy/psychology/physiopathology
*Social Media
*Video Recording
Reproducibility of Results
*Consumer Health Information/methods/standards
*Exercise
*Information Dissemination/methods
Health Knowledge, Attitudes, Practice
*Patient Education as Topic/methods
Information Sources

@article {pmid41848619,
year = {2026},
author = {Morita, K and Seguchi, S and Hayashi, A and Miwa, H and Uchida, S and Sugimoto, K and Chatani, E and Tamura, A and Maruyama, T},
title = {A Chirality-Guided Molecular Recognition Strategy for Targeting Intrinsically Disordered Proteins.},
journal = {Chemistry (Weinheim an der Bergstrasse, Germany)},
volume = {},
number = {},
pages = {e70889},
doi = {10.1002/chem.70889},
pmid = {41848619},
issn = {1521-3765},
support = {2022S230//Nakatani Foundation for Advancement of Measuring Technologies in Biomedical Engineering/ ; //Toyota Physical and Chemical Research Institute/ ; RS2408//NORITZ Nukumori Foundation/ ; //Koyanagi Zaidan/ ; //Canon Foundation/ ; //Suzuken Memorial Foundation/ ; 24ek0109691//Japan Agency for Medical Research and Development/ ; 24ym0126808j0003//Japan Agency for Medical Research and Development/ ; 23H01774//JSPS KAKENHI/ ; 23K13610//JSPS KAKENHI/ ; },
abstract = {Some peptide sequences are known to interact with their enantiomers to form stereocomplexes. However, the sequence-dependent conditions required for stereocomplexation have not been thoroughly elucidated. Here, we present a systematic investigation of peptide stereocomplexation using short tripeptides and their enantiomers. Stereocomplexation was evaluated by aggregate formation in mixed aqueous solutions, and single-crystal X-ray diffraction revealed racemic crystals. Stereocomplexation was driven by hydrophobic interactions between phenylalanine residues and electrostatic interactions involving lysine and the C-terminus. Thermodynamic and structural features of the complexation were further elucidated by calorimetry, simulations, and fluorescence assays. On the basis of these insights, a D-peptide (Ac-fffakr5-NH2) was rationally designed to target the -FFAE- motif of amyloid β42 (Aβ42), a pathological intrinsically disordered protein. This D-peptide inhibited the fibrillization and cytotoxicity of Aβ42 in neuronal-like cells, outperforming a clinical candidate, peptide drug RD2. These findings establish peptide stereocomplexation as a viable strategy for constructing sequence-targeting ligands even against intrinsically disordered proteins.},
}

@article {pmid41848850,
year = {2026},
author = {Zhang, L and Luo, X},
title = {Higher educational attainment, accelerated tau, and slower decline: unraveling the Alzheimer's paradox.},
journal = {European radiology},
volume = {},
number = {},
pages = {},
pmid = {41848850},
issn = {1432-1084},
}

@article {pmid41848892,
year = {2026},
author = {Verma, M and Singh, NK},
title = {From bench to bedside: Emerging therapeutics for alzheimer's disease in clinical trials.},
journal = {Metabolic brain disease},
volume = {41},
number = {1},
pages = {},
pmid = {41848892},
issn = {1573-7365},
}

@article {pmid41848904,
year = {2026},
author = {Zheng, H and Si, M and Wang, Q},
title = {Correlation between thyroid hormone levels and cognitive dysfunction in older patients with subclinical hypothyroidism : A matched groups retrospective study.},
journal = {Wiener klinische Wochenschrift},
volume = {},
number = {},
pages = {},
pmid = {41848904},
issn = {1613-7671},
abstract = {OBJECTIVE: To investigate the correlation between thyroid hormone levels and cognitive dysfunction in older patients with subclinical hypothyroidism (SCH).

METHODS: A retrospective matched case-control study (1:2 ratio) was conducted, enrolling 420 participants aged ≥ 60 years (140 SCH cases, 280 euthyroid controls) matched by gender, age (± 5 years) and education level. Thyroid function parameters, including thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb), and cognitive performance assessed via the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), Auditory Verbal Learning Test (AVLT), Trail Making Test (TMT), and Stroop Color and Word Test (Stroop Test) were measured.

RESULTS: The SCH patients had TSH levels consistent with the grouping criteria (TSH > 4.2 mIU/L), higher thyroid autoantibody positivity, and poorer cognitive performance across all domains (all P < 0.001). A dose-response relationship was observed between increasing TSH levels and worsening cognitive function. Multivariate logistic regression identified TSH (odds ratio, OR = 1.19), FT3 (OR = 0.68), age, education and APOE ε4 carrier status as independent predictors of cognitive impairment (ROC AUC = 0.786). Stratified analyses showed stronger associations in females and those aged < 75 years, whereas the significance of the correlation between TSH and cognitive impairment was lost in patients aged ≥ 75 years. Sensitivity analyses confirmed the robustness of the findings.

CONCLUSION: The SCH is independently associated with cognitive dysfunction in older people, with thyroid hormones playing a critical role. The findings suggest potential clinical implications for thyroid function monitoring and cognitive protection in this population.},
}

@article {pmid41848983,
year = {2026},
author = {Tsai, MY},
title = {Visualizing Somaesthetics and Destigmatizing Embodied Caregiving in Tangles and Special Exits.},
journal = {The Journal of medical humanities},
volume = {},
number = {},
pages = {},
pmid = {41848983},
issn = {1573-3645},
support = {NSTC 113-2410-H-194-004//National Science and Technology Council/ ; },
abstract = {This essay explores how graphic memoirs reshape our understanding of physical care by portraying it not as menial labor but as a form of somatic creativity that blends ethical intention with aesthetic sensitivity. Drawing on Richard Shusterman's somaesthetics and Felicity Aulino's rituals of care, it examines Sarah Leavitt's Tangles: A Story About Alzheimer's, My Mother, and Me (2012) and Joyce Farmer's Special Exits: A Graphic Memoir (2010) to show how both works transform caregiving from a stigmatized task into a model of empathetic exchange by challenging the social stigma that devalues intimate bodily care as degrading "dirty work" and equates dependency with a loss of dignity. While unflinchingly depicting the difficult realities of embodied care, Tangles and Special Exits reimagine it as an artistic collaboration between caregiver and cared-for-a practice that affirms dignity and creative potential. Through their distinctive visual and narrative sensitivity, these graphic care memoirs illuminate the sensory and ritual dimensions of caregiving, presenting it as an ethical and aesthetic practice vital to sustaining human connection. In doing so, they issue a powerful call for systemic change, urging a cultural revaluation of embodied care as a practice grounded in creativity, reciprocity, and shared vulnerability.},
}

@article {pmid41849679,
year = {2026},
author = {Su, J and Yang, M and Wang, X and Wu, P and Zhai, Z},
title = {Intracellular Aβ42 Sequestration by a Serine Protease Mitigates Neurotoxicity in a Drosophila Alzheimer's Disease Model.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e17862},
doi = {10.1002/advs.202517862},
pmid = {41849679},
issn = {2198-3844},
support = {32170509//NSFC/ ; 2025JJ30009//Hunan NSF/ ; 2022XKQ0203//Key Project of Developmental Biology and Breeding from Hunan Province/ ; 143010100//Key Project of Developmental Biology and Breeding from Hunan Province/ ; },
abstract = {Emerging evidence suggests that intraneuronal Aβ accumulation represents an early pathogenic event in Alzheimer's disease (AD), preceding extracellular plaque formation and neuroinflammatory responses. However, whether targeting intracellular Aβ can halt disease progression and how this can be achieved in vivo remain unknown. While investigating the brain transcriptional responses to Aβ pathology, we identify a neuroprotective role for the serine protease Yip7 in a Drosophila AD model. Neuronal overexpression of yip7 alleviates multiple Aβ42-induced deficits, including declines in locomotor activity, impaired proteostasis, increased brain aging and neuronal death, and shortened lifespan. Unlike canonical digestive proteases, Yip7 is not secreted but instead localized to the endosomal/lysosomal compartments via a putative transmembrane domain initially predicted as a signal peptide. Crucially, Yip7's neuroprotective function depends on its proper subcellular localization rather than the catalytic triad. Mechanistically, rather than eliminating Aβ, Yip7 binds intracellular Aβ42 to increase its neuronal retention, and this unexpectedly reduces Aβ42 toxicity to the organism. Finally, transcriptomics reveals that protection against Aβ42 toxicity by Yip7 is associated with selective suppression of Aβ-upregulated genes including those codingribosomal proteins and molecular chaperones for protein folding. Together, these findings introduce a novel concept that intracellular sequestration of Aβ can be explored to mitigate its neurotoxicity.},
}

@article {pmid41849872,
year = {2026},
author = {Wang, Q and Lv, M and Zhou, X and Chen, Z and Zhou, X and Wu, Q and Li, A and He, W and Xia, J},
title = {Association of choroid plexus volume with MRI indices of DTI-derived parameters and perivascular spaces in patients with neurodegenerative diseases.},
journal = {European journal of radiology},
volume = {199},
number = {},
pages = {112798},
doi = {10.1016/j.ejrad.2026.112798},
pmid = {41849872},
issn = {1872-7727},
abstract = {OBJECTIVE: To compare the association between CP volume fraction (CPVF) and glymphatic function (assessed by perivascular space volume fraction [PVSVF], white matter free water fraction [FW-WM], and diffusion tensor imaging analysis along perivascular spaces [DTI-ALPS]) in patients with Alzheimer's disease (AD), Parkinson's disease (PD), idiopathic normal pressure hydrocephalus (iNPH), and healthy controls (HCs), and explore the utility of multiparametric MRI integration for differential diagnosis.

PATIENTS AND METHODS: This single-centre cohort study included 33 iNPH patients, 42 AD patients, 49 PD patients, and 30 HCs. Group differences in 3.0-T MRI parameters were assessed using a general linear univariate model adjusted for age and sex. Partial correlation analysis was performed to evaluate correlations between CPVF and glymphatic parameters in each group. A composite score combining the four MRI parameters was generated via multiple logistic regression, with diagnostic performance evaluated using receiver operating characteristic curves.

RESULTS: Patients with iNPH, AD, and PD showed significantly higher CPVF, FW-WM, and MRI-PVS and lower DTI-ALPS than HCs (all p < 0.001). iNPH involved significantly higher CPVF and lower FW-WM and DTI-ALPS than AD or PD (all p < 0.001). In PD, CPVF was significantly negatively correlated with DTI-ALPS (r =  - 0.509, p fdr = 0.003), while CPVF also showed a significant positive correlation with FW-WM (r = 0.532, pfdr = 0.003). Additionally, the AUC of the composite score indicated good performance in differentiating iNPH from AD and PD (AUC = 0.902 and 0.96, respectively).

CONCLUSION: MRI indices of CSF dynamics and glymphatic function exhibit disease-specific patterns, with unique inter-relationships in PD.},
}

@article {pmid41849958,
year = {2026},
author = {Iwata, A and Sakata, Y and Koizumi, K and Endo, A and Kuang, W and Sumitomo, K and Ishii, M},
title = {Interim analysis of all-case post-marketing surveillance study in Japan: lecanemab in patients with early Alzheimer's disease.},
journal = {The journal of prevention of Alzheimer's disease},
volume = {13},
number = {5},
pages = {100541},
doi = {10.1016/j.tjpad.2026.100541},
pmid = {41849958},
issn = {2426-0266},
abstract = {BACKGROUND: Lecanemab is a monoclonal antibody targeting amyloid-beta protofibrils, indicated for patients with mild cognitive impairment (MCI) and mild dementia due to Alzheimer's disease.

OBJECTIVES: This study reports interim findings of an ongoing, multicenter, prospective, observational post-marketing study for all patients treated with lecanemab in routine clinical practice in Japan, focusing on amyloid-related imaging abnormalities (ARIAs) and infusion-related reactions primarily observed during up to 28 weeks after treatment initiation.

METHODS: Patients treated with lecanemab at any medical institutions across Japan are included in the study. Data are collected using an electronic data capture system via standardized case report forms (CRFs). Study items included the incidence of ARIA, ARIA-edema or effusion (-E), ARIA-hemorrhage (-H: cerebral microhemorrhages, superficial siderosis, and macrohemorrhage), and infusion-related reactions, reported as adverse drug reactions.

RESULTS: As of July 5, 2025, CRFs from 2675 patients were collected, of whom 2672 had data available for the interim analysis. The median age was 76.0 years, and 62.6 % (1672/2672) of patients were diagnosed with MCI. At Week 28, 7.3 % (195/2672) of patients discontinued treatment, with a mean treatment duration of 189.6 ± 34.4 days. Among 2634 patients confirmed to have undergone MRI scans after treatment initiation, ARIA was observed in 7.1 % (188/2634) of patients, ARIA-E in 3.0 % (78/2634), and ARIA-H in 5.2 % (137/2634). Serious ARIA-H (macrohemorrhage) occurred in two patients (0.1 %). Infusion-related reactions were observed in 17.0 % (455/2672), including 0.7 % (18/2672) serious cases. The proportion of patients who experienced ARIA was highest in patients with apolipoprotein E (APOE) ε4 homozygotes.

CONCLUSION: This interim analysis represents one of the largest real-world lecanemab cohorts reported globally to date. Although absolute rates are not directly comparable with those from clinical trials, the trends in ARIA distributions across APOE genotypes and infusion-related reactions were comparable to those observed in clinical trials.},
}

@article {pmid41850230,
year = {2026},
author = {Zou, Y and Sang, Y and Zheng, M and Shi, B},
title = {Blood-brain barrier-penetrative lipid nanoparticles enable systemic delivery of TRIM11 mRNA to disaggregate Tau in Alzheimer's disease models.},
journal = {Cell reports. Medicine},
volume = {7},
number = {3},
pages = {102685},
doi = {10.1016/j.xcrm.2026.102685},
pmid = {41850230},
issn = {2666-3791},
mesh = {*Alzheimer Disease/metabolism/pathology/genetics/therapy ; Animals ; *Blood-Brain Barrier/metabolism ; *tau Proteins/metabolism ; *Nanoparticles/chemistry ; *Tripartite Motif Proteins/genetics/metabolism ; Mice ; Disease Models, Animal ; *RNA, Messenger/metabolism/genetics/administration & dosage ; Humans ; *Ubiquitin-Protein Ligases/genetics/metabolism ; Mice, Transgenic ; Male ; Neurons/metabolism ; Liposomes ; },
abstract = {Hyperphosphorylated Tau aggregates are a central pathological hallmark of Alzheimer's disease (AD), yet no approved therapy directly targets this process. mRNA therapeutics provide a transient and non-viral option but are limited by the blood-brain barrier (BBB). TRIM11 is an ATP-independent disaggregase that dissolves pathological Tau fibrils and promotes proteasomal clearance. Here, a ligand-free lipid nanoparticle (PLNP) is developed with zwitterionic, acetylcholine-mimetic poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) as a core component and leverages interactions with nAChRs and chTs to enable BBB transcytosis. Systemic PLNP delivery of TRIM11 mRNA yields an 8.1-fold increase in hippocampal accumulation and >30-fold higher neuronal transfection than unformulated mRNA. In 3×Tg-AD mice, PLNP-mTRIM11 reduces P-Ser396- and AT8-positive Tau aggregates, attenuates neuroinflammation, restores synaptic/neuronal integrity, and improves cognition and nest building for ≥3 months. Early prophylactic dosing prevents Tau pathology and preserves cognitive function, supporting PLNP-mTRIM11 for tauopathy therapy.},
}

*Alzheimer Disease/metabolism/pathology/genetics/therapy
Animals
*Blood-Brain Barrier/metabolism
*tau Proteins/metabolism
*Nanoparticles/chemistry
*Tripartite Motif Proteins/genetics/metabolism
Mice
Disease Models, Animal
*RNA, Messenger/metabolism/genetics/administration & dosage
Humans
*Ubiquitin-Protein Ligases/genetics/metabolism
Mice, Transgenic
Male
Neurons/metabolism
Liposomes

@article {pmid41850459,
year = {2026},
author = {Li, S and Wei, S and Wang, L and Yu, T and Wang, H and Yang, SB and Cao, W and Zhang, X},
title = {Role of astrocyte biomarker GFAP in early diagnosis and prognosis assessment of dementia: A comprehensive review.},
journal = {International journal of biological macromolecules},
volume = {},
number = {},
pages = {151452},
doi = {10.1016/j.ijbiomac.2026.151452},
pmid = {41850459},
issn = {1879-0003},
abstract = {As a key component of the neurovascular unit, astrocytes play an important role in dementia. They regulate cerebral blood flow, promote myelin regeneration, and maintain central nervous system (CNS) homeostasis. However, glial fibrillary acidic protein (GFAP), a biomarker of reactive astrocytes and an emerging indicator of dementia, has often been overlooked. There is still a lack of systematic reviews on its clinical progress in early diagnosis and prognosis assessment of dementia. This review first explores the pathophysiological mechanisms of astrocytes in dementia and describes the biological characteristics of GFAP. We then summarize the role of GFAP in early diagnosis and prognosis of different dementia types, including Alzheimer's disease (AD), vascular dementia (VaD), and frontotemporal dementia (FTD), with a focus on advances in AD research. We also discuss the latest GFAP detection technologies, such as SIMOA and Lumipulse, and issues like differences between plasma and CSF GFAP measurements. This review aims to provide a comprehensive understanding of GFAP's role in dementia research and clinical practice, offering a theoretical basis for developing more effective diagnostics and therapies.},
}

@article {pmid41850554,
year = {2026},
author = {Guo, J and Xiao, S and Chu, X and Zhao, S and Meng, J and Geng, C and Kong, Z and Zhang, W and Jiang, P},
title = {Multi-Omics Analysis Reveals Alcohol exposure affects Ferroptosis pathway in Brain.},
journal = {Alcohol (Fayetteville, N.Y.)},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.alcohol.2026.03.005},
pmid = {41850554},
issn = {1873-6823},
abstract = {Alcohol-related brain damage (ARBD) constitutes a major global public health issue and is often comorbid with neuropsychiatric disorders such as Alzheimer's and Parkinson's diseases. Ferroptosis, a form of regulated cell death characterized by iron dependency and lipid peroxidation, has been implicated in the pathogenesis of various neurodegenerative disorders. However, the role and underlying mechanisms of ferroptosis in mediating ARBD and its associated neuropsychiatric dysfunctions remain largely unexplored. This study aimed to investigate whether chronic alcohol exposure induces neurodegenerative-like behavioral phenotypes in mice and to identify associated molecular alterations using a multi-omics approach. Behavioral assessments demonstrated that chronic alcohol exposure led to impairments in memory, exploratory activity, and motor coordination. Histopathological analysis revealed significant neuronal damage in the hippocampus and prefrontal cortex. Integrated proteomic and metabolomic profiling identified a significant enrichment of pathways related to ferroptosis and neurodegenerative diseases in alcohol-exposed mice. Additionally, biochemical assays further confirmed alcohol induced disruption of iron homeostasis, elevated reactive oxygen species, and disruption of lipid peroxidation-key features consistent with ferroptosis activation. Taken together, these findings indicate that chronic alcohol exposure induces behavioral deficits and neuronal injury in mice, and is associated with molecular and biochemical changes indicative of ferroptosis. This multi-omics evidence suggests ferroptosis as a plausible contributing pathway in alcohol-related brain damage, offering new directions for understanding its pathophysiology.},
}

@article {pmid41850568,
year = {2026},
author = {Holleman, J and Toopchiani, S and Robinson, O and Kåreholt, I and Kivipelto, M and Middleton, L and Solomon, A and Udeh-Momoh, CT and Sindi, S},
title = {Associations of cortisol with Alzheimer's disease fluid and neuroimaging biomarkers: A systematic review.},
journal = {Frontiers in neuroendocrinology},
volume = {},
number = {},
pages = {101246},
doi = {10.1016/j.yfrne.2026.101246},
pmid = {41850568},
issn = {1095-6808},
abstract = {BACKGROUND: Chronic stress triggers the dysregulation of hypothalamic-pituitary-adrenal (HPA) axis which is characterized by altered diurnal cortisol patterns and increased basal cortisol levels. This dysregulation has been found in Alzheimer's Disease (AD), but its link with AD-related biomarkers remains underexplored. This systematic review aims to synthesize the current knowledge regarding the association between cortisol and biomarkers related to AD.

METHODS: Keywords and phrases related to cortisol and AD-related biomarkers were used to search the MEDLINE database via PubMed and OVID interfaces up to January 2024. Studies focused on the association between cortisol levels and genetic, neuroimaging, and fluid biomarkers related to AD. Additionally, sex differences in the associations between cortisol and AD-related markers were explored.

RESULTS: A total of 2465 studies were identified, 54 of which were included in the systematic review. Most included studies were cross-sectional (91%), and measured blood (51.9%) or salivary (44%) cortisol. Only 6.8% of studies had reported on sex differences. Studies assessing the relationship between diurnal cortisol patterns and novel AD-related biomarkers remain scarce. Elevated cortisol levels tended to be associated with AD-related biomarkers, although associations were dependent on the cortisol measurement strategy and study populations.

CONCLUSION: Findings have been mixed, partly due to differences in cortisol measurement methodologies, including the timing and source of cortisol assessment. More longitudinal studies are needed to determine whether cortisol dysregulation preceded pathological changes related to AD.},
}

@article {pmid41850724,
year = {2026},
author = {Bokros, M and Grunfeld, A and Balukoff, NC and Bouviere, J and Beurel, E and Lee, S},
title = {Enzymes of physiological amyloidogenesis control pathological amyloid toxicity.},
journal = {Life science alliance},
volume = {9},
number = {6},
pages = {},
doi = {10.26508/lsa.202503493},
pmid = {41850724},
issn = {2575-1077},
mesh = {Animals ; Caenorhabditis elegans/metabolism/genetics ; Mice ; *Amyloid beta-Peptides/metabolism/toxicity ; alpha-Synuclein/metabolism ; Disease Models, Animal ; Humans ; Alzheimer Disease/metabolism ; *Amyloid/metabolism/toxicity ; Caenorhabditis elegans Proteins/metabolism/genetics ; Parkinson Disease/metabolism ; },
abstract = {Physiological amyloidogenesis drives the formation of functional amyloids involved in various biochemical pathways. We recently showed that the RNA tailing and decay machinery controls the maturation of intracellular amyloid-like aggregates. This raises the question of whether enzymes that participate in the maturation of physiological amyloids are involved in pathological amyloidogenesis implicated in human proteopathies. Using Caenorhabditis elegans and mouse models of pathological amyloids, we show that manipulating the RNA tailing-decay axis alters the toxicity of β-amyloid and α-synuclein involved in Alzheimer's and Parkinson's diseases, respectively. The RNA tailing enzymes TENT4b and TENT2 protect against β-amyloid- and α-synuclein-induced toxicity by facilitating the formation of nontoxic amyloidogenic assemblies. In contrast, the RNA exonuclease Exosc10 potentiates pathological amyloid toxicity. Remarkably, Exosc10 depletion prevents cognitive decline and restores memory in two different mouse models of β-amyloid neurotoxicity. Taken together, these results suggest that pathways of physiological amyloidogenesis participate in pathological amyloid etiology.},
}

Animals
Caenorhabditis elegans/metabolism/genetics
Mice
*Amyloid beta-Peptides/metabolism/toxicity
alpha-Synuclein/metabolism
Disease Models, Animal
Humans
Alzheimer Disease/metabolism
*Amyloid/metabolism/toxicity
Caenorhabditis elegans Proteins/metabolism/genetics
Parkinson Disease/metabolism

@article {pmid41850980,
year = {2026},
author = {Zhang, Y and Liu, S and Cao, D and Zhao, M and Lu, H and Wang, P},
title = {Corrigendum to "Rg1 improves Alzheimer's disease by regulating mitochondrial dynamics mediated by the AMPK/Drp1 signaling pathway" [J. Ethnopharmacol. 340 (2025) 119285].},
journal = {Journal of ethnopharmacology},
volume = {},
number = {},
pages = {120505},
doi = {10.1016/j.jep.2025.120505},
pmid = {41850980},
issn = {1872-7573},
}

@article {pmid41851031,
year = {2026},
author = {Sun, J and Zufiria-Gerbolés, B and Passaretti, M and Volpe, G and Mijalkov, M and Pereira, JB and , },
title = {Tracking early cognitive decline in preclinical AD with brain MRI similarity.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {3},
pages = {e71170},
doi = {10.1002/alz.71170},
pmid = {41851031},
issn = {1552-5279},
support = {2025-03210//Swedish Research Council/ ; FO2025-0059//Swedish Brain Foundation/ ; 2-3980/2025//Blomqvist Foundation/ ; //StratNeuro/ ; 760250/28.12.2023//Romanian Government through Romania's National Recovery Romania's National Recovery and Resilience Plan (Romanian Ministry of Research, Innovation and Digitalization under Component 9, Investment 8)/ ; PNRR-C9-I8-CF109/31.07.2023//Romanian Government through Romania's National Recovery Romania's National Recovery and Resilience Plan (Romanian Ministry of Research, Innovation and Digitalization under Component 9, Investment 8)/ ; //KID funding/ ; //KI Consolidator Grant/ ; //King Gustaf V and Queen Victoria's Foundation/ ; //Gamla Tjänarinnor/ ; //Gun och Bertil Stohnes Stiftelse/ ; //Dementia Foundation/ ; //Lars Hierta Memorial Foundation/ ; AF-1032782//Alzheimer Foundation/ ; },
mesh = {Humans ; *Alzheimer Disease/diagnostic imaging/pathology ; *Magnetic Resonance Imaging ; *Cognitive Dysfunction/diagnostic imaging/pathology ; Male ; Female ; *Brain/pathology/diagnostic imaging ; Aged ; Biomarkers/cerebrospinal fluid ; Neuroimaging ; Prodromal Symptoms ; Aged, 80 and over ; Amyloid beta-Peptides/cerebrospinal fluid ; Early Diagnosis ; Disease Progression ; },
abstract = {INTRODUCTION: Early detection of neuroanatomical changes in preclinical Alzheimer's disease (AD) is critical for timely intervention. However, conventional magnetic resonance imaging (MRI) and fluid biomarkers often lack sensitivity to subtle structural alterations in early disease stages.

METHODS: To identify early brain alterations, we applied a perturbation-based brain similarity approach to cognitively normal participants from Alzheimer's Disease Neuroimaging Initiative (ADNI) and Open Access Series of Imaging Studies (OASIS), stratified by amyloid status. We evaluated its predictive performance for cognition and diagnostic conversion against cortical thickness, volumetric MRI, and fluid biomarkers.

RESULTS: In both cohorts, brain similarity consistently outperformed other biomarkers across cognitive domains and amyloid groups. It also achieved superior accuracy in predicting clinical conversion and exhibited associations with cytoarchitectural organization.

DISCUSSION: These findings highlight brain similarity as a sensitive marker of early neuroanatomical disruption in AD. Its ability to detect subtle structural changes before overt atrophy underscores its potential for early disease monitoring and treatment assessment in preclinical AD trials.

HIGHLIGHTS: Brain similarity captures early brain changes in preclinical Alzheimer's disease (AD). Brain similarity outperforms conventional biomarkers such as cortical thickness, volume measures, and fluid biomarkers in predicting cognitive decline. Brain similarity predicts conversion to mild cognitive impairment and AD more accurately than traditional imaging markers, and its predictive performance is further improved when combined with fluid biomarkers. Brain similarity captures structural disruptions associated with cortical layer II of the cytoarchitectonic lamina of human neocortex.},
}

Humans
*Alzheimer Disease/diagnostic imaging/pathology
*Magnetic Resonance Imaging
*Cognitive Dysfunction/diagnostic imaging/pathology
Male
Female
*Brain/pathology/diagnostic imaging
Aged
Biomarkers/cerebrospinal fluid
Neuroimaging
Prodromal Symptoms
Aged, 80 and over
Amyloid beta-Peptides/cerebrospinal fluid
Early Diagnosis
Disease Progression

@article {pmid41668114,
year = {2026},
author = {Ng, KP and Chong, JSX and Lussier, F and Therriault, J and Rahmouni, N and Savard, M and Stevenson, J and Pascoal, T and Gauthier, S and Rosa-Neto, P and Zhou, JH},
title = {Functional network phenotypes of mild behavioural impairment: cognitive effects moderated by amyloid.},
journal = {Alzheimer's research & therapy},
volume = {18},
number = {1},
pages = {},
pmid = {41668114},
issn = {1758-9193},
support = {MOP-11-51-31; RFN 152985, 159815, 162303//Weston Brain Institute, Canadian Institutes of Health Research (CIHR)/ ; MOP-11-51-31 -team 1//Canadian Consortium of Neurodegeneration and Aging (CCNA)/ ; NIRG-12-92090, NIRP-12-259245//The Alzheimer's Association/ ; CFI Project 34874; 33397//Brain Canada Foundation/ ; Chercheur Boursier, 2020-VICO-279314//The Fonds de Recherche du Québec - Santé (FRQS)/ ; NMRC/OFLCG19May-0035, NMRC/CIRG/1485/2018, NMRC/CSA-SI/0007/2016, NMRC/MOH-00707-01, NMRC/CG/435 M009/2017-NUH/NUHS, CIRG21nov-0007, HLCA23Feb-0004 and OFIRG24Jul-0049//Singapore National Medical Research Council/ ; RIE2020 AME Programmatic Fund No. A20G8b0102//A*STAR, Singapore/ ; MOE-T2EP40120-0007 and T2EP2-0223-0025, MOE-T2EP20220-0001//Ministry of Education - Singapore/ ; Yong Loo Lin School of Medicine Research Core Funding//National University of Singapore/ ; },
abstract = {BACKGROUND: Mild behavioural impairment (MBI) is a neurobehavioural syndrome that represents an at-risk state for incident cognitive decline. No study to date has systematically investigated whole-brain within- and between- network functional connectivity (FC) disruptions in MBI and their effects on cognitive performance in dementia-free individuals. Hence, we sought to evaluate the whole-brain functional network phenotypes associated with MBI and its subdomains, and their relationships with amyloid and tau pathology in predicting future cognition and function in dementia-free older adults.

METHODS: We studied 203 dementia-free individuals aged between 55 and 90 years (77 males) from the Translational Biomarkers in Aging and Dementia (TRIAD) cohort with baseline functional MRI, amyloid-β [18 F]AZD4694 and tau [18 F]MK6240 PET imaging, and longitudinal neuropsychological assessments up to 32 months. Multivariate associations between MBI-Checklist (MBI-C) subdomain scores and whole-brain FC matrices were examined using partial least squares correlation. We then assessed how these MBI-related network phenotypes were associated with baseline and longitudinal changes in global cognition (via Montreal Cognitive Assessment (MoCA) scores) and functional performance (via clinical dementia rating (CDR) sum of boxes), and whether they interacted with baseline Alzheimer’s disease pathology (global amyloid uptake and tau temporal meta-region-of-interest uptake via PET) to influence future outcomes using linear regression models.

RESULTS: We identified an MBI-related functional network phenotype characterized by greater MBI severity and widespread dysfunctions particularly in higher-order networks. Greater expression of this phenotype was associated with poorer baseline global cognition, as well as greater functional impairment at baseline and over time. Further, baseline global amyloid uptake, but not temporal tau uptake, moderated the effects of baseline MBI-related FC disruptions on longitudinal global cognition changes in dementia-free older adults. Specifically, individuals with higher amyloid burden and greater MBI-related FC disruptions showed accelerated cognitive decline over time. In contrast, the MBI-C total score did not show independent or interactive effects with amyloid and tau burden on longitudinal cognitive and functional outcomes.

CONCLUSIONS: Our findings demonstrated a global MBI-related functional network phenotype in dementia-free individuals that was associated with impaired cognition and function. Moreover, this phenotype interacts with amyloid burden to accelerate cognitive decline, underscoring its relevance in preclinical Alzheimer’s disease.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13195-026-01980-2.},
}

@article {pmid41839479,
year = {2026},
author = {Jiao, Y and Zhang, T and Han, W and Zhang, L and Wang, M and Lyu, Z and Zhao, H and Wang, Z and Zhang, X and Guo, S and Hu, Y and Yang, Y and Fu, P},
title = {Multimodal topographic properties of white matter functional segregation in Alzheimer's disease: A simultaneous PET/MR study.},
journal = {European journal of radiology},
volume = {199},
number = {},
pages = {112782},
doi = {10.1016/j.ejrad.2026.112782},
pmid = {41839479},
issn = {1872-7727},
abstract = {OBJECTIVE: White Matter (WM) functional networks offer insight into the network processes underlying progression along the Alzheimer's disease (AD) continuum. Amyloid (Aβ) retention in WM regions, as measured by Aβ-PET, reflects WM integrity and is associated with cognition. This study used simultaneous PET/MR imaging to investigate topographic alterations in WM functional networks and Aβ-burden networks, aiming to provide objective neuroimaging evidence of white matter-related pathology in Alzheimer's disease.

METHODS: A total of 85 subjects were included in this study, including 42 patients with AD, 24 patients with Prodromal AD (PAD), and 19 age- and sex-matched healthy controls (HC). Cognitive assessments were collected along with clinical information, including the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Every enrolled subject underwent an integrated [18]F-Florbetapir ([18]F-AV45) PET/MR scan. High-resolution T1-weighted structural images, blood oxygen level dependent fMRI (BOLD-fMRI) and diffusion tensor imaging (DTI) data were acquired for all subjects. K-means clustering was utilized to obtain white matter functional networks (BWM) from BOLD-fMRI. Normalized Aβ standardized uptake value ratio (SUVR) was calculated within each BWM, with the whole cerebellum as the reference region. The group covariance matrix was generated by Pearson correlation to construct functional, structural, and Aβ retention networks. Topographic properties including the clustering coefficient, characteristic path length and global efficiency were calculated.

RESULTS: AD patients showed lower mean MMSE and MoCA scores than HC and PAD subjects (pcorrected < 0.001). In the functional network, higher characteristic path length and lower global efficiency were found in AD patients, compared with the PAD and HC groups (both p < 0.05). Higher characteristic path length and lower global efficiency were observed in the Aβ retention network of the AD group (all p < 0.05). Furthermore, the clustering coefficient was lower in AD patients (both p < 0.05). The AD group exhibited a significant difference in functional-Aβ retention coupling compared with the PAD group (p = 0.002) and the HC group (p < 0.001). No significant difference was found in the structural network.

CONCLUSION: We observed cognitive impairment in AD patients as compared with participants of the HC or PAD group. AD patients also showed higher characteristic path length and lower global efficiency in both functional and Aβ retention networks. These results may highlight the importance of the multimodal topographic properties of white matter functional segregation for early diagnosis and personalized management of AD.},
}

@article {pmid41839797,
year = {2026},
author = {Fallone, M and Sivananthan, M and Joseph, M},
title = {Donepezil for Korsakoff Syndrome.},
journal = {American journal of therapeutics},
volume = {},
number = {},
pages = {},
doi = {10.1097/MJT.0000000000002102},
pmid = {41839797},
issn = {1536-3686},
abstract = {BACKGROUND: Korsakoff syndrome is a neurocognitive disorder characterized by memory impairment and confabulation caused by severe or prolonged thiamine deficiency. It is preceded by a type of delirium called Wernickes Encephalopathy, which is reversible. However, once a patient progresses to Korsakoff syndrome, treatment options are limited because there are currently no FDA-approved medications for Korsakoff syndrome. Donepezil is an acetylcholinesterase inhibitor that has shown efficacy in Alzheimer disease and has been theorized to have benefit in other neurologic disorders as well. In this case, we present a patient with Korsakoff syndrome who had improvement in symptoms after starting donepezil.

DATA SOURCE: The information presented here is derived directly from the clinical records and observations of the patient under our care.

FINDINGS AND LIMITATIONS: The case presented here demonstrates improvement in cognition, motivation, and affect in Korsakoff dementia with the use of donepezil. Limitations of this case study and those alike include lack of generalizability, retrospective design, and absence of a control.

CONCLUSIONS: The off-label use of donepezil for Korsakoff syndrome in this case and others has been shown to be beneficial and well tolerated. Ultimately, larger studies are needed to determine safety and efficacy.},
}

@article {pmid41839802,
year = {2026},
author = {Xu, YR and Tao, Y and Lish, AM and Li, S and Ostaszewski, BL and Anderson, AK and Young-Pearse, T and Lawton, TL and Yang, HS and Walsh, DM and Yang, T and Selkoe, DJ},
title = {Novel Monoclonal Antibody Detects Small Aβ Oligomers More Sensitively Than Lecanemab in Alzheimer's Disease CSF, Serum and Culture Media.},
journal = {Annals of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ana.78196},
pmid = {41839802},
issn = {1531-8249},
abstract = {OBJECTIVE: Aqueously diffusible oligomers of the amyloid β-protein (oAβ) are neurotoxic and play a role in neuronal dysfunction in Alzheimer's disease (AD). Accurate quantification of oAβ in brains and biofluids could be valuable for understanding and monitoring AD. In this study, we aimed to examine the ability of 2 antibodies to quantify diffusible oAβ in AD tissue and biofluids.

METHODS: Two oligomer preferring antibodies, 71A1 and lecanemab, were compared to quantify oAβ assemblies in AD brain tissue, cerebrospinal fluid (CSF), serum, and culture media of human neurons expressing Aβ-altering mutations.

RESULTS: Both antibodies recognized synthetic aggregates of Aβ and detected significantly elevated oAβ levels in aqueous extracts of AD versus control brain tissues. Only 71A1 sensitively quantified diffusible oAβ species in CSF, neuronal media, and serum.

INTERPRETATION: Whereas lecanemab is an effective plaque-clearing immunotherapy that robustly detects higher-order Aβ aggregates in AD brain, its preferred Aβ targets are present at very low levels in biofluids. Our results demonstrate that 71A1 detects low-n, diffusible Aβ oligomers that predominate in CSF, serum, and neuronal media that associate with AD-related pathology. Together, these findings indicate that Aβ oligomer populations distribute differently in brain tissue versus biofluids and inform the selection of assays for monitoring oligomers during AD progression and treatment. ANN NEUROL 2026.},
}

@article {pmid41839854,
year = {2026},
author = {Meng, J and Chen, C and Zhu, Z and Sun, Y and Huang, Y and Hu, K and Fu, J and Wu, L and Li, L and Bai, Y and Fei, T and Liu, Z and Li, C and Shen, Z and Liu, L and Li, C and Song, T and Liu, C and Poo, M and Liu, S and Lei, Y and Sun, Y},
title = {Single-cell spatial map of cis-regulatory elements for disease-related genes in the macaque cortex.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-70497-x},
pmid = {41839854},
issn = {2041-1723},
support = {No. T2422026//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
abstract = {Single-cell spatial transcriptomes have demonstrated molecular and cellular diversity in the brain, but gene regulatory mechanisms underlying transcriptomic profiles and disease pathogenesis remain largely unknown in primates. Here we performed single-nucleus Assay for Transposase-Accessible Chromatin followed by sequencing (snATAC-seq) for ~1.6 million cells from 142 cortical regions of two male cynomolgus monkeys (Macaca fascicularis), and identified distinct chromatin accessibility profiles of cis-regulatory elements (CREs) for various cell types. By integrative analysis with large-scale spatial transcriptome data, we found that these CREs showed laminar and regional preferences, with their regional accessibility exhibiting striking dependence on the region's hierarchical level. Cross-species comparison of snATAC-seq data revealed human/macaque-enriched layer-4 glutamatergic neurons and LAMP5/LHX6-expressing GABAergic neurons as well as human/macaque-biased CREs for genes related to neurodevelopment and psychiatric diseases. Importantly, risk single-nucleotide polymorphisms for many brain disorders strongly associated with human/macaque-biased CREs in glutamatergic neuronal types and those for Alzheimer's disease strongly associated with CREs exclusively in microglia. Our results provided the basis for understanding the spatial gene regulatory mechanisms underlying cellular diversity and disease pathogenesis in the primate cortex.},
}

@article {pmid41839929,
year = {2026},
author = {Marschner, RA and Ribeiro, RT and Gayger-Dias, V and Da Silva, VF and Wajner, SM and Gonçalves, CA},
title = {Increased type 3 deiodinase reduces hippocampal T3 signaling and is associated with cognitive impairment in a sporadic Alzheimer's disease animal model.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-43232-1},
pmid = {41839929},
issn = {2045-2322},
support = {171607/2023-6//Conselho Nacional de Desenvolvimento Científico e Tecnológico , Brasil/ ; 302102/2022-1//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; },
}

@article {pmid41840186,
year = {2026},
author = {Düzel, E and Kreutz, MR},
title = {Maintaining and regaining episodic memory in Alzheimer disease: a circuit-based perspective.},
journal = {Nature reviews. Neurology},
volume = {},
number = {},
pages = {},
pmid = {41840186},
issn = {1759-4766},
abstract = {Losing track of personal experiences is a defining feature of Alzheimer disease (AD), arising from the spread of AD pathology through the brain circuits that support episodic memory. In this Review, we explore strategies to improve the function of episodic memory circuits in AD by leveraging the optimized use of neural resources. We introduce the circuit utilization framework, which builds on evidence that synaptic dysfunction, maladaptive responses and deficient adaptive plasticity contribute to episodic memory impairment. The circuit utilization framework posits that by optimizing the utilization of circuit resources, episodic memory function can be partially regained. Our focus includes mitigation of hypoactive and hyperactive synaptic dysfunction, reduction of maladaptive processes and enhancement of brain and cognitive reserve. The circuit utilization framework is grounded in circuit-specific hypotheses that link the component processes of episodic memory to clinical symptoms of memory impairment and AD progression. Its overarching aim is to guide the development of interventions that support episodic memory in people with AD, complementing disease-modifying treatments such as anti-amyloid antibody therapies.},
}

@article {pmid41840280,
year = {2026},
author = {Zuliani, G and Cervellati, C and Zuin, M and Brombo, G},
title = {Why acetylcholinesterase inhibitors should be considered disease-modifying drugs for Alzheimer's disease?.},
journal = {Aging clinical and experimental research},
volume = {},
number = {},
pages = {},
doi = {10.1007/s40520-026-03353-z},
pmid = {41840280},
issn = {1720-8319},
}

@article {pmid41840283,
year = {2026},
author = {Yilmaz, U},
title = {[Magnetic resonance imaging in dementia].},
journal = {Radiologie (Heidelberg, Germany)},
volume = {},
number = {},
pages = {},
pmid = {41840283},
issn = {2731-7056},
abstract = {Magnetic resonance imaging (MRI) plays a pivotal role in the diagnostic work-up of dementia. In addition to excluding secondary and potentially treatable causes, MRI enables the identification of characteristic neuroanatomical patterns that support the differentiation between major dementia entities. In daily clinical practice, the diagnostic value of MRI relies primarily on systematic visual assessment and semiquantitative evaluation of regional atrophy patterns and accompanying vascular pathology. In recent years, automated morphometric analyses and artificial intelligence (AI)-based approaches have gained increasing attention. While these techniques promise objective quantification of structural brain changes, their clinical utility on an individual patient level remains limited. High interindividual variability of brain volumes, technical dependencies, and normative database issues restrict their diagnostic accuracy and may lead to overinterpretation of numerical results if used outside the appropriate context. This review provides a clinically oriented overview of MRI in dementia imaging. Emphasis is placed on pattern-based visual assessment, the role of established semiquantitative rating scales and a critical appraisal of automated morphometry. A practical imaging algorithm is proposed that integrates visual analysis, rating scales and quantitative tools in a structured manner. The aim is to highlight the realistic clinical value of MRI and to emphasize its role as an interpretative rather than a purely numerical diagnostic modality.},
}

@article {pmid41840318,
year = {2026},
author = {Paliwal, S and Bhardwaj, JS and Yang, CH and Taliyan, R},
title = {Unravelling Epigenetic Modulation via MicroRNA Delivery: A Therapeutic Frontier for Alzheimer's.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {41840318},
issn = {1559-1182},
support = {BT/INF/22/SP42545/2021//Department of Biotechnology- BUILDER/ ; },
mesh = {*MicroRNAs/administration & dosage/genetics/metabolism ; *Alzheimer Disease/genetics/therapy ; Humans ; *Epigenesis, Genetic ; Animals ; *Gene Transfer Techniques ; tau Proteins/metabolism ; },
abstract = {Alzheimer's disease (AD) is a common form of dementia that primarily affects the elderly population. Several signalling pathways, including Wnt/β-catenin and PI3K/Akt, are significantly affected, disrupting normal physiological processes such as neurogenesis, neuronal survival, neuroinflammation, and BBB disruption, all of which contribute to the progression of AD-like conditions. The current study seeks to investigate and evaluate the involvement of the PI3K-Akt and Wnt/β-catenin pathways in AD, as well as epigenetic regulators that may alter these pathways and be employed as a treatment to improve AD-like conditions. A class of epigenetic regulators known as miRNAs, or short non-coding RNAs, greatly affects gene expression by preventing translation or encouraging target gene destruction. This review will focus on how miRNAs affect Aβ peptide accumulation, hyperphosphorylated tau protein aggregation, and neuroinflammation. In addition, miRNA delivery through exosomes, a lipid nanoparticle, has also been explored in later sections. Our knowledge will assist in creating new miRNA-based therapeutics involving mimics/inhibitors and advance our understanding of how miRNAs control gene expression.},
}

*MicroRNAs/administration & dosage/genetics/metabolism
*Alzheimer Disease/genetics/therapy
Humans
*Epigenesis, Genetic
Animals
*Gene Transfer Techniques
tau Proteins/metabolism

@article {pmid41840320,
year = {2026},
author = {Rai, PK and Srivastava, V},
title = {Claustrum and Hippocampus Segmentation-Based Alzheimer's Disease Identification Model Using RoT-Kmeans and CoLU-CNN.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {41840320},
issn = {1559-1182},
mesh = {*Alzheimer Disease/diagnostic imaging ; *Hippocampus/diagnostic imaging/pathology ; Humans ; Magnetic Resonance Imaging/methods ; *Claustrum/diagnostic imaging/pathology ; *Neural Networks, Computer ; Male ; Gray Matter ; Image Processing, Computer-Assisted/methods ; },
abstract = {Alzheimer's disease (AD) is a dementia disease that causes loss of cognitive functions. Also, it is a noncurable disease. However, early diagnosis and proper medication reduce AD's progression time. Yet, the prevailing AD diagnosis models did not concentrate on the claustrum in the brain, reducing the efficiency of the AD diagnosis. Thus, this framework proposes an effective AD identification model with claustrum segmentation based on Collapsing Linear Unit-Convolutional Neural Network (CoLU-CNN). Primarily, the resting state-functional Magnetic Resonance Imaging (rs-fMRI) is preprocessed. Then, Gray Matter (GM), White Matter (WM), Cerebrospinal Fluid (CSF), and the hippocampus are segmented. By using Rogers and Tanimoto-based K-means (RoT-Kmeans), the putamen edge is detected from the segmented GM to segment the claustrum. Likewise, the time-series extraction is performed from rs-fMRI, and network connectivity is generated by using Seed-Based Functional Connectivity (SBFC). Then, the network connectivity and segmented claustrum are mapped. Next, the features are extracted from the segmented and mapped images, and optimal features are selected by using Kent Map-based Wild Geese Optimization (KM-WGO). Lastly, the AD is classified by using CoLU-CNN. The experimental investigation stated that the proposed methodology attained 99% AD classification accuracy.},
}

*Alzheimer Disease/diagnostic imaging
*Hippocampus/diagnostic imaging/pathology
Humans
Magnetic Resonance Imaging/methods
*Claustrum/diagnostic imaging/pathology
*Neural Networks, Computer
Male
Gray Matter
Image Processing, Computer-Assisted/methods

@article {pmid41840370,
year = {2026},
author = {Gönüllü, S and Aydın, Ş and Çelik, H and Çelik, O and Küçükler, S and Topal, A and Akay, R and Yıldız, MO and Alım, B and Özdemir, S},
title = {Milk-derived miR-126-3p-loaded small extracellular vesicles attenuate amyloid-β-induced cellular stress in a neuroblastoma cell model.},
journal = {BMC neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12868-026-01002-9},
pmid = {41840370},
issn = {1471-2202},
}

@article {pmid41840418,
year = {2026},
author = {Burns, LH and Romero, A},
title = {Filamin A phosphorylation at S2152: A molecular switch fueling cancer and neurodegeneration.},
journal = {Cell communication and signaling : CCS},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12964-026-02806-2},
pmid = {41840418},
issn = {1478-811X},
}

@article {pmid41840770,
year = {2026},
author = {Clouston, SAP and Hanes, DW and Smith, DM},
title = {An exploration of sources of bias in population models of cognitive aging and accelerated decline: A prospective cohort study.},
journal = {The journals of gerontology. Series B, Psychological sciences and social sciences},
volume = {},
number = {},
pages = {},
doi = {10.1093/geronb/gbag040},
pmid = {41840770},
issn = {1758-5368},
abstract = {OBJECTIVES: Epidemiologic models used to model cognitive aging and decline often rely on a linear random slopes model, though clinicians rely on accelerated cognitive decline for diagnosis. This study examined the extent to which accelerated versus linearized models of cognitive decline are biased by study design and analytic choices.

METHODS: Data on participants of the Health and Retirement Study (1998-2019) who completed cognitive monitoring and lacked cognitive functional limitations or a history of stroke at baseline were included. Episodic memory was measured as the outcome at each time-point. Experiments manipulated sample size, gaps between observations, and waves/participants, and the degree of censoring due to factors in the model, and the degree of cognitive functional limitations. The outcome was the degree of bias in rates of cognitive decline estimated by different models when compared with the full sample.

RESULTS: This study used data from 30,740 HRS participants followed 194,818 times and for 335,025.73 person-years of cognitive assessment. While linear models were often biased by relatively small changes in sample design, attrition, and analytic choices, quadratic models and nested nonlinear models provided results that were less biased. Nested nonlinear models were less biased than linear models across 4/5 experimental conditions and were less biased than quadratic models in 3/5 experimental conditions.

DISCUSSION: Linearized models of cognitive decline yielded high levels of bias that were sensitive to variations in study design and analytic choices. Results support shifting towards methods modeling accelerated decline in studies of cognitive aging and decline.},
}

@article {pmid41840857,
year = {2026},
author = {Biju, AP and Karim, F and Schafer, DM and Sison, SA and Liang, C and Head, E and Mukherjee, J},
title = {Measurement of Tau Protein and Aβ Amyloid Plaques in Postmortem Human Brains of Down Syndrome and Alzheimer's Disease by Using [[125]I]IPPI and [[125]I]IBETA Autoradiography.},
journal = {Synapse (New York, N.Y.)},
volume = {80},
number = {2},
pages = {e70044},
doi = {10.1002/syn.70044},
pmid = {41840857},
issn = {1098-2396},
support = {AG 077700/NH/NIH HHS/United States ; },
mesh = {Humans ; *tau Proteins/metabolism ; *Alzheimer Disease/metabolism/pathology/diagnostic imaging ; *Down Syndrome/metabolism/pathology/diagnostic imaging ; Autoradiography/methods ; Male ; Female ; Middle Aged ; *Plaque, Amyloid/metabolism/pathology/diagnostic imaging ; Iodine Radioisotopes ; Aged ; *Amyloid beta-Peptides/metabolism ; *Brain/metabolism/pathology/diagnostic imaging ; Aged, 80 and over ; },
abstract = {The accumulation of tau tangles and Aβ plaques are prominent neuropathologies that characterize Alzheimer's disease (AD) and Down syndrome (DS). Continuous developments of PET tracers as biomarkers can be supported by autoradiography to validate effectiveness and accuracy of binding properties that elucidate the pathophysiology of DSAD and AD. This in vitro comparative study evaluates [[125]I]IPPI binding to tau and [[125]I]IBETA binding to Aβ plaques in the frontal cortex (FCX) and temporal cortex (TCX) of postmortem human brain slices of AD (n = 5), DSAD (n = 5), and cognitively normal (CN) (n = 5) cases. With anti-tau and anti-Aβ immunostains confirming the presence of tau and Aβ plaques, [[125]I]IPPI and [[125]I]IBETA binding in autoradiographic images were significantly higher in DSAD and AD gray matter (GM) compared to CN. When comparing DSAD with AD, FCX and TCX GM binding was similar throughout DSAD and AD, except in FCX GM where there was 48% more [[125]I]IPPI binding in DSAD than AD. In vitro drug inhibition studies revealed that [[125]I]IPPI binding was significantly inhibited with increasing harmine concentrations (IC50 = 115 nM) in DSAD FCX and TCX, but KuFal194, a DYRK1A drug, minimally inhibited [[125]I]IPPI binding in the same cases. The GM/white matter ratios for DSAD ([[125]I]IPPI = 4.1, [[125]I]IBETA = 2.9) and AD ([[125]I]IPPI = 4.2, [[125]I]IBETA = 2.6) were significantly greater than CN ([[125]I]IPPI = 1.3, [[125]I]IBETA = 1.2). A positive correlation between [[125]I]IPPI and [[125]I]IBETA binding suggests a synergistic relationship between tau and Aβ plaque in DSAD and AD pathology. This study demonstrates that [[125]I]IPPI and [[125]I]IBETA may serve as novel radiotracers in both DSAD and AD to continue diagnostic investigations.},
}

Humans
*tau Proteins/metabolism
*Alzheimer Disease/metabolism/pathology/diagnostic imaging
*Down Syndrome/metabolism/pathology/diagnostic imaging
Autoradiography/methods
Male
Female
Middle Aged
*Plaque, Amyloid/metabolism/pathology/diagnostic imaging
Iodine Radioisotopes
Aged
*Amyloid beta-Peptides/metabolism
*Brain/metabolism/pathology/diagnostic imaging
Aged, 80 and over

@article {pmid41841008,
year = {2026},
author = {Peng, T and Zhang, Z and Ding, N and Zhang, J},
title = {Mechanistic Investigation of Exercise Interventions in Rodent Models of Alzheimer's Disease and Prospects for Clinical Translation.},
journal = {Neural plasticity},
volume = {2026},
number = {1},
pages = {e6718671},
doi = {10.1155/np/6718671},
pmid = {41841008},
issn = {1687-5443},
support = {2025023//Fundamental Research Funds for the Central Universities/ ; },
mesh = {*Alzheimer Disease/therapy/physiopathology/metabolism ; Animals ; Disease Models, Animal ; Gastrointestinal Microbiome/physiology ; *Physical Conditioning, Animal/physiology ; *Exercise Therapy/methods ; Humans ; Translational Research, Biomedical ; Mice ; Brain/metabolism ; Mice, Transgenic ; Neuronal Plasticity/physiology ; },
abstract = {Alzheimer's disease (AD) is a progressive and debilitating neurodegenerative disorder for which existing pharmacotherapies are inadequate to arrest pathological progression, highlighting the imperative to identify safe and effective nonpharmacological interventions. Exercise, as a multi-target therapeutic modality, has been shown to reverse multiple facets of AD-related neuropathology through diverse mechanisms. In this systematic review, we synthesize evidence on the effects of voluntary running, structured swimming, and modulation of the gut microbiota in transgenic murine models of AD. Exercise was found to ameliorate AD pathology by modulating amyloid precursor protein (APP) processing and β-amyloid (Aβ) production/clearance, restoring mitochondrial integrity and function, attenuating neuroinflammatory responses, enhancing synaptic plasticity, and upregulating neurotrophic factors. Moreover, exercise reshapes the intestinal microbiome and thereby modulates the gut-brain axis, further promoting neuroimmune homeostasis and cognitive resilience. Through RNA sequencing data analysis, key genes such as Tlr4, Cdc42, and F13a1 were identified, which may play significant roles in neuroimmune regulation and cognitive protection. By integrating multi-omics evidence, we propose a coordinated "exercise-microbiota-brain" mechanistic framework that offers theoretical support for personalized, exercise-based therapeutic strategies and translational applications in AD. We also emphasize the necessity of future studies combining exercise with complementary interventions to accelerate the clinical translation of multimodal therapeutic approaches.},
}

*Alzheimer Disease/therapy/physiopathology/metabolism
Animals
Disease Models, Animal
Gastrointestinal Microbiome/physiology
*Physical Conditioning, Animal/physiology
*Exercise Therapy/methods
Humans
Translational Research, Biomedical
Mice
Brain/metabolism
Mice, Transgenic
Neuronal Plasticity/physiology

@article {pmid41841031,
year = {2026},
author = {Peng, W and Xia, T and De Sousa Ribeiro, F and Bosschieter, T and Adeli, E and Zhao, Q and Glocker, B and Pohl, KM},
title = {Latent Causal Modeling for 3D Brain MRI Counterfactuals.},
journal = {Deep generative models : 5th MICCAI workshop, DGM4MICCAI 2025, held in conjunction with MICCAI 2025, Daejeon, South Korea, September 23, 2025, Proceedings. DGM4MICCAI (Workshop) (5th : 2025 : Taejon-si, Korea)},
volume = {16128},
number = {},
pages = {192-201},
pmid = {41841031},
abstract = {The number of samples in structural brain MRI studies is often too small to properly train deep learning models. Generative models show promise in addressing this issue by effectively learning the data distribution and generating high-fidelity MRI. However, they struggle to produce diverse, high-quality data outside the distribution defined by the training data. One way to address the issue is using causal models developed for 3D volume counterfactuals. However, accurately modeling causality in high-dimensional spaces is a challenge so that these models generally generate 3D brain MRIS of lower quality. To address these challenges, we propose a two-stage method that constructs a Structural Causal Model (SCM) within the latent space. In the first stage, we employ a VQ-VAE to learn a compact embedding of the MRI volume. Subsequently, we integrate our causal model into this latent space and execute a three-step counterfactual procedure using a closed-form Generalized Linear Model (GLM). Our experiments conducted on real-world high-resolution MRI data (1mm) provided by the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) demonstrate that our method can generate high-quality 3D MRI counterfactuals.},
}

@article {pmid41841751,
year = {2026},
author = {Guo, HH and Ou, HN and Yu, JS and Luo, ZR and Yau, SY and Tsang, HW},
title = {The Adiponectin-PP2A Pathway Confers Cognitive Benefits of Physical Exercise Against Chronic Stress-Induced Tau Hyperphosphorylation in the Hippocampus.},
journal = {Aging cell},
volume = {25},
number = {3},
pages = {e70447},
doi = {10.1111/acel.70447},
pmid = {41841751},
issn = {1474-9726},
support = {82072529//National Natural Science Foundation of China/ ; 2021KSYS009//Key Laboratory of Guangdong Higher Education Institutes/ ; 2022M720907//China Postdoctoral Science Foundation/ ; //Mental Health Research Center (MHRC) at Hong Kong Polytechnic University./ ; },
mesh = {Animals ; *Hippocampus/metabolism ; *tau Proteins/metabolism ; *Adiponectin/metabolism/genetics ; Mice ; *Physical Conditioning, Animal ; Phosphorylation ; *Cognition/physiology ; *Protein Phosphatase 2/metabolism/genetics ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; },
abstract = {Protein phosphatase 2A (PP2A) regulates Tau hyperphosphorylation in Alzheimer's disease (AD). This study hypothesized that exercise increases adiponectin levels, activating PP2A to reduce Tau hyperphosphorylation and enhance hippocampal plasticity. The study utilized adiponectin knockout (Adipo[-/-]) and hippocampal-specific PP2A knockdown (PP2A-KD) in mice with 3-week voluntary running and/or chronic stress to assess changes in Tau phosphorylation, adult neurogenesis, and cognitive performance. Running improved cognitive deficits and reduced Tau hyperphosphorylation in association with increased adiponectin levels and enhanced PP2A activity in stressed mice. Adiponectin deficiency impaired cognitive performance, increased Tau phosphorylation, and decreased PP2A activity. Mechanistically, adiponectin is dispensable for running to increase PP2A activity, reduce Tau hyperphosphorylation, and restore hippocampal neurogenesis, leading to cognitive improvement. Hippocampal-specific PP2A knockdown diminished the beneficial effects of running, indicating that PP2A is downstream of adiponectin's action. This study provides mechanistic insights into how exercise reduces AD-like neuropathology, emphasizing the critical role of the adiponectin-PP2A pathway in mitigating Tau hyperphosphorylation and suggesting a potential therapeutic target for AD through modulation of this pathway.},
}

Animals
*Hippocampus/metabolism
*tau Proteins/metabolism
*Adiponectin/metabolism/genetics
Mice
*Physical Conditioning, Animal
Phosphorylation
*Cognition/physiology
*Protein Phosphatase 2/metabolism/genetics
Male
Mice, Inbred C57BL
Mice, Knockout

@article {pmid41842176,
year = {2025},
author = {Zhang, Z and Huang, X and Wang, Y and Cao, Y and Wang, W and Huang, L and Shu, G and Liu, G},
title = {Loss-amplification-radiation coupling model of the mid-infrared signal propagating in demyelinated axons.},
journal = {Applied optics},
volume = {64},
number = {34},
pages = {10380-10387},
doi = {10.1364/AO.574928},
pmid = {41842176},
issn = {1539-4522},
mesh = {*Axons/physiology/pathology ; *Demyelinating Diseases/physiopathology ; *Infrared Rays ; Humans ; Myelin Sheath ; Computer Simulation ; *Models, Neurological ; },
abstract = {Many neurological disorders are associated with demyelination, leading to abnormalities in neural signal transmission. This study presents a loss-amplification-radiation coupling model for the transmission mechanisms of terahertz and infrared signals in demyelinated axons with disruption and rupture. Demyelinated axons are treated as dielectric antennas, and the radiation characteristics at different degrees of demyelination are investigated through simulations in the frequency range of 55-75 THz. The results indicate that radial demyelination tends to increase radiation more significantly than axial demyelination. The directivity and radiation efficiency reach 18.76 dBi and -1.17dB for severe demyelination (Ld/L>0.5 and td/t>0.5), respectively. Ruptured myelin axons can maintain signal transmission within a certain distance of less than 15 µm in the simulation. These results are consistent with previous studies and may enhance the understanding of mid-infrared signal propagation mechanisms in nerves, as well as contribute to research on diseases associated with demyelination, such as multiple sclerosis and Alzheimer's disease.},
}

*Axons/physiology/pathology
*Demyelinating Diseases/physiopathology
*Infrared Rays
Humans
Myelin Sheath
Computer Simulation
*Models, Neurological

@article {pmid41842662,
year = {2026},
author = {Sun, Y and Ji, M and Leng, M and Wang, Z},
title = {Effects and mechanisms of a mobile-based intelligent recommender system for dementia care on the psychological health of family caregivers: A secondary analysis of a randomized clinical trial.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261427705},
doi = {10.1177/13872877261427705},
pmid = {41842662},
issn = {1875-8908},
abstract = {BackgroundHealth recommender systems show promise in delivering remote support and improving coping among family caregivers of persons with dementia.ObjectiveTo evaluate the effectiveness of a mobile-based intelligent recommender system for dementia care (DCIRS) in enhancing psychological well-being among family caregivers and to explore the mechanisms underlying its effects.MethodsData from a randomized controlled trial (RCT) were used. Of the 250 eligible participants, 125 caregivers were randomly allocated to the intervention group (receiving DCIRS) and 125 to the waitlist control group. Outcomes, including benefit finding, depressive symptoms, self-efficacy, and coping styles, were assessed at baseline (T0), 6 weeks (T1), and 12 weeks (T2). Generalized estimating equations (GEE) was used to evaluate changes over time and between-group differences, while path analysis examined mediation pathways.ResultsAt 12 weeks, the intervention group showed significant within-group improvements in coping, self-efficacy, and benefit finding (all p < 0.05 for group × time interaction). Between-group analyses revealed greater reductions in depressive symptoms at T1 and T2, though the group × time interaction was non-significant (p = 0.393). Path analysis indicated that reduced depressive symptoms were mediated primarily by increased self-efficacy.ConclusionsThis DCIRS demonstrated the potential to reduce depressive symptoms and enhance benefit finding in caregivers of people with dementia. Strengthening self-efficacy and active coping styles should remain a core focus in digital health interventions, providing meaningful guidance to healthcare professionals in developing caregiver support program.},
}

@article {pmid41842683,
year = {2026},
author = {Lipnicki, DM and Vella, AS and Castro-Costa, E and Blay, SL and Lima-Costa, MF and Ritchie, K and Rolandi, E and Davin, A and Rossi, M and Kim, KW and Han, JW and Oh, DJ and Ding, D and Zhao, Q and Zhou, X and Chen, YC and Chen, JH and Sachdev, PS and , },
title = {Disturbing dreams and dementia incidence across diverse cohort studies: A COSMIC collaboration study.},
journal = {Psychiatry and clinical neurosciences},
volume = {},
number = {},
pages = {},
doi = {10.1111/pcn.70046},
pmid = {41842683},
issn = {1440-1819},
support = {104-2314-B-002-038-MY3//National Science and Technology Council/ ; 107-2314-B-002-186-MY3//National Science and Technology Council/ ; 107-2314-B-002-230//National Science and Technology Council/ ; 108-2314-B-002-128-MY2//National Science and Technology Council/ ; 110-2314-B-002-068//National Science and Technology Council/ ; 110-2314-B-002-129-MY3//National Science and Technology Council/ ; R01AG057531/AG/NIA NIH HHS/United States ; APP1196150//National Health and Medical Research Council/ ; },
abstract = {AIM: Distressing dreams were previously reported to predict future all-cause dementia among predominantly white US participants aged 79-89 years, particularly in men. We investigated whether disturbing dreams (nightmares and bad dreams) were associated with all-cause and Alzheimer dementia (AD) among individuals aged 60-89 years from diverse international regions.

METHODS: Data were from six longitudinal cohort studies across Brazil, China, France, Italy, South Korea, and Taiwan (n = 10,238, 42.5% men). Cox regressions with a random effect for study investigated associations between disturbing dreams and incident dementia, with all participants and stratified separately by sex and baseline age. Analyses examined (i) any disturbing dreams and (ii) disturbing dreams at least once a week. Fully adjusted analyses included three studies with covariates for sleep problems, medications, mental and physical health, cognition, and APOE ε4 status.

RESULTS: Disturbing dreams were reported by 24.2% overall and all-cause dementia, and AD incidence was 10.8 and 5.3 per 1000 person-years, respectively. In fully adjusted analyses, having any disturbing dreams was associated with increased incidence of all-cause dementia among 60-69-year-olds (hazard ratio [HR] 3.93, 95% confidence interval [CI] 1.32-11.67). There were no significant effects for older individuals. In fully adjusted sex-stratified analyses, having disturbing dreams at least once a week was associated with AD only among men (HR 3.59, 95% CI 1.44-8.96).

CONCLUSIONS: We found some evidence for disturbing dreams being associated with incident all-cause dementia among individuals aged 60-69 years and with AD among men. The mechanisms potentially underlying these associations remain to be clarified.},
}

@article {pmid41842757,
year = {2026},
author = {Agnello, L and Dukic, L and Akvlediani, L and Zaninotto, M and , },
title = {Current practices and harmonization challenges in Alzheimer's disease biomarkers: an EFLM Committee: Harmonization Survey.},
journal = {Clinical chemistry and laboratory medicine},
volume = {},
number = {},
pages = {},
pmid = {41842757},
issn = {1437-4331},
abstract = {OBJECTIVES: Fluid biomarkers are central to the biological definition and diagnosis of Alzheimer's disease (AD). Despite international recommendations, substantial variability persists in laboratory practices. This survey, promoted by the Committee: Harmonisation (C:H) of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM), aimed to assess real-world laboratory practices for AD biomarker testing.

METHODS: An online survey was distributed to EFLM members. The questionnaire addressed pre-analytical, analytical, and post-analytical practices for cerebrospinal fluid (CSF) and blood-based AD biomarkers. Descriptive statistics were applied.

RESULTS: A total of 316 responses from more than 35 countries were collected. CSF remained the primary matrix for AD diagnostics, although blood-based biomarkers were increasingly implemented. Marked heterogeneity was observed across all phases of testing, including sample handling, assay platforms, biomarker panels, and decisional cut-offs. Cut-off values for core biomarkers varied widely, as well as harmonization of reporting unit and the adoption of SI units preventing a shared approach to interpreting the results.

CONCLUSIONS: Despite growing clinical adoption, AD biomarker testing remains highly heterogeneous. Coordinated international harmonization of pre-analytical procedures, analytical methods, and post-analytical interpretation, particularly for blood-based biomarkers, is urgently required to ensure reliable and comparable results.},
}

@article {pmid41842840,
year = {2026},
author = {Kortmann, E and Steinacker, P and Guthknecht, A and Weise, CM and Otto, M},
title = {Serum as an alternative to plasma for determining the ApoE4 phenotype using Pan-ApoE and ApoE4 chemiluminescent enzyme immunoassays.},
journal = {Clinical chemistry and laboratory medicine},
volume = {},
number = {},
pages = {},
pmid = {41842840},
issn = {1437-4331},
abstract = {OBJECTIVES: Since apolipoprotein E4 (ApoE4) is associated with therapy-related adverse effects of anti-amyloid-β monoclonal antibodies in Alzheimer's disease, such as amyloid-related imaging abnormalities, methods for determining the ApoE4 status are needed. The Lumipulse[®] ApoE4 and Pan-ApoE assays provide a practical approach, but they have so far been validated only in plasma.

METHODS: Plasma and serum obtained from a single blood draw from 157 patients were analyzed using ApoE4 and Pan-ApoE chemiluminescent enzyme immunoassays. The APOE genotype was determined by allele-specific quantitative polymerase chain reaction. Additional experiments assessed assay repeatability, intermediate precision, and sample stability under various storage conditions.

RESULTS: ApoE4, Pan-ApoE, and the resulting ApoE4/Pan-ApoE ratio showed minimal bias, strong positive correlation and linearity between plasma and serum. Using matrix-specific thresholds, plasma- and serum-derived ApoE4/Pan-ApoE ratios accurately classified the ApoE4 phenotypes in concordance with APOE ε4 genotypes. The assay demonstrated repeatability of <15 % and <5 % (day 1 and 2), with intermediate precision <10 % for both Pan-ApoE and ApoE4. Plasma and serum showed both comparable stability after multiple freeze-thaw-cycles and up to 120 h at 4 °C, while serum showed deterioration after 120 h storage at 20 °C.

CONCLUSIONS: Using matrix-specific thresholds, the ApoE4/Pan-ApoE ratio in plasma and serum accurately classified the ApoE4 phenotype in concordance with APOE ε4 genotypes. Serum and plasma showed comparable stability and precision. Thus, serum is a reliable alternative to plasma for measuring Pan-ApoE and ApoE4 with the Lumipulse assays. The use of serum expands sample availability, particularly in retrospective studies or when collected alongside cerebrospinal fluid.},
}

@article {pmid41843337,
year = {2026},
author = {Roy, KK and Mehta, DK and Das, R},
title = {Unrevealing possible mechanism of Riluzole, Salsalate and Nimodipine in Alzheimer's disease: multi-target network pharmacological perspective.},
journal = {Inflammopharmacology},
volume = {},
number = {},
pages = {},
pmid = {41843337},
issn = {1568-5608},
}

@article {pmid41843546,
year = {2026},
author = {Stingl, J and Guyette, FX and Drábek, T},
title = {Accidental Environmental Hypothermia in a Nonagenarian Resulting in Cardiac Arrest.},
journal = {Prague medical report},
volume = {127},
number = {1},
pages = {39-43},
doi = {10.14712/23362936.2026.6},
pmid = {41843546},
issn = {1214-6994},
mesh = {Humans ; Female ; *Heart Arrest/etiology/therapy ; *Hypothermia/complications/therapy ; Aged, 80 and over ; },
abstract = {Accidental hypothermia after environmental exposure and/or impaired thermoregulation resulting in significant decrease in body temperature and cardiac arrest (CA) is linked to 1,500 deaths annually in the United States. Hypothermic CA treatment has specific presentation and clinical features. With appropriate treatment, its survival can reach 27-70%, contrasting ~ 10% in medical CA. Majority of accidental hypothermic CA survivors recover with favourable neurologic outcome. An integrated, dedicated multi-disciplinary team-approach is essential to maximize the chances of survival. We report on a 91-year-old female who was found outside and unresponsive in freezing temperatures. During transport, she required bag-and-mask ventilation. An esophageal temperature recorded 24.5 °C. Shortly after rapid sequence intubation, she developed CA. She was successfully resuscitated with chest compressions, epinephrine, atropine, and two defibrillations. Due to persistent hypothermia and bradycardia, she was rewarmed using extracorporeal membrane oxygenation. Perioperative transesophageal echocardiography showed normal cardiac function. She was extubated the next day. She remained stable for the rest of her hospital stay without focal neurological deficits on serial examinations. However, her post-arrest stay was complicated by acute delirium, likely from underlying dementia, with a waxing and waning level of consciousness, confusion, agitation and hallucinations. She was discharged on post-operative day 5. Her long-term recovery was complicated by repeated aspiration pneumonias, and gradual decline of her mental status due to Alzheimer's dementia. She died approximately two years later at the age of 93. Thus, full neurologic recovery remains possible after CA induced by severe hypothermia from environmental exposure, despite extreme age and frailty.},
}

Humans
Female
*Heart Arrest/etiology/therapy
*Hypothermia/complications/therapy
Aged, 80 and over

@article {pmid41843743,
year = {2026},
author = {Madeline, V and Galvin, A and De Graaf, L and Engelhardt, J and Lebailly, P and Baldi, I},
title = {Farming exposures and Alzheimer's disease: cross-sectional analysis within the French AGRICAN cohort.},
journal = {Scandinavian journal of work, environment & health},
volume = {},
number = {},
pages = {},
doi = {10.5271/sjweh.4284},
pmid = {41843743},
issn = {1795-990X},
abstract = {OBJECTIVE: There is epidemiological evidence of an association between occupational pesticide exposure and cognitive impairment, but studies on the link with Alzheimer`s disease are scarce. We explored the association between agricultural exposures and Alzheimer`s disease in the AGRICAN cohort.

METHODS: We analyzed the relationship between doctor-diagnosed Alzheimer`s disease and life-long exposures separately among men and women with the following exposures: work on a farm, pesticide use in any job, growing specific crops (N=13) or rearing animals (N=5), pesticide use on these crops/livestock, with adjustment for age, education, smoking, alcohol consumption and body mass index.

RESULTS: Among 109 287 participants in the analysis, 818 (267 men, 551 women) were classified as Alzheimer`s disease cases. Increased risks were seen for work on a farm [men: odds ratio (OR) 1.81, 95% confidence interval (CI) 0.92-3.57; women: OR 1.58, 95% CI 0.94-2.86] or pesticide use in any job (men: OR 1.14, 95% CI 0.85-1.53; women: OR 1.42, 95% CI 1.10-1.85). Risks for crops and livestock were close to unity when compared with non-farmers, except for pigs (OR 1.38, 95% CI 1.01-1.89) and rapeseed among men (OR 1.45, 95% CI 1.00-2.11) and sunflower among women (OR 1.55, 95% CI 0.90-2.66). Using pesticides increased the risk among men especially for sheep/goats (OR 1.98, 95% CI 1.18-3.34), pigs (OR 1.80, 95% CI 1.19-2.74), potatoes (OR 1.47, 95% CI 1.03-2.10) and meadows (OR 1.54, 95% CI 1.14-2.08). Among women, risks associated with pesticide use on crops were generally elevated, reaching a two-fold increase for corn, rapeseed, sunflower, field peas and fruit growing.

CONCLUSION: Our results suggest that agricultural exposures may play a role in Alzheimer's disease among both men and women, with the highest risks associated with pesticide use in certain livestock and crop activities.},
}

@article {pmid41843801,
year = {2026},
author = {Ostenso, S and Birkeland, RW and Albers, E and Louwagie, KW and Iwan, A and Chesak, SS and Gaugler, JE},
title = {The TBI-AD/ADRD Caregiver Support Intervention (TACSI): Protocol of a Pilot Randomized Controlled Trial Evaluation of a Remote Intervention for Family Caregivers.},
journal = {JMIR research protocols},
volume = {15},
number = {},
pages = {e81125},
doi = {10.2196/81125},
pmid = {41843801},
issn = {1929-0748},
mesh = {Humans ; *Caregivers/psychology/education ; Pilot Projects ; *Brain Injuries, Traumatic/psychology/therapy ; *Alzheimer Disease/therapy/psychology ; Male ; Female ; Social Support ; Middle Aged ; Adult ; },
abstract = {BACKGROUND: Across the United States, there are millions of informal (ie, unpaid) caregivers helping individuals with Alzheimer Disease/Alzheimer Disease and Related Dementias (AD/ADRD), traumatic brain injury (TBI), or both. TBI is a risk factor for developing, and often co-occurs with, AD/ADRD. In the next decade, more informal caregivers will have to navigate the complexities of the dual diagnosis of TBI and AD/ADRD. Currently, there is a paucity of interventions for caregivers dealing with this dual diagnosis. Our team designed the TBI-AD/ADRD caregiver support intervention (TACSI) as a support program to meet the needs of those providing care to individuals with dual diagnoses of TBI and AD/ADRD.

OBJECTIVE: This pilot randomized controlled trial (RCT) evaluates the preliminary efficacy and successful implementation of TACSI, a 6-session semistructured psychosocial and psychoeducational program, over a 6-month period.

METHODS: This pilot RCT uses an embedded mixed methods randomized controlled evaluation. Caregivers of individuals with a dual diagnosis of AD/ADRD and a history of TBI are randomly assigned to the TACSI (n=41) or a usual care control condition (n=39). Primary outcomes include perceived burden, caregiver relationship satisfaction, and caregiving mastery. Secondary outcomes include caregiver self-efficacy, well-being, and personal resources. Qualitative elements (up to 20 semistructured interviews at the conclusion of the 6-month evaluation and an open-response item at follow-up surveys) allow for better interpretation of quantitative results and understanding of TACSI's mechanisms of benefit.

RESULTS: Recruitment for the study was completed in October 2024. Survey collection and intervention were completed in June 2025. Data analysis will follow.

CONCLUSIONS: Having a dual diagnosis of AD/ADRD and a history of TBI is relatively common. However, there are currently no caregiver support interventions specific to this dual diagnosis. It is important to support these caregivers as they encounter the unique challenges of managing TBI and AD/ADRD. This pilot RCT will help determine if the TACSI program can help to increase caregiving skills and strategies and provide support to improve mood and reduce stress for caregivers of individuals with AD/ADRD and a history of TBI, and also determine if it is feasible to proceed to a full-scale RCT.},
}

Humans
*Caregivers/psychology/education
Pilot Projects
*Brain Injuries, Traumatic/psychology/therapy
*Alzheimer Disease/therapy/psychology
Male
Female
Social Support
Middle Aged
Adult

@article {pmid41843841,
year = {2026},
author = {Zagryadskaya, YA and Nesterov, SV and Mitkevich, VA and Kozin, SA and Kryuchkova, AK and Lomakina, GY and Karbyshev, MS and Bocharov, EV and Makarov, AA and Okhrimenko, IS},
title = {Beta-Amyloid Suppresses Mitochondrial ATP Production in Human Neuroblastoma Cells.},
journal = {Biochemistry. Biokhimiia},
volume = {91},
number = {2},
pages = {230-244},
doi = {10.1134/S0006297925602060},
pmid = {41843841},
issn = {1608-3040},
mesh = {Humans ; *Amyloid beta-Peptides/pharmacology/metabolism ; *Mitochondria/metabolism/drug effects ; *Adenosine Triphosphate/biosynthesis/metabolism ; *Neuroblastoma/metabolism/pathology ; Cell Line, Tumor ; Alzheimer Disease/metabolism ; },
abstract = {β-Amyloid peptides (Aβ), which play a crucial role in the pathogenesis of Alzheimer's disease by forming toxic oligomeric species, are known to affect mitochondrial function. In this study, luciferin-luciferase assay was used to assess changes in ATP production by mitochondria isolated from human neuroblastoma SH-SY5Y cells cultured in the presence of monomeric Aβ at a nanomolar concentration. ATP synthesis rates were measured in the presence of substrates specific for respiratory chain complexes I, II, and IV alongside inhibitors targeting the other complexes. Aβ significantly reduced both the rate of ATP generation and amount of ATP synthesized by mitochondria. This effect of Aβ on ATP synthesis did not result from a direct influence on the respiratory chain complexes I, II, and IV. Our findings provide insights into possible causes of mitochondrial dysfunction in neurons in Alzheimer's disease.},
}

Humans
*Amyloid beta-Peptides/pharmacology/metabolism
*Mitochondria/metabolism/drug effects
*Adenosine Triphosphate/biosynthesis/metabolism
*Neuroblastoma/metabolism/pathology
Cell Line, Tumor
Alzheimer Disease/metabolism

@article {pmid41843859,
year = {2026},
author = {Knopman, DS and Pike, JR and Griswold, M and Lu, Y and Gross, A and Mosley, TH and Windham, BG and Albert, MS and Walker, KA and Gottesman, RF and Sullivan, KJ and Yasar, S and Coresh, J and Burgard, S and Palta, P},
title = {Contingency of Plasma Dementia Biomarkers on Cognitive Profiles for Prognosis of Incident Dementia: The ARIC Study.},
journal = {Neurology},
volume = {106},
number = {7},
pages = {e214779},
doi = {10.1212/WNL.0000000000214779},
pmid = {41843859},
issn = {1526-632X},
mesh = {Humans ; Female ; Male ; Biomarkers/blood ; Aged ; *Dementia/blood/diagnosis/epidemiology ; *tau Proteins/blood ; Prognosis ; *Cognitive Dysfunction/blood/epidemiology/diagnosis ; Incidence ; *Cognition/physiology ; Aged, 80 and over ; Alzheimer Disease/blood ; },
abstract = {BACKGROUND AND OBJECTIVES: Plasma biomarkers such as phospho-tau species are increasingly used in clinical practice for the diagnosis of Alzheimer disease (AD). Phosphorylated-tau at threonine 181 (p-tau181) values also provide prognostic information about incident dementia. Cognitive status similarly conveys prognostic information, but the relationship between plasma biomarkers for AD and cognitive status requires clarification.

METHODS: Participants from the Atherosclerosis Risk in Communities (ARIC) study who were adjudicated as free of dementia in 2011-2013 had plasma samples analyzed for p-tau181 and other biomarkers. Participants were surveilled for incident dementia through December 31, 2022. Cumulative incidence curves, Cox models, and Fine-Gray models were used to evaluate the independent and combined discriminatory accuracy of cognitive status and plasma biomarkers for incident dementia.

RESULTS: The sample comprised 1,577 ARIC participants (age 76.5 years, 60% women, 73% White, 27% Black). The risk of incident dementia was higher in persons with a baseline status of mild cognitive impairment (covariate-adjusted hazard ratio [HR] 2.94, 95% CI 2.61-3.33) compared with those who were cognitively unimpaired independent of biomarker status. The risk of dementia was also higher in persons with more abnormal concentrations of p-tau181 and other biomarkers independent of cognitive status. When age, cognitive status, and p-tau181 were included in the same models, the risk was attenuated relative to models where only cognitive status or plasma biomarkers were included. For continuous p-tau181 concentrations, the covariate-adjusted HR without cognitive status was 1.45 (95% CI 1.36-1.54), but when cognitive status was included, the HR decreased to 1.37 (95% CI 1.29-1.46). Models showed that when combined with age, p-tau181 alone, cognitive status alone, or the combination of p-tau181 and cognitive status had similar discriminatory accuracy.

DISCUSSION: Cognitive status and plasma biomarker concentrations convey independent but overlapping information about the risk of incident dementia. Although cognitive status and plasma p-tau181 have similar discriminatory accuracies, the far lower incidence rate of dementia in persons who are initially cognitively unimpaired highlights the importance of an accurate clinical diagnosis.},
}

Humans
Female
Male
Biomarkers/blood
Aged
*Dementia/blood/diagnosis/epidemiology
*tau Proteins/blood
Prognosis
*Cognitive Dysfunction/blood/epidemiology/diagnosis
Incidence
*Cognition/physiology
Aged, 80 and over
Alzheimer Disease/blood

@article {pmid41844011,
year = {2026},
author = {Wu, L and Dong, YT and Mu, X and Luo, X and Chen, ZJ},
title = {Integrative SMR prioritizes oxidative stress-related regulatory genes for Alzheimer's disease with brain-tissue validation.},
journal = {The journal of prevention of Alzheimer's disease},
volume = {13},
number = {5},
pages = {100535},
doi = {10.1016/j.tjpad.2026.100535},
pmid = {41844011},
issn = {2426-0266},
abstract = {Oxidative stress (OS) plays a critical role in the pathogenesis of Alzheimer's disease (AD), yet its genetic and epigenetic regulatory mechanisms remain unclear. In this study, we applied a three-step summary-based Mendelian randomization (SMR) framework to integrate Alzheimer's disease (AD) GWAS summary statistics with peripheral-blood eQTL and mQTL datasets, and further evaluated brain-tissue relevance using GTEx v8 and AMP-AD resources. Across the three-step SMR analyses, we prioritized multiple OS-related candidate genes (e.g., CRLS1, PRKAA1, CYP2E1, GPX1, and APP) associated with AD risk, and brain-tissue analyses further highlighted KEAP1, SIRT1, and PRDX5 as region-relevant signals. Functional enrichment analyses highlighted critical pathways such as "Nrf2-mediated antioxidant response" and "PI3K-AKT signaling," emphasizing the roles of oxidative stress, mitochondrial function, and neuroinflammation in AD. Novel regulatory mechanisms were uncovered at methylation sites (e.g., cg20211653 associated with ABCA1), linking epigenetic regulation to transcriptional mechanisms and providing candidates for brain-tissue follow-up. This study provides new insights into the molecular underpinnings of AD, bridging genetic variation, epigenetic regulation, and transcription, and identifies potential therapeutic targets for mitigating oxidative damage and neurodegeneration.},
}

@article {pmid41844366,
year = {2026},
author = {Duan, J and Engelman, CD and Lu, Q and Kang, H},
title = {Comparison of Methods for Sensitivity Analysis of Heterogeneous Treatment Effects in Observational Studies and Application to Alzheimer's Disease and Cognitive Decline.},
journal = {Statistics in medicine},
volume = {45},
number = {6-7},
pages = {e70446},
doi = {10.1002/sim.70446},
pmid = {41844366},
issn = {1097-0258},
mesh = {Humans ; *Alzheimer Disease/therapy ; *Cognitive Dysfunction/therapy/etiology ; *Observational Studies as Topic/statistics & numerical data/methods ; Male ; Models, Statistical ; Female ; Treatment Outcome ; Sleep Wake Disorders/complications ; Treatment Effect Heterogeneity ; },
abstract = {In Alzheimer's disease (AD) research, many observational studies have shown that the effect of sleeping quality, a modifiable risk factor, on cognitive decline is heterogeneous, where some adults experience faster rates of cognitive decline compared to others. However, these effects are likely confounded by unmeasured confounders, and the sensitivity of these effects to unmeasured confounders may be heterogeneous, where one subgroup's treatment effect is more sensitive than that of another subgroup. Unfortunately, compared to the overall treatment effect, there are limited investigations about the sensitivity of heterogeneous treatment effects to unmeasured confounding. The paper presents and compares methods for sensitivity analysis of heterogeneous effects in observational studies based on Rosenbaum's model for sensitivity analysis. We show that, unlike the sensitivity analysis of the overall treatment effect, the sensitivity of heterogeneous treatment effects depends on the variation in the effect sizes across subgroups and the correction for multiple testing. The data analysis further supports our findings where the overall effect of sleep disturbances on cognitive decline is significant (p $$ p $$ -value = 5 . 55 × 1 0 - 5 $$ 5.55\times 1{0}^
{-5}
$$). Also, the effect is more severe among males (p $$ p $$ -value = 2 . 00 × 1 0 - 4 $$ 2.00\times 1{0}^
{-4}
$$) and insensitive to a moderate degree of unmeasured confounding. Finally, we offer an easy-to-use R software to carry out the sensitivity analyses for heterogeneous treatment effects.},
}

Humans
*Alzheimer Disease/therapy
*Cognitive Dysfunction/therapy/etiology
*Observational Studies as Topic/statistics & numerical data/methods
Male
Models, Statistical
Female
Treatment Outcome
Sleep Wake Disorders/complications
Treatment Effect Heterogeneity

@article {pmid41844374,
year = {2026},
author = {Suzuki, N and Yamakawa, H and Yoshihara, K and Niidome, K and Anan, K and Takaya, K and Kouki, K and Fujimoto, K and Ono, H and Izumi, T and Unemura, K and Ito, M and Hatta, T and Kido, Y and Horiguchi, N and Kusakabe, KI},
title = {Discovery of Highly Selective HDAC2 Inhibitors in Cells That Elevate Histone Acetylation In Vivo without Adverse Effects from Dual Inhibition of HDAC1 and 2.},
journal = {Journal of medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jmedchem.5c02022},
pmid = {41844374},
issn = {1520-4804},
abstract = {Alzheimer's disease impairs the cognitive domain of learning and memory through synaptic dysfunction. Memory formation requires gene expression to facilitate synaptic plasticity. When HDAC2 is inhibited, elevated histone acetylation promotes the gene expressions critical for synaptic plasticity and thus facilitates memory formation. However, simultaneous inhibition of HDAC1 and HDAC2 leads to hematologic toxicity. As the two isoforms have high homology, it is a challenge to identify selective HDAC2 inhibitors. Here, we report the development of novel cellular assays to determine HDAC2 potency and selectivity over HDAC1. Our HTS campaign using cellular assays for both isoforms identified 6 as a selective hit compound. With optimization efforts focusing on balancing cellular potency, selectivity, and mitigating BCRP recognition, we discovered compound 11, which exhibited significant in vivo efficacy in elevating histone acetylation levels and enhancing LTP. Importantly, 11 showed no significant hematological toxicity in human blood cells derived from simultaneous inhibition of HDAC1 and HDAC2.},
}

@article {pmid41844398,
year = {2026},
author = {Hou, Y and Huang, G and Liu, Y and Qiu, Y and Ye, P and Bi, L and Zheng, P and Xu, Y and Wu, S and Wei, C and Jin, H},
title = {Rescue of Cognitive Deficits in a Mouse Model of Alzheimer's Disease with a Novel Brominated P2 × 7 Receptor Antagonist.},
journal = {ACS chemical neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1021/acschemneuro.6c00127},
pmid = {41844398},
issn = {1948-7193},
abstract = {P2 × 7 receptor (P2 × 7R) represents a promising therapeutic target for Alzheimer's disease (AD), given its marked upregulation in neuroinflammation and involvement in amyloid-β (Aβ) and tau pathology. Although several P2 × 7R antagonists with high central nervous system (CNS) penetration and cross-species activity have been developed, none have yet reached clinical use, underscoring the need for optimized agents suitable for chronic neurological conditions. In this study, we designed a series of brominated P2 × 7R antagonists based on a prominent antagonist Lu AF27139, among which the lead compound YH1 exhibited favorable lipophilicity, brain penetration, plasma stability, and receptor binding. In transgenic AD mice, YH1 treatment significantly alleviated cognitive deficits, reduced cerebral P2 × 7R expression, and decreased Aβ load. Using [18]F-GSK1482160 positron emission tomography (PET) imaging, we observed a significant decline of P2 × 7R binding, indicating that YH1-mediated cognitive improvement involves targeted suppression of P2 × 7R-driven neuroinflammation. These results establish a precision AD-oriented optimization of the Lu AF27139 scaffold, demonstrate measurable PK improvements, and provide the first PET-verified P2 × 7R target engagement in an AD model, supporting translational relevance.},
}

@article {pmid41844465,
year = {2026},
author = {Liu, J and Cao, F and Li, Z and Zeng, H and Zhou, M and He, Q and Jiang, W and Li, Y and Yan, J},
title = {Association between exogenous hormone use and dementia: A prospective cohort study and synthetic analysis.},
journal = {Maturitas},
volume = {208},
number = {},
pages = {108895},
doi = {10.1016/j.maturitas.2026.108895},
pmid = {41844465},
issn = {1873-4111},
abstract = {OBJECTIVES: To investigate the controversial association between exogenous hormone use (EHU) and dementia, with a focus on subtype-specific risks.

STUDY DESIGN: This prospective cohort study followed 273,069 women in the UK Biobank over 3,802,608 person-years, identifying 4,710 dementia cases.

MAIN OUTCOME MEASURES: Cox models assessed use of oral contraceptive (OC) and hormone replacement therapy (HRT) in relation to all-cause dementia, Alzheimer's disease (AD), vascular dementia (VaD), and frontotemporal dementia (FTD) across treatment durations. Subgroup analyses were stratified by age, ethnicity, APOE status, education, income, and reproductive factors. A systematic review was conducted to synthesize existing evidence.

RESULTS: In the cohort study, OC use was associated with reduced risks of all-cause dementia (HR 0.90, 95%CI 0.84-0.95), AD (HR 0.87, 95%CI 0.79-0.95), and VaD (HR 0.81, 95%CI 0.70-0.93), particularly after 4-14 years of use. HRT showed no significant association with increased dementia risk. Synthesized results largely corroborated these findings: OC use was associated with reduced risks of dementia (HR 0.90, 95%CI 0.89-0.92); and although four European studies reported a moderately increased AD risk after post-menopausal HRT use, neither cohort-based studies (HR 0.98, 95%CI 0.90-1.06) nor traditional case-control studies (OR 1.00, 95%CI 0.90-1.11) found an association between HRT and dementia.

CONCLUSIONS: Our combined evidence does not support an increased risk of dementia associated with OC use; similarly, no clear association was observed between HRT and increased dementia risk. Clinical decisions on EHU should be individualized, balancing overall benefits against potential risks.},
}

@article {pmid41833649,
year = {2026},
author = {Li, S and Guo, J and Wang, Y and Shi, D and Lian, X and Lu, J and Li, J},
title = {Inflammatory and metabolic pathways underlying the association between PM2.5 exposure and dementia.},
journal = {Environmental pollution (Barking, Essex : 1987)},
volume = {},
number = {},
pages = {127961},
doi = {10.1016/j.envpol.2026.127961},
pmid = {41833649},
issn = {1873-6424},
abstract = {Ambient PM2.5 exposure has been linked to dementia risk, while the underlying pathways remain unclear. This prospective cohort study was conducted in the UK Biobank, including 269,683 participants recruited at baseline between 2006 and 2010 and followed through September 1, 2023. Cox proportional hazards models were used to examine the association between annual average PM2.5 concentrations and incident dementia. Logistic regression analyses assessed the relationships between PM2.5 exposure and brain imaging characteristics. Structural equation modeling and causal mediation analysis were applied to investigate the potential mediating roles of lipid metabolites and inflammatory markers in the association between PM2.5 exposure and dementia risk. For each interquartile increase in PM2.5, the risk of all-cause dementia rose by 5% (p = 0.021), while the risk of Alzheimer's disease increased by 9% (p = 0.004). Mediation analyses indicated that lipid metabolites and inflammatory markers jointly accounted for 1.1%-3.5% of the observed associations. Neuroimaging results were consistent with these findings, showing associations with structural changes in the hippocampus and alterations in white matter microstructure. Among participants without the APOE ε4 allele, structural equation modeling further supported the presence of an inflammation-metabolism pathway linking PM2.5 exposure to dementia risk. Our findings suggest that PM2.5 may be involved in the development of dementia through interacting inflammatory and metabolic pathways, offering a more integrated biological interpretation of previously separate mechanistic observations.},
}

@article {pmid41833767,
year = {2026},
author = {Guo, Y and Li, X and Chen, Y and Li, Y and Cheng, Q and Jiang, Y and Tian, S and Yuan, B and Liu, Y and Hu, H and Li, S},
title = {Sarsasapogenin ameliorates Alzheimer's disease by dual inhibition of RIPK1-mediated necroptosis and pyroptosis.},
journal = {Cellular signalling},
volume = {},
number = {},
pages = {112481},
doi = {10.1016/j.cellsig.2026.112481},
pmid = {41833767},
issn = {1873-3913},
abstract = {Sarsasapogenin (Sar), a natural bioactive steroidal saponin derived from Anemarrhena asphodeloides, has demonstrated significant neuroprotective effects in preclinical models of Alzheimer's disease (AD). However, its specific mechanism of action, particularly in modulating receptor-interacting protein kinase 1 (RIPK1)-mediated necroptosis and pyroptosis, remains underexplored. This study aimed to investigate Sar's therapeutic potential in AD by targeting RIPK1, a central regulator of programmed cell death. We employed biolayer interferometry (BLI), cellular thermal shift assays (CETSA), and drug affinity responsive target stability (DARTS) to confirm the binding of Sar to RIPK1. In vitro, we assessed the effects of Sar on RIPK1 activation, necroptosis, and pyroptosis in SH-SY5Y neuroblastoma and BV2 microglial cells using Western blotting, immunofluorescence, and cytokine assays. In vivo, the therapeutic efficacy of Sar was evaluated in the 5 × FAD transgenic mouse model, with behavioral analysis (Morris water maze) and histological assessments of brain tissue pathology. Sar demonstrated robust binding to RIPK1 (KD = 435 nM), enhancing its thermal stability and resistance to proteolytic degradation. Treatment with Sar significantly inhibited RIPK1 phosphorylation and downstream necroptotic and pyroptotic signaling in neurons and microglia. In the 5 × FAD mouse model, Sar markedly improved spatial memory performance, reduced amyloid-beta (Aβ) plaque deposition, and decreased neuroinflammatory and necroptotic markers in both the cortex and hippocampus. Sar is a promising natural RIPK1 inhibitor capable of concurrently mitigating both necroptosis and pyroptosis-two critical pathological processes underlying AD. These findings suggest that Sar may serve as a novel disease-modifying therapeutic for AD by regulating multiple pathways involved in neurodegeneration, offering new insights into the potential of natural products in AD treatment.},
}

@article {pmid41833832,
year = {2026},
author = {Zhang, W and Liu, T and Rong, X and Liu, H and Li, M},
title = {Sympathetic overactivity-induced type H endothelial cell senescence contributes to the impairment of vascularized osteogenesis by PKM2-mediated glycolysis in preclinical stages of Alzheimer's mice.},
journal = {Bone},
volume = {},
number = {},
pages = {117859},
doi = {10.1016/j.bone.2026.117859},
pmid = {41833832},
issn = {1873-2763},
abstract = {Alzheimer's disease (AD) is characterized by early-onset bone loss, yet the underlying mechanisms remain elusive. Here, we demonstrated that sympathetic hyperactivity drives vascularized osteogenesis impairment in preclinical AD through a novel PKM2-glycolysis-mediated bone vascular endothelial cell (EC) senescence pathway. Utilizing systematic transcriptome profiling complemented by in vitro functional assays and in vivo validation studies, we found that norepinephrine (NE)-induced PKM2 downregulation disrupts glycolytic flux, triggering mitochondrial dysfunction-induced senescence (MiDAS) in vascular ECs. This metabolic reprogramming of vascular ECs inhibits the differentiation of osteoprogenitors by reducing the secretion of pro-osteogenic factors. Pharmacological inhibition of β-adrenergic signaling or PKM2 activation rescues EC senescence and bone loss. Mechanistically, NE released by the sympathetic nerve suppresses c-Maf, a transcription factor critical for PKM2 expression, linking sympathetic activation to metabolic dysfunction. Furthermore, our results also showed that combination therapy with oryzanol (sympathetic modulator) and eldecalcitol (senolytic) synergistically restores vascularized osteogenesis by targeting both neurovascular and metabolic axes. These findings establish a pathogenic role for sympathetic hyperactivity in AD-related skeletal dysfunction and highlight a therapeutic strategy targeting EC senescence and glycolytic metabolism.},
}

@article {pmid41833859,
year = {2026},
author = {Carroll, T and Pfendler, D and Alhaj Arhayem, H and Thoma, R and Müller-Eigner, A and Straut, A and Johnson, GVW and Nehrke, K},
title = {Tunable tau expression in C. elegans neurons reveals that early-AD tau phosphorylation selectively impacts behavior and mitochondrial quality control.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107350},
doi = {10.1016/j.nbd.2026.107350},
pmid = {41833859},
issn = {1095-953X},
abstract = {Tau protein accumulates myriad post-translational modifications as Alzheimer's disease (AD) progresses, and early-disease tau modifications such as phosphorylation at threonine 231 (T231) likely play a key role in AD pathogenesis. Here, a series of "tunable tau" strains was developed in C. elegans to test the relative impact of tau pseudo-phosphorylation of T231 (T231E) compared to protein expression level as a driver of phenotypic penetrance and severity. Multiple copies of a cassette coding for pan-neuronal wildtype tau or T231E were inserted at a genomic safe harbor loci to create a repertoire of strains expressing tau from low to high levels. In stereotypical behavioral assays of locomotory activity, T231E selectively impacted phenotypic severity compared to wild-type human tau controls, which further tracked with age and tau expression level. However, deficits in associative memory were non-selective between tau and T231E. Moreover, genetic, pharmacologic, and molecular approaches indicated that mitophagy modulation could suppress T231E phenotypes. Additionally, a robust mitochondrial unfolded protein response (UPRmt) occurred in T231E, and loss of atfs-1, a transcription factor central to the UPRmt suppressed T231E toxicity. These results demonstrate that phenotypic severity is invariably associated with tau dosage, while early-AD relevant modifications can be causative drivers of selective deficits. Consistent with recent findings, enhancing mitophagy or suppressing potentially maladaptive consequences of persistent UPRmt induction can be beneficial. This provides a solid foundation for further interrogation into mitochondrial quality control disruption as a potential root cause for AD pathogenesis.},
}

@article {pmid41834054,
year = {2026},
author = {Chatanaka, MK and Soosaipillai, A and Cano, A and Orellana, A and Boada, M and Prassas, I and Morató, X and Diamandis, EP},
title = {Validation of human kallikrein 6 in the cerebrospinal fluid of patients with progressive and non-progressive alzheimer's disease: correlation with other biomarkers.},
journal = {Clinical proteomics},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12014-025-09577-x},
pmid = {41834054},
issn = {1542-6416},
abstract = {BACKGROUND: Alzheimer's disease (AD) biomarkers in plasma and cerebrospinal fluid (CSF) are useful for disease diagnosis, prognosis, risk assessment and monitoring therapy response, as well as for uncovering altered disease pathways. Previously, we and others cloned a novel gene, KLK6, which encodes a serine protease of the kallikrein family. The protein (hK6) is highly expressed in the brain, spinal cord and cerebellum.

METHODS: To examine the correlation of hK6 concentration in CSF with various clinicopathological variables in AD, we used a quantitative ELISA system. The variables examined included patient age, sex, MMSE score, APOE status, amyloid β 1-42 (Αβ1-42), phosphorylated Tau 181 (p-Tau181), total Tau (t-Tau). Previously, using a cohort of Swedish and Norwegian patients, we established a positive correlation between CSF hK6 and age as well as the levels of core AD biomarkers in four groups of patients (cognitively normal, MCI without progression to AD, MCI with progression to AD within 2 years and AD dementia). In this investigation, our goal was to validate these previous data with a large and independent patient cohort from Spain.

RESULTS: We found that CSF hK6 is minimally or not affected by patient age and sex, but it significantly correlates with MMSE score and CSF Aβ1-42, p-Tau1811 and t-Tau.

CONCLUSIONS: We conclude that these correlations further support our previous findings and suggest that hK6 may be an additional biomarker for AD and may play some role in the pathogenesis of AD.},
}

@article {pmid41834096,
year = {2026},
author = {Brown, CA and Cousins, KAQ and Korecka, M and McGrew, E and Chen-Plotkin, A and Detre, JA and McMillan, CT and Lee, EB and Das, SR and Mechanic-Hamilton, D and Yushkevich, PA and Nasrallah, IM and Shaw, LM and , and Wolk, DA},
title = {Temporal Modeling of Amyloid and Tau Trajectories in Alzheimer's Disease Using PET and Plasma Biomarkers.},
journal = {Annals of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ana.78194},
pmid = {41834096},
issn = {1531-8249},
abstract = {OBJECTIVE: This study aimed to compare positron emission tomography (PET) and plasma-based temporal modeling of amyloid and tau biomarkers in Alzheimer's disease.

METHODS: Longitudinal amyloid PET (n = 1,097, mean age ± SD = 72.5 ± 7.38 year, 51.4% male), [18]F-flortaucipir tau-PET (n = 230, 74.3 ± 7.18 year, 52.2% female), and Fujirebio Lumipulse plasma p-tau217 (n = 752, 72.8 ± 6.93 year, 51.3% male) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and University of Pennsylvania Alzheimer's Disease Research Center (Penn ADRC) were used to generate biomarker trajectory models using sampled-iterative Local approximation (SILA). SILA models using plasma p-tau217 were compared to amyloid and tau PET-based models to estimate amyloid and tau onset, and factors influencing tau onset and time from tau onset to dementia were evaluated for PET and plasma models.

RESULTS: Plasma and PET models generated similar results for estimated amyloid and tau onset, with stronger model agreement for tau (r = 0.88[0.86, 0.89], t = 57.4, p < 0.001) than amyloid (r = 0.75[0.72, 0.77], t = 37.4, p < 0.001) onset. Accuracy of estimated onset compared to actual onset was high within modality (mean absolute error [MAE] ≤ 2.03) with slightly greater error (MAE 3.09-3.42) when comparing across modalities (ie, plasma to PET). For both plasma and PET, earlier tau onset was associated with younger amyloid onset, female sex, and ≥1 apolipoprotein (ApoE) ε4 allele. Earlier dementia onset after tau was associated with later tau onset for both plasma and PET, while male sex was associated with shorter tau to dementia gap in plasma models.

INTERPRETATION: Temporal modeling of plasma biomarkers provides comparable information to PET-based models, particularly for tau onset age, and can serve as a widely accessible tool for clinical assessment of biological disease severity. ANN NEUROL 2026.},
}

@article {pmid41834385,
year = {2026},
author = {Bouhour, C and Konstantopoulou, S and Piton, T and Tingaud, M and Mauriello, C and Lory, K and Unschuld, PG and Bréchet, L},
title = {Family caregiver perspectives on administering home-based stimulation in patients with mild cognitive impairment.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261429857},
doi = {10.1177/13872877261429857},
pmid = {41834385},
issn = {1875-8908},
abstract = {BackgroundWhile transcranial alternating current stimulation (tACS) shows therapeutic promise for neurological and psychiatric disorders when applied repeatedly, its potential is constrained by multiple laboratory visits.ObjectiveTraining caregivers to administer tACS at home could make therapy more practical, especially for vulnerable populations such as individuals with mild cognitive impairment (MCI). This study aimed to evaluate caregivers' perceptions and experiences of administering home-based tACS to MCI patients under remote clinical supervision.MethodsTwenty family caregivers (M age: 70 ± 12 years, 11 female) were trained to operate a six-electrode tACS device and administered 20 home-based sessions to MCI patients under real-time remote supervision. Quantitative ratings assessed caregivers' confidence, burden, and perceived benefits.ResultsCaregivers demonstrated high confidence in technical procedures (85-100% across tasks) and rated training as very satisfactory. The majority (85%) would feel comfortable administering tACS independently without remote support. Although most caregivers (70%) experienced daily life interference, nearly all (90%) would reuse the system. Clinically, 45% of caregivers observed patient benefits, and 57% of MCI patients believed sessions were beneficial. Effects on quality of life and memory were mixed, with some reporting mild deterioration, possibly reflecting natural disease progression or the double-blind design.ConclusionsCaregiver-administered home-based tACS proved feasible and acceptable among older caregivers (average age 70), despite daily life interference and mixed clinical perceptions. These findings support the expansion of caregiver-delivered protocols while emphasizing the importance of enhanced training and ongoing remote support to reduce the burden and optimize outcomes.Clinical trial registryhttps://clinicaltrials.gov/study/NCT05708001.},
}

@article {pmid41834394,
year = {2026},
author = {Yuan, M and Zhou, HY},
title = {CTAD 2025: Key trends redefining therapeutic and diagnostic strategies in Alzheimer's disease.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261430764},
doi = {10.1177/13872877261430764},
pmid = {41834394},
issn = {1875-8908},
abstract = {This article synthesizes key themes emerging from the CTAD 2025 meeting, highlighting significant advances in Alzheimer's disease (AD) research and clinical practice. New disease-modifying approaches-ranging from next-generation anti-amyloid-β and anti-tau antibodies to small-molecule aggregation inhibitors and gene-based strategies-underscore a growing shift toward multi-target therapeutic frameworks. Blood-based biomarkers, such as p-tau217, p-tau181, glial fibrillary acidic protein, and neurofilament light, are nearing clinical readiness, while digital biomarkers and wearable technologies are enabling remote, continuous assessment of cognitive and physiological functions. Clinical trial design is increasingly oriented toward earlier disease stages and genetically or biomarker-defined high-risk groups, incorporating adaptive methodologies and real-world data to enhance efficiency and generalizability. Collectively, these developments signal an impending transition over the next two to three years from a centralized, cognitive scale-driven model of AD care to a more decentralized, biomarker-guided precision paradigm. CTAD 2025 thus marks a pivotal inflection point in the evolving structure of AD diagnosis and treatment.},
}

@article {pmid41834402,
year = {2026},
author = {Al-Hammadi, M and Fleyeh, H and Thomas, I},
title = {Gait and movement analysis for discrimination between people with dementia and healthy control persons based on pose estimation and machine learning.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261430001},
doi = {10.1177/13872877261430001},
pmid = {41834402},
issn = {1875-8908},
abstract = {BackgroundDementia disorders are affecting millions of people globally, characterized by memory loss, communication difficulties, and motor function decline. Accurate and early dementia detection is crucial for effective management and treatment. Gait analysis offers a non-invasive method for dementia detection by identifying subtle changes in walking patterns that often precede cognitive symptoms.ObjectiveThis study aims to evaluate the clinical utility of video-based gait analysis using the Timed Up and Go (TUG) test under single and dual-task conditions (TUGdt) for distinguishing individuals with dementia disorders from healthy controls (HCs).MethodThe study implemented three machine learning models: Support Vector Machine (SVM), Logistic Regression (LR), and Random Forest (RF), to discriminate between persons with dementia and HCs. The dataset consists of a cohort of 64 people with dementia (47 with Alzheimer's disease) and 67 HCs. The participants performed the TUG test as a single and dual-task (TUGdt). In the TUGdt, participants performed the TUG test while simultaneously completing an additional cognitive task (i.e., animal naming (TUGdt-NA) or reciting months in reverse order (TUGdt-MB)).ResultsThe results showed that dual-task classification outperformed the single-task. The SVM algorithm achieved the highest accuracy in the TUGdt-NA task (accuracy of 87% ± 5.1 and recall of 86.6% ± 3.2) using 5-fold cross-validation and accuracy of 85.5% and recall of 89.5% using Leave-One-Out Cross-Validation (LOOCV) in the TUGdt-MB task.ConclusionsIn summary, video-based gait features effectively distinguish people with dementia from HCs, particularly under dual-tasking, offering cost-effective, automated, and non-invasive pre-screening to complement clinical assessments.},
}

@article {pmid41834411,
year = {2026},
author = {Yue, J and Carriquiriborde, V and Cheng, WH and Yildirim, T and Fan, J and Tok, S and Kelly, ML and Wellington, CL and Kent, BA},
title = {Repetitive Mild Traumatic Brain Injury Causes Neuronal Damage in the APP/PS1 Mouse Model of Alzheimer's Disease Without an Enduring Impact on Amyloid Pathology, Sleep, or Epileptiform Activity.},
journal = {Journal of neurotrauma},
volume = {},
number = {},
pages = {8977151261430301},
doi = {10.1177/08977151261430301},
pmid = {41834411},
issn = {1557-9042},
abstract = {Traumatic brain injury (TBI) is a known risk factor for Alzheimer's disease and related neurodegenerative diseases. Sleep disturbances and epileptiform abnormalities can appear after TBI and may contribute to the development of neuropathology. In this study, we characterized sleep, epileptiform activity, and neuropathology after repetitive mild traumatic brain injury (rmTBI) in a mouse model of Alzheimer's disease. We used the Closed Head Impact Model of Engineered Rotational Acceleration to deliver rmTBI or sham (control) treatment to 6-month-old APP/PS1 mice (N = 19). One month post-injury, we implanted electroencephalogram and electromyographic electrodes, recorded for 72 h, and then collected brain tissue and blood plasma. Our assessment of sleep architecture showed that time spent in vigilance state was not affected by the rmTBI 1 month post-injury; however, power spectra analysis showed a shift toward higher frequencies in the rmTBI group during non-rapid eye movement sleep. Epileptiform activity did not differ between sham and rmTBI. Compared with sham controls, the rmTBI group showed higher neurofilament light (NF-L), but not glial fibrillary acidic protein in blood plasma and no change in Aβ pathology. These results indicate sustained neurological injury in the APP/PS1 mice 1 month after rmTBI without affecting amyloid deposition in the brain. Our study suggests that rmTBI can induce neural injury without causing enduring sleep disruption, seizures, and exacerbation of amyloidosis in the APP/PS1 mouse model.},
}

@article {pmid41834535,
year = {2026},
author = {Luca, A and Luca, M and Ferri, R and Lanza, G and Serretti, A},
title = {Neuropsychiatric and behavioural correlates of sundowning in Alzheimer's disease.},
journal = {International journal of psychiatry in clinical practice},
volume = {},
number = {},
pages = {1-7},
doi = {10.1080/13651501.2026.2642681},
pmid = {41834535},
issn = {1471-1788},
abstract = {OBJECTIVES: The aims of this study were to estimate the frequency of 'sundown syndrome' (SS) in a large sample of patients with Alzheimer's disease (AD) and to assess its associated socio-demographic and clinical variables.

METHODS: Three hundred and sixty-one AD patients (age 78.4 ± 8.3 years) collected within the National Institute of Mental Health Genetics Initiative were included. A subsample was autopsy-confirmed. SS was identified within a caregiver-structured interview. Sociodemographic, clinical and neuropsychiatric features of sundowners and non-sundowners were compared by logistic regression.

RESULTS: One hundred eighty-five patients (51.2%) were sundowners. SS was positively associated with several neuropsychiatric symptoms (i.e., hallucinations, suspiciousness, wandering and aggression; all p-values < 0.01), and negatively associated with Mini-Mental State Examination and voluptuary habits (all p values < 0.05). Subsample analysis carried out in the autopsy group confirmed the findings.

CONCLUSIONS: SS is common in AD and is associated with several neuropsychiatric features and voluptuary habits. The identification of SS predictive factors may allow preventive and targeted therapeutic interventions.},
}

@article {pmid41834587,
year = {2026},
author = {Shimizu, K and Yasuda, S and Maeshima, H and Ichikawa, T and Baba, H},
title = {Serum Amyloid β Oligomer May Predict Treatment Response in Middle-Aged and Late-Life Patients With Depression.},
journal = {Neuropsychopharmacology reports},
volume = {46},
number = {2},
pages = {e70109},
doi = {10.1002/npr2.70109},
pmid = {41834587},
issn = {2574-173X},
mesh = {Humans ; Male ; Female ; *Amyloid beta-Peptides/blood ; Middle Aged ; Aged ; *Antidepressive Agents/therapeutic use ; *Major Depressive Disorder/drug therapy/blood ; *Peptide Fragments/blood ; Treatment Outcome ; Biomarkers/blood ; Adult ; Aged, 80 and over ; },
abstract = {AIM: Late-life patients with depression are reportedly less responsive to antidepressant treatment than younger patients. Additionally, patients who have depression comorbid with Alzheimer's disease (AD) and those with an amyloid β (Aβ) burden have shown a poor response to antidepressant treatment, suggesting that AD pathology may contribute to treatment resistance. A recent report indicated that Aβ oligomers in blood have increased in patients with AD and are associated with AD pathology. This study was performed to reveal the relationship between blood Aβ oligomers and the response to antidepressant treatment in middle-aged and late-life patients with depression.

METHODS: In this observational study, serum levels of Aβ40, Aβ42, and Aβ oligomers were evaluated in 80 inpatients with major depressive disorder aged ≥ 40 years. Depressive symptoms were assessed at admission (baseline) and after 4 weeks of treatment.

RESULTS: There were significantly fewer treatment responders among patients with than without serum Aβ oligomers (p = 0.016). Serum Aβ oligomers were found to influence the treatment response even after control for age, sex, number of depressive episodes, severity of depression, and Mini-Mental State Examination scores (p = 0.031).

CONCLUSIONS: These results suggest that serum Aβ oligomers may predict a poor response to antidepressant treatment in middle-aged and late-life patients with depression. Our findings also lead us to speculate that elderly patients with a poor treatment response may share AD-related pathophysiological features or neural vulnerability.},
}

Humans
Male
Female
*Amyloid beta-Peptides/blood
Middle Aged
Aged
*Antidepressive Agents/therapeutic use
*Major Depressive Disorder/drug therapy/blood
*Peptide Fragments/blood
Treatment Outcome
Biomarkers/blood
Adult
Aged, 80 and over

@article {pmid41834650,
year = {2026},
author = {Weise, CM and Abu-Rumeileh, S and Otto, M},
title = {From 'senile dementia' to non-vascular Alzheimer's synucleinopathy: the evolution of dementia classification.},
journal = {Brain : a journal of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/brain/awag103},
pmid = {41834650},
issn = {1460-2156},
}

@article {pmid41834887,
year = {2026},
author = {Brühl, SM and Volk, HA and Rohn, K and Meyerhoff, N},
title = {Myoclonus in geriatric dogs and its association with canine cognitive dysfunction: an online survey.},
journal = {Frontiers in veterinary science},
volume = {13},
number = {},
pages = {1745264},
pmid = {41834887},
issn = {2297-1769},
abstract = {BACKGROUND: An increasing number of dogs are presented with suspected canine cognitive dysfunction (CCD), and a subset also exhibits myoclonus.

OBJECTIVES: Because CCD shares multiple pathological and pathophysiological features with Alzheimer's disease in humans, and myoclonus has been linked to neurodegenerative disorders in people, the aim of the study was to describe myoclonus in dogs with clinical signs of CCD.

MATERIAL AND METHODS: An anonymous online survey for owners of geriatric dogs (over 7 years of age), consisting of 46 questions, was conducted. The survey included items on signalment, the Canine Dementia Scale (CADES), and myoclonus. CCD was defined based on a CADES score of >8. It was available online in both German and English from April to June 2024.

RESULTS: Of the 401 participants, 148 dogs were excluded due their young age, under 7 years and incomplete CADES-Score. Among the remaining respondents, 89% of owners reported that their dog showed signs of CCD. Overall, 146/164 (89.0%) dogs exhibited both CADES-defined CCD and myoclonus. However, no statistical significance was found between the co-occurrence of CCD screen status and the presence of myoclonus (p = 0.45). Predominantly, myoclonus occurred spontaneously (72.6%, n = 119), stress-induced (15.2%, n = 25), and light-induced (11.6%, n = 19). Noise-induced and feeding-induced myoclonus were the least common trigger (3.0%, n = 5 each), as well as no answer given (0.6%, n = 1). Ten dogs had multiple trigger causes.

CLINICAL SIGNIFICANCE: Myoclonus was commonly co-reported alongside CADES-defined CCD by respondents. Although no statistically significant association between CCD and myoclonus was detected, CCD should be considered among the differential diagnosis in geriatric dogs presenting with myoclonus, particularly in the context of concurrent cognitive decline.},
}