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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

@article {pmid41922721,
year = {2026},
author = {Zhao, F and Wang, S and Wang, Z and Cui, Y and Zhao, Y and Yuan, Z},
title = {Scalable discovery of spatial multicellular patterns via neighborhood-to-sequence transformation.},
journal = {Communications biology},
volume = {},
number = {},
pages = {},
doi = {10.1038/s42003-026-09923-1},
pmid = {41922721},
issn = {2399-3642},
support = {23YF1403000//Shanghai Science and Technology Development Foundation (Shanghai Science and Technology Development Fund)/ ; },
abstract = {Mining multi-cellular spatial patterns associated with biological events from high-resolution spatial omics data remains a fundamental challenge. While current computational methods have advanced from pairwise associations to identifying higher-order spatial domains, they often lack the granularity to resolve subtle local architectural shifts or the statistical framework to quantify condition-specificity. Here, we present FDPMining (Frequent and Distinctive spatial Patterns Mining), a computational framework that reformulates the biological problem of pattern discovery into a scalable data mining task through a Neighborhood-to-Sequence (N2S) encoding strategy. This transformation uniquely converts spatial grid neighborhoods for each cell into lossless and reversible numerical sequences, enabling efficient and scalable discovery of FDPs (Frequent and Distinctive spatial Patterns) via data mining algorithms. Our approach systematically explores the vast combinatorial space of cellular arrangements to identify FDPs associated with specific biological conditions. To enable spatial traceability, we further develop FDPs-Mapping, a spatial reconstruction component that maps identified patterns back to their original tissue context. This advancement allows researchers to examine and interpret patterns directly in situ. In extensive benchmarking, FDPMining demonstrates superior sensitivity in capturing subtle and condition-specific differences, outperforming state-of-the-art pairwise and higher-order pattern discovery methods. We applied our framework across diverse biological systems and spatial omics technologies, successfully identifying biologically meaningful spatial multicellular patterns in axolotl brain regeneration, brain aging, liver zonation, Alzheimer's disease, and colorectal cancer. Notably, FDPMining enables landmark-anchored pattern discovery around specific anatomical or pathological features such as blood vessels or amyloid plaques, among which applications to Alzheimer's disease revealed previously inaccessible insights into the multicellular organization of these microenvironments. FDPMining offers a paradigm for quantitatively dissecting spatial heterogeneity in complex tissues, enabling more systematic mining, visualization, and interpretation of cellular organization across diverse biological conditions.},
}

@article {pmid41922822,
year = {2026},
author = {Song, P and Wang, M and Liu, T and Zhang, Z and Ren, X and Liu, Y and Ng, JPL and Wong, VKW and Law, BYK and Fu, X and Qu, L},
title = {Medicinal seahorses (Hippocampus spp.) for Alzheimer's disease within species conservation framework: an integrated review of ethnopharmacology, bioactivity, bibliometrics, and network pharmacology.},
journal = {Naunyn-Schmiedeberg's archives of pharmacology},
volume = {},
number = {},
pages = {},
pmid = {41922822},
issn = {1432-1912},
support = {002/2023/ALC, 006/2023/SKL//Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery funded by Macau Science and Technology Development Fund/ ; No.LCKY202519//Scientific Research Fund Project of Shandong University of Traditional Chinese Medicine/ ; No. zyyzdxk-2023124//NATCM's Project of High-level Construction of Key TCM Disciplines/ ; },
abstract = {Seahorses (Hippocampus spp.) have been used in traditional Chinese medicine for centuries and are now regarded as underexplored but promising marine resources for modern drug discovery. This review reassesses medicinal seahorses as a potential marine resource for identifying multi-target candidates relevant to Alzheimer's disease (AD) by integrating taxonomy and distribution, conservation, and aquaculture status, ethnomedicinal use, chemical composition, and pharmacology, as well as bibliometric and network-pharmacology analyses. Using published surveys and global databases, we collated records indicating 16 Hippocampus species in Chinese waters and identify five pharmacopeial taxa whose dependence on fragile coastal habitats contrasts with the recent expansion of captive-breeding, tank and pond-based culture, suggesting that regulated aquaculture can supply traceable raw material and alleviate pressure on wild populations. Bibliometric mapping of Web of Science records (1979-2024) shows a shift from aquaculture and conservation towards antioxidant, anti-inflammatory, neuroprotective, and AD-related research. Across the five medicinal species, 329 reported constituents reflect substantial chemical diversity that may contribute to antioxidant, anti-inflammatory, neuroprotective, endocrine and immunomodulatory activities with potential relevance to AD-related pathophysiology. Network-pharmacology analysis links 276 structurally defined compounds to an AD-associated gene module, highlighting a core module centered on APP, JUN and PPARγ as putative mechanistic nodes. This article is based solely on published data and involves no new field collection or experimentation on wild seahorses. We propose that future work should rely on species-verified, aquaculture-derived material, rigorous chemical characterization, and quality control, AD-focused mechanistic and pharmacokinetic studies, and synthetic or biotechnological production of key constituents to support the ethically and ecologically responsible exploration of Hippocampus-based candidates relevant to AD.},
}

@article {pmid41922883,
year = {2026},
author = {Shah, D and Akarte, K and Patel, S and Patel, A and Kushwaha, N and Panjwani, D and Patel, V and Ahlawat, P and Shah, A},
title = {Recent Progress on Selenium Nanoparticles: Synthesis and Neuroprotective Effects for the Treatment of Alzheimer's Disease.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {41922883},
issn = {1559-1182},
mesh = {*Alzheimer Disease/drug therapy ; Humans ; *Neuroprotective Agents/chemical synthesis/therapeutic use/pharmacology ; Animals ; *Nanoparticles/chemistry/therapeutic use ; *Selenium/therapeutic use/chemistry ; },
abstract = {Alzheimer's disease (AD) is the most prevalent cause of dementia, affecting over 50 million individuals worldwide, with projections suggesting a tripling of cases by 2050. Current Food and Drug Administration (FDA)-approved treatments, including cholinesterase inhibitors, N-Methyl-D-aspartic acid (NMDA) receptor antagonists, and monoclonal antibodies, provide only modest symptomatic relief or partial disease modification. Their limitations include poor blood-brain barrier penetration, systemic side effects, and reduced efficacy in advanced stages. This has caused the exploration of novel nanotechnology-based interventions. This review synthesizes recent evidence from preclinical and translational studies on SeNPs for AD therapy. Also covering their synthesis methods (physical, chemical, and biological), surface engineering approaches, drug loading strategies, and mechanisms of action were systematically examined. SeNPs exhibit dual functionality as therapeutic agents and drug carriers. Functionalized SeNPs have shown the ability to cross the BBB, but this efficiency depends on particle size (typically < 100 nm) and surface ligands such as transferrin, rabies virus glycoprotein 29-peptide (RVG29), or transferrin-guiding peptide (TGN). Studies using ligand-modified SeNPs demonstrate improved BBB transport and enhanced modulation of oxidative stress, amyloid-β (Aβ) aggregation, and neuroinflammation. SeNPs exhibit neuroprotective activity in several preclinical models, primarily attributed to antioxidant and anti-inflammatory mechanisms. Although encouraging preclinical data support their promise, systematic toxicological assessment and optimization of stability are required. With advances in green synthesis, surface engineering, and theranostic applications, SeNPs may represent a new Framework in precision nanomedicine for Alzheimer's disease.},
}

*Alzheimer Disease/drug therapy
Humans
*Neuroprotective Agents/chemical synthesis/therapeutic use/pharmacology
Animals
*Nanoparticles/chemistry/therapeutic use
*Selenium/therapeutic use/chemistry

@article {pmid41913218,
year = {2026},
author = {Shao, S and Ribeiro, PH and Orlenko, A and Cardone, KM and Ramirez, CM and Shen, L and Ritchie, MD and Moore, JH},
title = {A biology-based quality-diversity algorithm for drug repurposing in Alzheimer's disease using automated machine learning.},
journal = {BioData mining},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13040-026-00550-4},
pmid = {41913218},
issn = {1756-0381},
}

@article {pmid41913245,
year = {2026},
author = {Kim, SJ and Kim, MJ and Kim, JS and Jang, J and Choi, W and Lee, HJ and Song, JH and Hoe, HS},
title = {AI-enabled digital phenotyping for Alzheimer's disease: a review of multimodal sensor integration and symptom trajectories.},
journal = {Alzheimer's research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13195-026-02013-8},
pmid = {41913245},
issn = {1758-9193},
support = {RS-2024-00357857//NRF/ ; RS-2024-00343370//KDRC/ ; H0501-25-1001//NIPA/ ; 26-BR-02-04, 26-BR-05-01, and 26-BR-06-01//KBRI/ ; },
}

@article {pmid41913259,
year = {2026},
author = {Opwonya, J and Ku, B and van der Heide, F and Lee, KH and Kim, JI and Kim, JU},
title = {Linking eye movements, pupil responses, and brain networks in early cognitive decline.},
journal = {Alzheimer's research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13195-026-02035-2},
pmid = {41913259},
issn = {1758-9193},
support = {KSN2313022//Korean Government/ ; KSN2313022//Korean Government/ ; },
}

@article {pmid41913274,
year = {2026},
author = {Delgado, A and Davidson, K and Parker, D and Bryant, J and Winstead, V and Yildiz, M and Pickering, CEZ and Pickering, AM},
title = {Weekly fluctuations of plasma amyloid-beta in Alzheimer's disease: implications for biomarker reliability.},
journal = {Alzheimer's research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13195-026-02040-5},
pmid = {41913274},
issn = {1758-9193},
support = {Aging R01 RMH121928C/MH/NIMH NIH HHS/United States ; Aging R01 RMH121928C/MH/NIMH NIH HHS/United States ; R01 AG06531/AG/NIA NIH HHS/United States ; },
}

@article {pmid41913828,
year = {2026},
author = {Frolov, A and Maglasang, M and Guzman, M and Echols, MS and Daly, DT},
title = {Coexistence of Rheumatoid Arthritis, Cerebrovascular Disease, and Alzheimer's Disease: A Case Study With Genetic Insights.},
journal = {Cureus},
volume = {18},
number = {2},
pages = {e104395},
pmid = {41913828},
issn = {2168-8184},
abstract = {To gain new insights into the molecular underpinnings of coexisting rheumatoid arthritis (RA), cerebrovascular disease (cVD), and Alzheimer's disease (AD), we performed postmortem neuropathological examination and genetic screening of two individuals. The first individual (donor 1, D1) was a 74-year-old man who was diagnosed with both RA and AD and who also underwent hip replacement surgery bilaterally. The second individual (donor 2, D2) was a 90-year-old man with a reported diagnosis of RA, as well as two left hip replacements. A thorough histochemical (hematoxylin and eosin, H&E) and immunohistochemical (β-amyloid and tau protein) examination of D1 and D2 brains revealed the presence of AD-related pathology in both individuals, with AD stages being mild in D1 and intermediate in D2. The cVD-related pathology was also evident in both cases and was characterized by several microbleeds indicative of a compromised blood-brain barrier (BBB) integrity. Blood vessel wall thickening, a characteristic of arteriosclerosis, was significant in D1 but minor in D2. Therefore, the earlier RA diagnoses, along with the results of the neuropathological examination, indicated the coexistence in the donors of three major diseases: RA, cVD, and AD. The whole exome sequencing (WES) of DNA procured from D1 and D2 performed on the next-generation sequencing (NGS) Illumina platform (San Diego, CA) was followed by a very stringent bioinformatics analysis that yielded multiple genes with rare (minor allele frequency {MAF}
≤ 0.01) genetic pathological/deleterious variants associated with RA, cVD, and AD. Seven of those genes, AQP7, ARSD, FAM160A1, HYDIN, IGSF3, OTOP1, and PRSS1, were shared between D1 and D2, with all but FAM160A1 having identical variants in both donors. Intriguingly, the subsequent analysis of the respective literature indicated that FAM160A1, IGSF3, and PRSS1 were pleiotropic as they could be linked to all three coexisting diseases: RA, cVD, and AD. Altogether, the data presented herein are consistent with the notion that AD, cVD, and RA, when they coexist in humans, could be underpinned by a combination of polygenic and pleiotropic factors. Yet, a significant number of affected genes in the donors associated with bone and cartilage physiology point toward the possibility of joints being also damaged directly and independently of RA.},
}

@article {pmid41913857,
year = {2026},
author = {Chen, W and Ngo, MT and Tewary, S},
title = {Evaluating Knowledge Outcomes of the Age-Friendly Health Systems and 4Ms Module in Medical Education: A Comparative Study of YouTube vs. Virtual Reality Platforms.},
journal = {Cureus},
volume = {18},
number = {2},
pages = {e104394},
pmid = {41913857},
issn = {2168-8184},
abstract = {This study evaluated and compared the effectiveness of Virtual Reality (VR) versus YouTube-based training in teaching the 4Ms framework: What Matters, Medication, Mentation, and Mobility, within a geriatric medicine course for second-year medical students. Pre- and post-training surveys were administered via REDCap, and matched sample t-tests and Cohen's d effect size were conducted. VR training resulted in a mean knowledge increase of 0.55 (2.49 to 3.04, N=90), while YouTube training showed a 0.53 increase (2.58 to 3.11, N=76). Both showed statistically significant gains (p <0.001), with YouTube having a larger t-value (-7.39 vs. -6.41), but VR demonstrating a greater effect size (Cohen's d = 0.82 vs. 0.62). However, an independent samples t-test revealed no significance in knowledge gains between groups (p = 0.80). These findings suggest that both modalities effectively enhance knowledge, with VR demonstrating a stronger effect size, likely due to its interactive effect. This highlights its potential use in medical education on geriatrics.},
}

@article {pmid41914164,
year = {2026},
author = {Sukumaran, ES and Ganamurali, N and Pm, A and Raja, A and Narasimha, MK and Sabarathinam, S},
title = {Fructose Metabolism and Disease Mechanisms: From Nutritional Excess to Obesity and Multiorgan Pathophysiology.},
journal = {Frontiers in bioscience (Elite edition)},
volume = {18},
number = {1},
pages = {46304},
doi = {10.31083/FBE46304},
pmid = {41914164},
issn = {1945-0508},
mesh = {Humans ; *Fructose/metabolism/adverse effects ; *Obesity/metabolism/physiopathology/etiology ; Animals ; },
abstract = {Excessive fructose consumption has emerged as a critical driver of obesity and metabolic dysfunction, with far-reaching implications for multiple organ systems. This review synthesizes current evidence on the biochemical and molecular pathways underlying fructose induced disease mechanisms, discussing how fructose metabolism activates the "survival switch", promotes fat storage, and generates uric acid, mitochondrial dysfunction, and oxidative stress, thereby disrupting energy homeostasis. Key organ-specific consequences are explored, including hepatic steatosis and progression to non-alcoholic fatty liver disease, pancreatic β-cell dysfunction, renal fibrosis, intestinal barrier disruption with microbial dysbiosis, cardiometabolic impairment, pulmonary inflammation, and neurocognitive decline with relevance to Alzheimer's disease. Moreover, mechanistic insights highlight the role of fructokinase C activation, adenosine triphosphate (ATP) depletion, leptin resistance, pro-inflammatory signaling (mechanistic target of rapamycin complex-1 (mTORC1), renin angiotensin system (RAS), Toll-like receptor 4 (TLR4)), and cross-talk between fructose metabolism and organ-specific pathophysiology. Animal and human studies consistently reinforce the central role of fructose overload in driving obesity and associated complications. Meanwhile, this review frames fructose not merely as a caloric contributor but as a metabolic disruptor, thereby underscoring the urgent need for public health interventions, dietary regulation, and mechanistic research to mitigate fructose-driven metabolic disease.},
}

Humans
*Fructose/metabolism/adverse effects
*Obesity/metabolism/physiopathology/etiology
Animals

@article {pmid41914285,
year = {2026},
author = {Stefano, GB},
title = {NAD[+] Homeostasis and Mitochondrial Modifiability: Resilience in Alzheimer's Disease.},
journal = {Frontiers in bioscience (Landmark edition)},
volume = {31},
number = {3},
pages = {49714},
doi = {10.31083/FBL49714},
pmid = {41914285},
issn = {2768-6698},
mesh = {Humans ; *Alzheimer Disease/metabolism/pathology ; *NAD/metabolism ; *Mitochondria/metabolism ; *Homeostasis ; Animals ; Oxidation-Reduction ; Energy Metabolism ; },
abstract = {Alzheimer's disease (AD) is increasingly associated with mitochondrial dysfunction and disrupted metabolism. Thus, the maintenance of nicotinamide adenine dinucleotide (NAD[+]) homeostasis is proposed as a potential therapeutic strategy. Toward this end, we suggest that AD-related mitochondrial dysfunction might be viewed as a regulatable, redox-dependent vulnerability rather than an inherently degenerative and irreversible process. This perspective advances an evolutionary model in which NAD[+]-mediated redox systems represent a conserved regulatory axis, and that destabilization of this axis during aging may increase susceptibility to degeneration. Here, we assess the potential of a therapeutic approach that combines this understanding of mitochondrial energy metabolism with results from preclinical studies demonstrating the impact of pharmacologic correction of NAD[+] homeostasis (e.g., P7C3-A20) as contextual motivation. We explicitly elevate redox balance, rather than absolute NAD[+] abundance, as the mechanistically dominant variable that shapes mitochondrial resilience, inflammatory tone, and neurovascular stability. Accordingly, the key unresolved issue is whether specific physiologic benefits might accrue from increased NAD[+] availability per se or rather, the restoration of the NAD[+]/NADH redox ratio, with important implications for the interpretation of the results of directed metabolic interventions. Within this framework, metabolic failure in AD can be understood as an upstream permissive condition that explains, rather than replaces, canonical amyloid-β and tau-associated pathologies. While extended human lifespan may expose late-life vulnerabilities in otherwise conserved metabolic systems, claims of causal primacy, disease reversibility, and cross-neurodegenerative generalization remain premature, underscoring the need for redox-resolved, genetic, and clinical validation.},
}

Humans
*Alzheimer Disease/metabolism/pathology
*NAD/metabolism
*Mitochondria/metabolism
*Homeostasis
Animals
Oxidation-Reduction
Energy Metabolism

@article {pmid41914304,
year = {2026},
author = {Wei, H and Wang, B and Yang, J and Liao, L},
title = {The Mechanism of PANoptosis in Alzheimer's Disease: Exploring the Multiple Network Regulation of Cell Death.},
journal = {Frontiers in bioscience (Landmark edition)},
volume = {31},
number = {3},
pages = {45499},
doi = {10.31083/FBL45499},
pmid = {41914304},
issn = {2768-6698},
support = {S20250012//Sichuan Medical Association Medical Scientific Research Project/ ; },
mesh = {*Alzheimer Disease/pathology/metabolism ; Humans ; Amyloid beta-Peptides/metabolism ; Cell Death ; tau Proteins/metabolism ; Animals ; Neurons/pathology/metabolism ; Plaque, Amyloid/pathology/metabolism ; Brain/pathology/metabolism ; *Necroptosis ; Apoptosis ; },
abstract = {Alzheimer's disease (AD) is a neurodegenerative disorder primarily affecting the geriatric population, characterized by progressive cognitive impairment and behavioral abnormalities. Due to the absence of effective disease-modifying therapies, AD imposes a substantial burden on patients and their families. The etiology and pathogenesis of AD have not been fully elucidated; multiple pathological alterations have been implicated, including the deposition of β-amyloid (Aβ) plaques, abnormal tau phosphorylation, and neuroinflammatory responses. These pathological changes contribute to neuronal damage, synaptic dysfunction, and neuronal death, ultimately leading to brain atrophy. Recent studies have identified PANoptosis as a critical regulatory mechanism of programmed cell death that influences the pathological progression of AD through multiple pathways, including modulation of Aβ plaque deposition and regulating neuroinflammatory responses. However, the precise mechanisms of these effects remain unclear. This review aims to comprehensively analyze recent research findings, focusing on the regulatory role of PANoptosis in AD, exploring the specific manifestations of the intricate network of cell death regulation in AD pathogenesis. By providing a systematic overview of emerging findings, this review offers new insights into the pathogenesis of AD and highlights potential directions for the development of targeted therapeutic strategies.},
}

*Alzheimer Disease/pathology/metabolism
Humans
Amyloid beta-Peptides/metabolism
Cell Death
tau Proteins/metabolism
Animals
Neurons/pathology/metabolism
Plaque, Amyloid/pathology/metabolism
Brain/pathology/metabolism
*Necroptosis
Apoptosis

@article {pmid41914305,
year = {2026},
author = {Xie, JL and Hu, XH and Wu, CL and Jin, Q and Pan, JP},
title = {DHA Ameliorates Alzheimer's Disease by Attenuating Microglial Pyroptosis via Regulation of the HOXA9-NLRP3 Pathway.},
journal = {Frontiers in bioscience (Landmark edition)},
volume = {31},
number = {3},
pages = {46572},
doi = {10.31083/FBL46572},
pmid = {41914305},
issn = {2768-6698},
support = {20232BAB206049//Jiangxi Provincial Natural Science Foundation General Project/ ; },
mesh = {*Alzheimer Disease/drug therapy/metabolism ; *Docosahexaenoic Acids/pharmacology/therapeutic use ; Animals ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/genetics ; *Pyroptosis/drug effects ; Mice ; Humans ; *Homeodomain Proteins/metabolism/genetics ; *Microglia/drug effects/metabolism ; Amyloid beta-Peptides ; Signal Transduction/drug effects ; Male ; Mice, Transgenic ; Disease Models, Animal ; Peptide Fragments ; Neuroprotective Agents/pharmacology ; Mice, Inbred C57BL ; Cell Line ; },
abstract = {BACKGROUND: Alzheimer's disease (AD) involves a progressive deterioration of cognitive abilities, memory loss, and persistent brain inflammation. Emerging evidence indicates that pyroptosis mediated by the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, contributes significantly to AD development. Docosahexaenoic acid (DHA) has demonstrated neuroprotective properties; however, the precise mechanisms by which it modulates pyroptosis in AD have yet to remained incompletely elucidated.

OBJECTIVE: To explore the role of DHA in modulating microglial pyroptosis via the HOXA9-NLRP3 pathway in an AD model.

METHODS: Effects of DHA on Aβ25-35-induced pyroptosis were assessed in human microglial clone 3 (HMC3) human microglial cells using CCK-8, western blotting, immunofluorescence, and Enzyme-linked Immunosorbent Assay (ELISA) assays. The role of homeobox A9 (HOXA9) in pyroptosis regulation was evaluated through overexpression and knockdown experiments. Dual-luciferase reporter assays together with chromatin immunoprecipitation (ChIP) were used to verify the interaction of HOXA9 to NLRP3 promoter. Amyloid precursor protein / Presenilin-1 double-transgenic (APP/PS1) transgenic AD mice underwent DHA treatment in vivo, and cognitive performance was assessed using the Morris water maze paradigm. Expression of HOXA9, NLRP3, and pyroptosis-related proteins were analyzed by Quantitative Real-time Reverse Transcription PCR (qRT-PCR), Western blotting, and immunofluorescence.

RESULTS: DHA treatment significantly reduced Aβ25-35-induced microglial pyroptosis, as indicated by decreased levels of p30-Gasdermin D (GSDMD), cleaved-caspase-1, IL-1β, and IL-18. HOXA9 overexpression reversed the protective effects of DHA, whereas NLRP3 inhibition by MCC950 enhanced DHA inhibition of pyroptosis. Dual-luciferase and ChIP assays confirmed that HOXA9 directly regulates NLRP3 transcription. In APP/PS1 mice, DHA administration enhanced cognitive performance while simultaneously decreasing the expression of pyroptosis-related markers and inflammatory mediators in brain. Inhibition of NLRP3 signaling by MCC950 further strengthened the neuroprotective actions of DHA.

CONCLUSION: DHA ameliorates AD-related cognitive decline and reduces microglial pyroptosis through suppressing the HOXA9-NLRP3 axis. These results offer novel insights into the molecular basis of DHA-mediated neuroprotection and highlight potential therapeutic targets for AD.},
}

*Alzheimer Disease/drug therapy/metabolism
*Docosahexaenoic Acids/pharmacology/therapeutic use
Animals
*NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/genetics
*Pyroptosis/drug effects
Mice
Humans
*Homeodomain Proteins/metabolism/genetics
*Microglia/drug effects/metabolism
Amyloid beta-Peptides
Signal Transduction/drug effects
Male
Mice, Transgenic
Disease Models, Animal
Peptide Fragments
Neuroprotective Agents/pharmacology
Mice, Inbred C57BL
Cell Line

@article {pmid41914380,
year = {2026},
author = {Chen, L and Chen, EW and Chen, BW and Wang, D},
title = {Retinol Taking a Detour Promotes Neural Stem Cell Self-Renewal In Vivo Accompanied by Down-Regulation of Some Retinoic Acid Receptors.},
journal = {Stem cells and development},
volume = {},
number = {},
pages = {15473287261436286},
doi = {10.1177/15473287261436286},
pmid = {41914380},
issn = {1557-8534},
abstract = {Since our previous studies have indicated retinol promotes self-renewal of embryonic stem cells in vitro culture, we speculate that retinol may be directly involved in regulating adult stem cell self-renewal or developmental function in vivo. Vitamin A or retinoic acid (RA) solution was first injected into the abdominal cavities of mice, and then self-renewal and development marker gene expressions were investigated. The in vivo effects of retinol and RA on RA receptor expressions were further examined. The results showed that retinol not only significantly promotes self-renewal of neural stem cells in vivo but also induces orientational development of neural stem cells in vivo and significantly downregulates the expression of some RA receptor gene expression in the brain. This study provides experimental and theoretical bases for elucidating the regulation mechanism of retinol-mediated cell development in vivo, especially in brain, and the development of therapeutic drugs for neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis, Multiple sclerosis, and Huntington's disease.},
}

@article {pmid41914594,
year = {2026},
author = {Rebolo, M and Maroco, J and Melo, G and Mendonça, A},
title = {Coping Strategies Used by Caregivers of Patients With Mild Cognitive Impairment due to Alzheimer's Disease - A Longitudinal Study.},
journal = {Journal of geriatric psychiatry and neurology},
volume = {},
number = {},
pages = {8919887261439756},
doi = {10.1177/08919887261439756},
pmid = {41914594},
issn = {1552-5708},
abstract = {BackgroundAdvances in biomarker research allow precise diagnosis of Alzheimer's disease (AD) in patients with Mild Cognitive Impairment (MCI). Communicating this diagnosis may reduce uncertainty and aid care planning but can also increase anxiety, distress, or anticipatory burden among care partners.ObjectiveTo characterise coping strategies used by caregivers of patients recently diagnosed with MCI due to AD and examine their evolution.MethodsThirty caregivers of patients with MCI due to AD were recruited from a memory clinic, assessed at baseline, and followed over 18 months. Caregiver personality, burden, depressive and anxiety symptoms, perceived relationship closeness, and distress related to patient neuropsychiatric symptoms were also assessed at baseline. Coping was assessed longitudinally using the Brief COPE, grouping its 14 subscales into problem-focused, emotion-focused, and dysfunctional coping.ResultsCaregivers used problem-focused (3.37 ± 1.02) and emotion-focused (2.91 ± 0.86) more often than dysfunctional coping (1.13 ± 0.56). Dysfunctional coping was associated with lower perceived relationship closeness, higher burden, and greater distress related to neuropsychiatric symptoms, while emotion-focused coping was inversely associated with anxiety and depression. Trends suggested associations between emotion-focused coping and extraversion, and between problem-focused coping and conscientiousness. Coping patterns remained stable over time. Caregivers reported elevated psychological distress.ConclusionCaregivers of patients with MCI due to AD experience considerable psychological distress but appear to rely primarily on adaptive coping strategies. The stability of coping patterns suggests that coping responses may begin to consolidate early in the caregiving trajectory. Given the exploratory nature of our study, further longitudinal research is needed.},
}

@article {pmid41914617,
year = {2026},
author = {Diniz, BS},
title = {Do people with bipolar disorder have a greater risk of dementia in later life?.},
journal = {Expert review of neurotherapeutics},
volume = {},
number = {},
pages = {1-3},
doi = {10.1080/14737175.2026.2652297},
pmid = {41914617},
issn = {1744-8360},
}

@article {pmid41914643,
year = {2026},
author = {Doan, VU and Xu, Y and Wang, Z and Kaminski, AM and Pedersen, LC and Liu, J},
title = {Development of a Specific and Sensitive LC-MS/MS Method to Quantify Heparan Sulfate 3-O-Sulfotransferase-1 Activity.},
journal = {Glycobiology},
volume = {},
number = {},
pages = {},
doi = {10.1093/glycob/cwag024},
pmid = {41914643},
issn = {1460-2423},
abstract = {Heparan sulfate (HS) is a highly sulfated glycan that regulates diverse biological processes through specific sulfation patterns. Among these, 3-O-sulfation catalyzed by heparan sulfate 3-O-sulfotransferase-1 (3OST-1) is rare but functionally critical, influencing anticoagulation and contributing to the progression of Alzheimer's disease and cancer progression. However, direct measurement of 3OST-1 activity in biological systems has been limited by the lack of sensitive and specific assays. Here we developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay using a structurally defined HS hexasaccharide substrate and 13C-labeled internal standards. This method enables nanogram-level detection of 3-O-sulfated products following heparinase digestion and AMAC derivatization. The LC-MS/MS assay demonstrated 100-fold improved sensitivity compared to HPLC and successfully quantified endogenous 3OST-1 activity in HCT-116 cells and conditioned media. Using this assay, we confirmed that the 3OST-1 E86Q mutant acts as a dominant-negative inhibitor. E86Q mutant retains substrate and donor binding but abolishes catalytic activity, reducing wild-type 3OST-1-like activity by >80% in vitro and significantly decreasing 3-O-sulfated HS products in cells without affecting overall HS abundance. This assay provides the first quantitative tool for 3OST-1-like activity and establishes a dominant-negative strategy for functional studies, offering new opportunities for biomarker development and therapeutic targeting in HS-related pathologies.},
}

@article {pmid41914924,
year = {2026},
author = {Stagge, F and Saylor, AK and Dallas, ON and Johnson, AL and Palmer, KM and Fromm, D and Lanzi, AM},
title = {Increasing Educator Resources for Mild Cognitive Impairment and Dementia Using a Knowledge-to-Action Framework: The Development of DementiaBank Grand Rounds.},
journal = {American journal of speech-language pathology},
volume = {},
number = {},
pages = {1-21},
doi = {10.1044/2026_AJSLP-25-00396},
pmid = {41914924},
issn = {1558-9110},
abstract = {PURPOSE: An educational gap exists in content knowledge and clinical education for speech-language pathologists concerning the treatment and assessment of cognitive-communication disorders from mild cognitive impairment (MCI) or dementia due to Alzheimer's disease (AD). This gap may result in less effective speech-language pathology services for this population. The overarching goal of this project was to enhance graduate speech-language pathology education about MCI and dementia due to AD to improve the quality of future service providers.

METHOD: To achieve this goal, this project had two objectives: first, to conduct a survey to understand speech-language pathology graduate school education practices in clinical and classroom settings regarding cognitive-communication disorders from MCI or dementia due to AD and, second, to conduct focus groups to guide the development of an online educational resource, informed by speech-language pathology graduate school educators. A knowledge-to-action (KTA) conceptual framework provided guidance to translate findings from the survey and focus groups into a highly implementable educational resource.

RESULTS: Educators of graduate speech-language pathology students reported a crucial need for additional accessible resources to assist them in teaching or supervising cognitive-communication disorders from MCI or dementia due to AD. The existing TalkBank educational resource, Grand Rounds, was explored through educator focus groups, and feedback directly informed the creation of a new educational resource tailored for this population.

CONCLUSIONS: Overall, an educational resource, DementiaBank Grand Rounds, was successfully developed for cognitive-communication disorders associated with MCI and dementia due to AD, utilizing the KTA framework. DementiaBank Grand Rounds may serve as a resource to support learners and educators and address the current gap in content knowledge and clinical education.

SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.31839664.},
}

@article {pmid41915038,
year = {2026},
author = {Xia, Y and Johnson, K and Fakhri, GE and Guehl, NJ and van de Giessen, E and Coomans, EC and Pijnenburg, YAL and Ossenkoppele, R and Groot, C},
title = {Bayesian modelling demonstrates clinically relevant heterogeneity in Tau PET patterns in Alzheimer's disease.},
journal = {European journal of nuclear medicine and molecular imaging},
volume = {},
number = {},
pages = {},
pmid = {41915038},
issn = {1619-7089},
support = {10510022110010/ZONMW_/ZonMw/Netherlands ; WE.03-2024-06//Alzheimer Nederland/ ; 949570//H2020 European Research Council/ ; },
}

@article {pmid41915112,
year = {2026},
author = {Zhou, Y and Li, S and Xiang, J},
title = {The role of MicroRNAs in Alzheimer's disease: from pathogenesis to therapeutic potential.},
journal = {Molecular biology reports},
volume = {53},
number = {1},
pages = {},
pmid = {41915112},
issn = {1573-4978},
mesh = {*Alzheimer Disease/genetics/therapy/metabolism/pathology ; Humans ; *MicroRNAs/genetics/metabolism ; Biomarkers/metabolism ; tau Proteins/metabolism/genetics ; Amyloid beta-Peptides/metabolism/genetics ; Animals ; },
abstract = {Alzheimer's disease (AD) is a major neurodegenerative disorder that severely impacts the global elderly population. It is characterized by progressive memory loss, cognitive impairment, and neuropsychiatric disturbances. To date, AD lacks definitive curative treatments, making it a persistent clinical challenge. Consequently, there is an urgent need to develop cost-effective and highly specific biomarkers for the early detection of AD. MicroRNAs (miRNAs) are evolutionarily conserved, small non-coding RNAs. They are highly enriched in the central nervous system (CNS), where they orchestrate essential processes like axonal outgrowth, dendritic arborization, and synaptic plasticity. In AD patients, miRNAs actively regulate disease progression and exhibit abnormal expression profiles in peripheral blood. By modulating target genes across key pathological pathways-including β-amyloid (Aβ) aggregation, tau hyperphosphorylation, and neuroinflammation-miRNAs act as pivotal regulators of AD initiation. Therefore, systematically investigating their diagnostic and therapeutic potential could drive the development of innovative AD management strategies.},
}

*Alzheimer Disease/genetics/therapy/metabolism/pathology
Humans
*MicroRNAs/genetics/metabolism
Biomarkers/metabolism
tau Proteins/metabolism/genetics
Amyloid beta-Peptides/metabolism/genetics
Animals

@article {pmid41915182,
year = {2026},
author = {Xu, J and Chen, L and Chen, Z and Song, Y and Fu, Z and Ao, X and Sun, X and Chen, Y and Wei, W and Sun, C and Tian, Z},
title = {Sex-specific links between dietary fat intake, dementia risk, and cognitive decline in central obesity: a UK biobank cohort study.},
journal = {European journal of nutrition},
volume = {65},
number = {3},
pages = {},
pmid = {41915182},
issn = {1436-6215},
support = {U21A20398//National Natural Science Foundation of China/ ; },
mesh = {Humans ; Female ; Male ; United Kingdom/epidemiology ; *Dementia/epidemiology/etiology ; *Cognitive Dysfunction/epidemiology/etiology ; *Obesity, Abdominal/complications/epidemiology ; Middle Aged ; *Dietary Fats/administration & dosage/adverse effects ; Aged ; Risk Factors ; Cohort Studies ; Sex Factors ; Biological Specimen Banks ; Alzheimer Disease/epidemiology ; Prospective Studies ; Incidence ; Diet ; UK Biobank ; },
abstract = {PURPOSE: To clarify the unclear association of dietary fat intake with dementia and cognitive impairment in individuals with central obesity, this study explored links of proportion of energy from dietary fat (PEFDF) to dementia risk and cognitive decline.

METHODS: A total of 128,160 participants from the UK Biobank were included in this study. Cox regression, logistics regression and univariate linear regression models were used to analyze the associations between PEFDF and the risk of dementia and cognitive impairment.

RESULTS: Among women, PEFDF showed a potential nonlinear association with all-cause dementia and Alzheimer's disease incidence, whereas no significant association was observed in men. Notably, obese women with a moderately high percentage of energy from fat (MHF) had the lowest risk of all-cause dementia (HR, 0.746; 95% CI, 0.590-0.943) and Alzheimer's disease incidence (HR, 0.606; 95% CI, 0.419-0.876). Furthermore, MHF was associated with higher fluid intelligence test (FIT) scores (β, 0.213; 95% CI, 0.185-0.241), numerical memory test (NMT) scores (β, 0.091; 95% CI, 0.062-0.119), and prospective memory test (PMT) scores (OR, 1.187; 95% CI, 1.145-1.231) in women; and MHF was significantly associated with higher FIT (β, 0.198; 95% CI, 0.169-0.228) scores and PMT scores (OR, 1.114; 95% CI, 1.073-1.156) in man.

CONCLUSIONS: Our findings showed that MHF is positively associated with neurocognitive function in central obesity, especially in women. These results underscore the potential of scientifically effective dietary intervention in mitigating risk of dementias such as Alzheimer's disease.},
}

Humans
Female
Male
United Kingdom/epidemiology
*Dementia/epidemiology/etiology
*Cognitive Dysfunction/epidemiology/etiology
*Obesity, Abdominal/complications/epidemiology
Middle Aged
*Dietary Fats/administration & dosage/adverse effects
Aged
Risk Factors
Cohort Studies
Sex Factors
Biological Specimen Banks
Alzheimer Disease/epidemiology
Prospective Studies
Incidence
Diet
UK Biobank

@article {pmid41915254,
year = {2026},
author = {Fahim, F and Farajzadeh, M and Rahatijafarabad, B and Mohammadi, AM and Khorram, A and Mostafaei, M and Nikbakht, O and Zamiri, R and Sepehrian, N and Oveisi, S and Zali, A},
title = {Deep brain stimulation of the fornix for Alzheimer's disease: A systematic review and meta-analysis of cognitive outcomes.},
journal = {Neurosurgical review},
volume = {49},
number = {1},
pages = {},
pmid = {41915254},
issn = {1437-2320},
}

@article {pmid41915294,
year = {2026},
author = {Farzeen, I and Batool, M and Saeed, S and Mustafa, G and Yasmeen, M and Nazir, MM and Ashraf, A},
title = {Metabolic reprogramming of neurons in alzheimer disease: a biochemical perspective.},
journal = {Metabolic brain disease},
volume = {41},
number = {1},
pages = {},
pmid = {41915294},
issn = {1573-7365},
}

@article {pmid41915305,
year = {2026},
author = {Fukuchi, M and Izumi, H and Sakurai, D and Shinohara, Y and Arimura, K and Saito-Moriya, R and Kitada, N and Huanood, G and Nakasone, H and Maki, SA and Mori, H},
title = {Visualizing Changes in Brain-Derived Neurotrophic Factor Expression in Living Mice Using the All-Engineered Bioluminescence Imaging System AkaBLI.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {41915305},
issn = {1559-1182},
support = {22K11859//Japan Society for the Promotion of Science/ ; },
mesh = {Animals ; *Brain-Derived Neurotrophic Factor/metabolism/genetics ; Mice, Transgenic ; *Luminescent Measurements/methods ; Brain/metabolism ; Mice ; Alzheimer Disease/metabolism ; Disease Models, Animal ; },
abstract = {Brain-derived neurotrophic factor (BDNF) plays a pivotal role in neuronal development, synaptic plasticity, and cognitive function, and its dysregulation is implicated in various neurodegenerative and neuropsychiatric disorders. To noninvasively monitor dynamic changes in Bdnf expression in vivo, we developed a novel transgenic mouse line, Bdnf-AkaLuc transgenic (Tg) mice, in which the coding region of BDNF was replaced in a BAC transgene with a mutant luciferase, AkaLuc. This luciferase is optimized for the synthetic substrate AkaLumine, which emits near-infrared bioluminescence suitable for deep-tissue imaging. This engineered bioluminescence imaging (BLI) system, termed AkaBLI, enables robust and highly sensitive detection of bioluminescence in the brains of living mice, significantly outperforming our previous Bdnf-Luciferase Tg model. Using this system, we successfully visualized activity-dependent Bdnf mRNA induction in response to pilocarpine-induced status epilepticus. To overcome the limitations of repeated imaging, we identified optimal BLI intervals and established a hairless Bdnf-AkaLuc Tg line, facilitating long-term longitudinal monitoring. Furthermore, by crossing Bdnf-AkaLuc Tg mice with 5xFAD Alzheimer's disease model mice, we successfully visualized reductions in Bdnf expression in the brains of living 5xFAD mice. Our study introduces a powerful tool for noninvasive, continuous visualization of Bdnf regulation under both physiological and disease-related conditions. This imaging approach holds potential for advancing our understanding of BDNF-related brain function and for evaluating therapeutic strategies targeting BDNF in neurological disorders.},
}

Animals
*Brain-Derived Neurotrophic Factor/metabolism/genetics
Mice, Transgenic
*Luminescent Measurements/methods
Brain/metabolism
Mice
Alzheimer Disease/metabolism
Disease Models, Animal

@article {pmid41915331,
year = {2026},
author = {Yang, L and Song, G and Parker, E and Yang, L},
title = {Inhaled General Anesthetics in Alzheimer's Disease Progression: Divergent Effects, Underlying Mechanisms, and Future Perspectives.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {41915331},
issn = {1559-1182},
support = {32300959//National Natural Science Foundation of China/ ; SL2024A04J00578//Guangzhou Scientific Research Grant/ ; 22KJ04//SCNU Young Faculty Development Program/ ; },
mesh = {Humans ; *Alzheimer Disease/pathology/drug therapy/metabolism ; *Disease Progression ; Animals ; *Anesthetics, Inhalation/therapeutic use/adverse effects/pharmacology ; *Anesthetics, General/therapeutic use ; Neuroprotective Agents/therapeutic use ; },
abstract = {Alzheimer's disease (AD) is a devastating, age-related neurodegenerative disorder characterized by progressive cognitive decline, neuronal loss, and hallmark pathologies like β-amyloid (Aβ) deposition and tau hyperphosphorylation. With global aging, more AD patients or high-risk individuals undergo perioperative care, exposing them to inhaled anesthetics such as isoflurane and sevoflurane. Preclinical and clinical evidence on these agents' effects on AD pathogenesis remains conflicting, ranging from exacerbating pathology to neuroprotection, highlighting the critical need to clarify the context-dependent effects and mechanisms driving these outcomes. This review synthesizes how inhaled anesthetics interact with core AD pathologies, highlighting the widely used inhaled anesthetics on AD progression, molecular targets, and exposure parameters. Furthermore, we discuss emerging neuroprotective interventions (e.g., antioxidants, trehalose) that mitigate neuronal damage. These findings inform personalized perioperative strategies for AD-susceptible populations, aiming to reduce iatrogenic risks and improve long-term neurological outcomes.},
}

Humans
*Alzheimer Disease/pathology/drug therapy/metabolism
*Disease Progression
Animals
*Anesthetics, Inhalation/therapeutic use/adverse effects/pharmacology
*Anesthetics, General/therapeutic use
Neuroprotective Agents/therapeutic use

@article {pmid41915334,
year = {2026},
author = {Zhang, L and Jia, H and Pan, C and Xu, Z and Liu, S},
title = {The Multifaceted Roles of GPR120 in Central Nervous System Disorders: Mechanistic Insights and Therapeutic Implications.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {41915334},
issn = {1559-1182},
mesh = {Humans ; Animals ; *Receptors, G-Protein-Coupled/metabolism ; *Central Nervous System Diseases/metabolism/therapy/drug therapy ; Signal Transduction ; },
abstract = {G protein-coupled receptor 120 (GPR120), also known as free fatty acid receptor 4 (FFAR4), is a receptor for ω-3 polyunsaturated fatty acids (ω-3 PUFAs), mainly including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). It is widely expressed in the central nervous system on microglia, astrocytes, and neurons, where it regulates neuroinflammation and homeostasis. This review summarizes the mechanism insights and therapeutic potential of GPR120 in neurological and psychiatric disorders. Mechanistic studies indicated that GPR120 activation predominantly engages a β-arrestin2-dependent signaling pathway, which inhibits the TAK1/TAB1 complex, suppresses NF-κB and NLRP3 inflammasome pathways, and thus alleviates neuroinflammation. GPR120 signaling also regulates mitophagy and mitigates endoplasmic reticulum stress, promoting neuronal survival and function. In disease models, GPR120 activation is consistently neuroprotective, reducing seizure severity in epilepsy by inhibiting the NLRP3/caspase-1/IL-1β axis, decreasing pathological deposits in Alzheimer's disease by enhancing Aβ clearance, improving post-ischemic outcomes in stroke via anti-apoptotic and anti-inflammatory mechanisms, and improving behavior in depression models by suppressing microglial M1 polarization and restoring synaptic plasticity. Preclinical studies support the efficacy of selective GPR120 agonists (such as TUG-891, CpdA). However, clinical translation faces major challenges: differences in receptor pharmacology between humans and mice (about 82% sequence homology), weak endogenous ligands, high plasma protein binding (> 99%), and the absence of neurologically focused clinical trials. Future research should focus on addressing species differences, optimizing brain-targeted delivery strategies, and advancing translational studies from preclinical to clinical settings to evaluate the practical application value of GPR120 in central nervous system disorders.},
}

Humans
Animals
*Receptors, G-Protein-Coupled/metabolism
*Central Nervous System Diseases/metabolism/therapy/drug therapy
Signal Transduction

@article {pmid41915395,
year = {2026},
author = {Macedo, AC and de Lima, AG and Miaw, ISL and Bizzi, IH and Balbino, JMV and Therriault, J and Zimmer, ER and Ghezzi, P and Rosa-Neto, P},
title = {Quality Gaps in Online Media Coverage of Antiamyloid Monoclonal Antibodies for Alzheimer Disease.},
journal = {JAMA network open},
volume = {9},
number = {3},
pages = {e265026},
doi = {10.1001/jamanetworkopen.2026.5026},
pmid = {41915395},
issn = {2574-3805},
}

@article {pmid41915524,
year = {2026},
author = {Feng, R and Chen, H and Yao, Y and Wu, L and Liang, T and Xiang, W and Li, J and Loo, CK and Yu, J and Wang, W and Li, J},
title = {Towards Cognitive Impairment Screening in Elderly Communities with Audio-Visual Modal Disentangled Representation Learning.},
journal = {IEEE journal of biomedical and health informatics},
volume = {PP},
number = {},
pages = {},
doi = {10.1109/JBHI.2026.3679693},
pmid = {41915524},
issn = {2168-2208},
abstract = {Alzheimer's disease (AD) is pressing global health concerns, for which early diagnosis is critical to effective intervention. However, conventional approaches, including neuropsychological assessments and neuroimaging techniques, are resource-intensive and impractical for community-level screening. In contrast, artificial intelligence-driven behavioral analyses, including speech pattern and facial expression recognition, have demonstrated considerable potential for scalable and non invasive cognitive assessment. This work presents a community-oriented intelligent screening system for cognitive impairment screening in elderly populations. As a foundation, we introduce CIR-AV, the first large-scale Mandarin-based multimodal dataset for cognitive impairment recognition in Chinese older adults, encompassing 574 community-dwelling participants with comprehensive facial expression and speech data. Building upon this resource, we propose DiVA, a disentangled audio-visual fusion framework that decomposes multimodal features into shared and specific representations. A trajectory constrained mechanism enhances representation purity, while a cross-modal attention-based dynamic fusion (CMF) module adaptively balances modality contributions, ensuring robust performance under real-world conditions. Experimental results demonstrate that DiVA achieves an AUC of 78.66% at the segment level and an accuracy of 79.46% at the subject level, significantly outperforming state-of the-art methods. With its cost-efficient and scalable de sign, it is well-suited for large-scale community screening, providing a practical solution for early dementia detection in resource-limited settings with considerable social and economic value.},
}

@article {pmid41915579,
year = {2026},
author = {Ashchi, A and Lachapelle, AA and Nassirou, S and Huston, J},
title = {Leqembi (Lecanemab) in Early Alzheimer's Disease: A Review of Clinical Trial Evidence and Therapeutic Implications.},
journal = {Reviews on recent clinical trials},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115748871418305260224075827},
pmid = {41915579},
issn = {1876-1038},
abstract = {Lecanemab is an IgG1 monoclonal antibody that has emerged as the first FDAapproved drug to slow the progression of Alzheimer's disease by targeting amyloid plaques, with the potential to serve as a disease-modifying therapy. Ongoing clinical studies are evaluating the efficacy and safety of the medication; however, much of the current literature remains mixed regarding the clinical effectiveness of lecanemab. The results from the Clarity AD study, the largest clinical study regarding the effectiveness of lecanemab to date, revealed a statistically significant 27% reduction in the progression of cognitive decline and favorable secondary endpoints in patients with mild cognitive impairment or mild dementia, particularly in male patients as well as heterozygous APOE4 carriers. However, approximately 21% of participants who received lecanemab treatment developed amyloid-related imaging abnormalities, with a higher incidence in homozygous APOE4 carriers. These findings highlight the need to thoroughly screen patients to confirm amyloid pathology with an amyloid PET scan or CSF biomarkers, and to determine APOE4 status before treatment. Additional barriers to care include the financial cost of the medication as well as the need to administer the drug intravenously at a healthcare facility to ensure proper management. Additional studies must continue to explore the clinical impact and safety of the medication and increase its accessibility. Future research may also include analyzing the utilization of the drug in combination therapies to optimize patient outcomes. This paper aims to provide a comprehensive review of current data on lecanemab, its clinical implications, and potential future directions for the use of lecanemab.},
}

@article {pmid41915835,
year = {2026},
author = {Davi, V and Parutto, P and Zhang, Y and Konno, T and Crapart, C and Pereira, R and Franklin, JP and Awadelkareem, MA and Maddison, DC and Devine, MJ and Gomes, ER and Chambers, J and Koslover, E and Avezov, E},
title = {Endoplasmic Reticulum Geometry Dictates Neuronal Bursting via Calcium Store Refill Rates and Exposes Selective Neuronal Vulnerability.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e21101},
doi = {10.1002/advs.202521101},
pmid = {41915835},
issn = {2198-3844},
support = {UKDRI-2203//UK Dementia Research Institute/ ; /MRC_/Medical Research Council/United Kingdom ; 2034482//NSF/ ; grant AS-525 (AS-PhD 19a-015)//Alzheimer Society/ ; //Evelyn Trust/ ; },
abstract = {The endoplasmic reticulum (ER)'s continuous morphology is tightly controlled by ER-shaping proteins, whose genetic or expression defects drive a spectrum of neurodegenerative disorders from Hereditary Spastic Paraplegia to Alzheimer's disease. Why perturbations in ER morphology manifest specifically in neurons remains unknown. Here, by coupling visualisation of global sub-Hz firing bursts to ER ultrastructural manipulations in human inducible Pluripotent Stem Cells (hiPSC)-derived cortical neurons, alongside physical simulations, we establish a key ER structure-function principle: neuronal ER architecture dictates Ca[2+] replenishment speed. Altering ER structure hinders network ER luminal connectivity and Ca[2+] propagation from refill points at plasma membrane contact sites, impairing the ER's capability to supply repetitive Ca[2+] bursts. The ER morpho-regulatory control of Ca[2+] refill speed thus constitutes a switch on neuronal activity. Further, perturbed ER shape also abolishes Ca[2+] firing and contraction in primary skeletal muscle cells. These results expose the selective vulnerability of Ca[2+]-firing cells to ER structural disruptions, rationalizing ER dysfunction in neurodegeneration and unveiling a new role for the continuous ER morphology that could apply universally to Ca[2+]-firing cells.},
}

@article {pmid41915856,
year = {2026},
author = {Ge, J and Pagnon de la Vega, M and Zampar, S and Cerilli, E and Koutarapu, S and Wu, L and Fraser, P and Arkan, S and Giedraitis, V and Lannfelt, L and Hultqvist, G and Syvänen, S and Ingelsson, M and Hanrieder, J and Sehlin, D},
title = {The Uppsala APP Mutation Promotes Wild-Type Amyloid-β Aggregation and Deposition In Vivo.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e14179},
doi = {10.1002/advs.202514179},
pmid = {41915856},
issn = {2198-3844},
support = {2016-02120//Swedish Research Council/ ; 2018-02715//Swedish Research Council/ ; 2019-02397//Swedish Research Council/ ; 2021-03524//Swedish Research Council/ ; 2023-02796//Swedish Research Council/ ; R01 AG078796/NH/NIH HHS/United States ; R21AG080705/NH/NIH HHS/United States ; PJT-173479//Canadian Institutes for Health Research/ ; AF-1032753//Alzheimerfonden/ ; AF-980959//Alzheimerfonden/ ; FO2025-0126//Hjärnfonden/ ; 253045//Konung Gustaf V:s och Drottning Victorias frimurarestiftelse, Stiftelsen Maja & J.P. Åhlén/ ; 2025-329//Stiftelsen för Gamla Tjänarinnor/ ; //Stohne's Stiftelse and Goljes stiftelse/ ; },
abstract = {Amyloid-β (Aβ) is widely regarded as a key initiator of theneurodegenerative cascade in Alzheimer's disease (AD).Studies of pathogenic mutations in the amyloid precursor protein (APP) genehave greatly advanced understanding of Aβ biochemistry, aggregation, anddeposition. One such mutation, Uppsala APP (APPUpp), produces AβUpp42Δ19-24, whichis highly aggregation-prone due to a six-amino-acid deletion in its central region.In both human APPUpp carriers and the recently developed tg-UppSwe mouse model, Aβ depositspredominantly consist of the human AβUpp mutant.However, whereas human carriers produce both wild-type Aβ (Aβwt) and AβUpp, tg-UppSwe mice express only AβUpp. To better mimic the human condition, weinvestigated the pathological interplay between Aβwt and AβUpp using in vitroco-aggregation assays and in vivo analyses in abitransgenic mouse model generated by crossing tg-UppSwe with tg-Swe mice. ELISA, immunohistochemistry, and MALDI mass spectrometry imaging revealed that earlydeposition of AβUpp42Δ19-24accelerates aggregation and deposition of Aβwt species (Aβwt38, Aβwt40, Aβwt42), likely through a seeding or catalytic mechanism. Notably, bitransgenic mice developed pronounced plaque-associated gliosisan alteration absent in tg-UppSwe animals. These findings suggest a synergistic interaction betweenAβUpp and Aβwt that may influence onset, progression, and structural featuresof Aβ plaques in APPUpp mutation carriers.},
}

@article {pmid41916096,
year = {2026},
author = {Kim, S and Jung, YC and Kim, E and Kim, KY and , },
title = {Right-lateralized cerebellar cortical thickening is associated with mild behavioral impairment in mild cognitive impairment.},
journal = {The journal of prevention of Alzheimer's disease},
volume = {13},
number = {5},
pages = {100540},
doi = {10.1016/j.tjpad.2026.100540},
pmid = {41916096},
issn = {2426-0266},
abstract = {BACKGROUND: Mild Behavioral Impairment (MBI) reflects later-life emergence of persistent neuropsychiatric symptoms and is increasingly recognized as an early manifestation of neurodegenerative disease, yet cerebellar correlates remain underexplored. We tested whether cerebellar morphometry is associated with incident MBI in mild cognitive impairment (MCI).

METHODS: Using longitudinal Alzheimer's Disease Neuroimaging Initiative data, MBI was derived from Neuropsychiatric Inventory/ Neuropsychiatric Inventory-Questionnaire items mapped to five diagnostic domains and defined as new symptoms persisting for ≥2 consecutive visits after a symptom-free baseline. Of 530 MCI participants without baseline symptoms, 181 who developed MBI were matched 1:1 to controls by age, sex, and education. DeepCERES quantified lobular cerebellar cortical thickness and asymmetry from 3T T1-weighted MRI. We used logistic regression with false discovery rate correction and conducted domain-specific analyses (affective dysregulation, impulse dyscontrol, decreased motivation).

RESULTS: MBI cases had lower Mini Mental State Examination scores and higher dementia conversion than controls. Greater thickness in right cerebellar lobules IV (OR 1.215), V (OR 1.122), and VIIIB (OR 1.169), and greater asymmetry in right lobule V (OR 1.035), were associated with incident MBI. Affective dysregulation showed the strongest, largely right-lateralized associations and greater interhemispheric asymmetry. Main results were unchanged after separate sensitivity adjustments for Mini Mental State Examination scores and for index-visit psychiatric medication use.

CONCLUSION: Incident MBI in MCI is linked to right-lateralized cerebellar cortical thickening and asymmetry, most prominently for affective dysregulation. These patterns may reflect early compensatory and/or neuroinflammatory processes within cerebello-cortical circuits relevant to affect regulation.},
}

@article {pmid41916100,
year = {2026},
author = {Gong, H and Liu, J and Wang, Y and Lin, X and Wu, G and Ou, Y and Zhou, M and Yang, L and Peng, J and Ye, X and Wang, Y and Xu, F and Zhou, H and Feng, Z},
title = {Semaglutide treatment reverses HFD induced hippocampal microglia activation and improves cognitive dysfunction.},
journal = {Tissue & cell},
volume = {101},
number = {},
pages = {103495},
doi = {10.1016/j.tice.2026.103495},
pmid = {41916100},
issn = {1532-3072},
abstract = {Long-term high-fat diets (HFD) induce obesity, neuroinflammation, and cognitive decline, increasing Alzheimer's disease (AD) risk. This study explores whether Semaglutide, a GLP-1 receptor agonist, mitigates these effects by modulating microglia via IGFBPL-1 and the PI3K/AKT pathway. In HFD-fed C57/BL6 mice, Semaglutide improved cognitive function, reduced hippocampal microglia activation, and decreased AD-like pathology (phospho-Tau, Aβ). IGFBPL-1, a neuroprotective factor downregulated by HFD and restored by Semaglutide. Direct IGFBPL-1 supplementation replicated Semaglutide's benefits, while PI3K/AKT inhibition blocked them. These findings reveal IGFBPL-1 as a key mediator of Semaglutide's neuroprotection, offering novel insights into combating obesity-linked neurodegeneration.},
}

@article {pmid41916153,
year = {2026},
author = {Wang, C and Xu, X and Zhu, H and Wu, D and Liang, J and Wang, X and Song, R and Shen, L and Hu, Y and Wang, D and Zhu, H and Cheng, X and Qi, Y},
title = {Acori tatarinowii Rhizoma-Curcumae Radix herbal pair ameliorates cognitive impairment and suppresses neuro-inflammation via Ca[2+]/CaMKKβ/AMPK/mTOR pathway in Alzheimer's disease.},
journal = {Journal of ethnopharmacology},
volume = {365},
number = {},
pages = {121606},
doi = {10.1016/j.jep.2026.121606},
pmid = {41916153},
issn = {1872-7573},
abstract = {Effective activation of neuronal autophagy and clearance of amyloid-beta (Aβ) represents a promising therapeutic strategy in the treatment of Alzheimer's disease (AD). The Acori Tatarinowii Rhizoma-Curcumae Radix Herbal pair (ACHP), derived from the traditional Changpu Yujin Decoction, has a long history in Traditional Chinese Medicine for addressing conditions related to cognitive function. However, the precise mechanisms underlying its role in autophagic dysfunction-related dementia remain unclear.

AIM OF THE STUDY: This study aims to investigate the neuroprotective effects of ACHP and the underlying mechanisms in AD.

MATERIALS AND METHODS: Analysis of prototype constituents in drug-containing serum was performed using UHPLC-Triple-TOF/MS. The neuroprotective effects of ACHP were evaluated in APP/PS1 mice using behavioral tests, including the Y-maze and Morris water maze. Transcriptomic analysis was conducted to identify potential neuroprotective pathways activated by ACHP. Neuronal damage and structural recovery were assessed through HE and Nissl staining. In addition, the anti-inflammatory and autophagy-regulating effects of ACHP were further investigated in N2a/APP cells. The molecular mechanisms were further elucidated using Western blot, immunofluorescence, ELISA, and qRT-PCR in both in vivo and in vitro models.

RESULTS: Twenty-five compounds in ACHP-treated mouse serum were identified. ACHP improved spatial learning and memory performance, increased intracellular Ca[2+] levels and downregulated the expressions of proinflammatory cytokines, including TNF-α, IL-1β, and IL-6, while significantly promoting autophagy. ACHP increased CaMKKβ protein expression and activated the AMPK signaling pathway (elevated p-AMPK/AMPK ratio), as well as those of autophagy-related proteins, while improving neuronal morphology.

CONCLUSION: These findings indicate that ACHP alleviates neuro-inflammatory damage and cognitive impairment potentially through modulation of the Ca[2+]/CaMKKβ-AMPK-mTOR signaling pathway involved in autophagy.},
}

@article {pmid41916202,
year = {2026},
author = {Musrah, ATS and Nugraha, DY and Kumfor, F and Piguet, O},
title = {Unravelling cognition-Emotion mechanisms in Alzheimer's disease and frontotemporal dementia: A network analysis approach.},
journal = {Cortex; a journal devoted to the study of the nervous system and behavior},
volume = {199},
number = {},
pages = {60-82},
doi = {10.1016/j.cortex.2026.03.009},
pmid = {41916202},
issn = {1973-8102},
abstract = {Emotion processing deficits are common in Alzheimer's disease (AD) and behavioural-variant frontotemporal dementia (bvFTD), yet few studies have examined how specific cognitive domains relate to emotion processing in these syndromes. This study investigated these relationships using network psychometrics. A total of 209 participants (56 AD, 55 bvFTD, 98 healthy controls) completed neuropsychological testing. Cognitive functions were assessed with the Addenbrooke's Cognitive Examination-III and the Sydney Language Battery, while emotion processing was measured with the Facial Affect Selection Task. Network models were estimated for each group and compared using the Network Comparison Test (NCT). Both patient groups showed impaired emotion recognition versus controls. Network density was highest in bvFTD (.62), followed by AD (.44), with controls showing the sparsest network (.16). In AD, emotion processing was associated with semantic comprehension and semantic knowledge, whereas in bvFTD, emotion processing related more closely to verbal fluency. Centrality indices supported these syndrome-specific patterns. NCT results showed no significant global differences in overall strength (St = .55, p = .411) or structure (Mt = .34, p = .529) between AD and bvFTD networks, indicating comparable overall organization despite differing functional roles of specific nodes. These findings suggest disease-specific cognitive-emotion associations: semantic mechanisms in AD and fluency-related mechanisms in bvFTD. Importantly, however, contributions of other cognitive processes, not measured here, are also plausible. Overall, the study highlights both shared and distinct patterns characterizing emotion processing impairments across dementias, offering insights for developing tailored interventions targeting syndrome-specific cognitive profiles.},
}

@article {pmid41916281,
year = {2026},
author = {Ellingford, R and Harris, SS and Kehring, M and Rajani, RM and Lam, FKW and Graykowski, D and Bӧken, D and Welikovitch, LA and Khasnavis, A and Laban, R and Heslegrave, A and Yaman, U and Mate de Gerando, A and Bond, SA and Wray, S and Salih, DA and Dupret, D and Dolan, RJ and Klenerman, D and Zetterberg, H and Hyman, BT and Busche, MA},
title = {Alzheimer's disease pathology degrades an NMDA receptor-dependent spontaneous activity pattern in cortico-hippocampal circuits.},
journal = {Neuron},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neuron.2026.02.027},
pmid = {41916281},
issn = {1097-4199},
abstract = {Memory-based cognition relies on the integrity of cortico-hippocampal circuits, which are compromised in Alzheimer's disease (AD) as β-amyloid (Aβ) and tau accumulate. However, the mechanisms linking this pathology to circuit dysfunction remain unclear. In mouse models, using in vivo two-photon and Neuropixels recordings, we show that Aβ-tau pathology promotes both region- and layer-specific impairments, involving reduced burst firing in superficial cortical layers and CA1 and reduced mean firing of excitatory and inhibitory neurons in deep cortical layers and CA1. Exposure to Aβ primed the susceptibility of neuronal populations to tau-induced impairment. Combined Aβ-tau reduced synaptic NMDA receptor (NMDAR) density in both mouse and human tissue, while Aβ-tau co-reduction restored NMDARs and firing patterns and improved contextual memory. NMDAR antagonism in healthy mice phenocopied regional and laminar deficits. Our findings implicate synaptic NMDAR hypofunction as a reversible mechanism linking Aβ-tau synergy to cortico-hippocampal dysfunction in AD.},
}

@article {pmid41916283,
year = {2026},
author = {Ali, M and Timsina, J and Xu, Y and Chen, Y and Gong, K and Western, D and Heo, G and Liu, M and Budde, J and Pottier, C and Schindler, SE and Morris, JC and Holtzman, DM and Puerta, R and Cano, A and Boada, M and Fernandez, MV and Ruiz, A and Aguilar, M and Alvarez, I and Pastor, P and Perlmutter, JS and Campbell, MC and Kotzbauer, PT and Oh, HS and Wilson, EN and Guen, YL and , and , and , and , and , and , and Tarawneh, R and Wyss-Coray, T and Sung, YJ and Ibanez, L and Cruchaga, C},
title = {Large-scale CSF and plasma proteomics reveal immune, synaptic, and extracellular matrix disruptions across neurodegenerative diseases.},
journal = {Neuron},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neuron.2026.02.035},
pmid = {41916283},
issn = {1097-4199},
abstract = {Neurodegenerative diseases (NDs), including Alzheimer's disease (AD), Parkinson's disease (PD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD), share overlapping clinical and pathological features. We analyzed cerebrospinal fluid (CSF) and plasma proteomes from 2,705 and 3,009 samples, respectively, across these NDs, identifying disease-specific and shared molecular signatures. CSF showed more disease-associated proteins than plasma, with AD and DLB exhibiting the strongest cross-tissue similarity. Pathway analyses revealed shared dysregulation of immune-related processes in CSF and plasma across the NDs, as well as disease-specific impairment of glycosylation and apoptotic pathways in AD; ATF4 and PERK signaling in PD; fibroblast growth factor receptor (FGFR) and interleukin signaling in DLB; and glycoprotein hormones disruption in FTD. We developed disease-specific predictive models showing high accuracy (area under the curve [AUC]: 0.81-0.95 in CSF and 0.80-0.89 in plasma). These findings reveal distinct and convergent mechanisms across NDs, highlighting potential biomarkers and pathways for diagnostic and therapeutic strategies in neurodegeneration.},
}

@article {pmid41916306,
year = {2026},
author = {Hebisch, M and Kamin, V and Cenini, G and Piazzesi, A and Bertan, F and Weykopf, B and Schlee, J and Kaniyappan, S and Washicosky, KJ and Kim, DY and Bano, D and Peitz, M and Brüstle, O},
title = {Recapitulation of plaque formation, tau pathology, and neurodegeneration in a human 3D matrix model of Alzheimer's disease.},
journal = {Cell reports methods},
volume = {},
number = {},
pages = {101365},
doi = {10.1016/j.crmeth.2026.101365},
pmid = {41916306},
issn = {2667-2375},
abstract = {This study aims at implementing a 3D cell culture model of Alzheimer's disease (AD). To that end we engineered human induced pluripotent stem cell (iPSC)-derived neural stem cells to conditionally overexpress FAD mutant APP and PSEN1 variants. After differentiation in 3D basement membrane matrices, cultures exhibited increased Aβ42 and Aβ40 levels and a highly pathogenic shift of the Aβ42/40 ratio. Typical AD phenotypes such as amyloid deposition and tau pathology were observed alongside impaired mitochondrial integrity and neuronal damage. Pathophenotypes were ameliorated by γ-secretase inhibition, confirming amyloid toxicity as main driver of AD pathology. iPSC-derived microglia added to the cultures engulfed Aβ and apoptotic cells, underscoring the modularity of this experimental system. We expect our model to provide a useful tool for assessing the impact of amyloid reduction on downstream AD pathologies such as mitochondrial dysfunction, neuroinflammation, and neurodegeneration, in particular in light of recent progress in the development and use of amyloid-targeting drugs.},
}

@article {pmid41916355,
year = {2026},
author = {Medoro, A and Foderà, E and Ronci, M and Trerotola, M and Mignogna, D and Raimo, G and Intrieri, M and De Martino, A and Lepore, A and Porcile, C and Benincasa, T and Russo, C and Passarella, D},
title = {Generation and validation of C-terminal LRP8 antibodies for detecting processed intracellular fragments.},
journal = {BioTechniques},
volume = {78},
number = {1-12},
pages = {111-122},
doi = {10.1080/07366205.2026.2645347},
pmid = {41916355},
issn = {1940-9818},
mesh = {Humans ; *LDL-Receptor Related Proteins/immunology/metabolism/analysis/chemistry ; Reelin Protein ; Animals ; Mice ; Antibodies, Monoclonal/immunology ; *Antibodies/immunology ; Alzheimer Disease/metabolism ; Immunohistochemistry/methods ; },
abstract = {Introduction: Low-density lipoprotein receptor-related protein 8 (LRP8) is a neuronal receptor for apolipoprotein E and Reelin, two ligands critically involved in Alzheimer's disease (AD), neuronal migration, and memory. Because LRP8 is highly expressed in neurons, interacts with amyloid precursor protein, and undergoes γ-secretase-dependent processing, it has emerged as a potential contributor to AD-related neurodegeneration. Growing evidence also implicates LRP8 in carcinogenesis, highlighting the need to better define its molecular properties. Areas covered: This article addresses the limited understanding of LRP8 proteolytic processing, cellular localization, and molecular interactions, due in part to the lack of suitable antibodies. We present and characterize novel polyclonal and monoclonal antibodies directed against the C-terminal region of LRP8, suitable for Western blotting and immunocytochemistry/immunofluorescence. These reagents enabled detection of a previously unrecognized intracellular low-molecular-weight (∼12 kDa) C-terminal LRP8 fragment. Expert opinion/Commentary: These antibodies provide valuable new tools for mechanistic studies of LRP8. By improving the investigation of LRP8 processing and localization, they may facilitate a better understanding of its role in neurodegeneration and cancer.},
}

Humans
*LDL-Receptor Related Proteins/immunology/metabolism/analysis/chemistry
Reelin Protein
Animals
Mice
Antibodies, Monoclonal/immunology
*Antibodies/immunology
Alzheimer Disease/metabolism
Immunohistochemistry/methods

@article {pmid41916432,
year = {2026},
author = {Liu, H and Zhong, XC and Xiong, J and Zhou, L and Zeng, SQ and Wang, HB and Li, ZQ},
title = {Efficacy and acupoint specificity of sedative-tranquilizing acupuncture for Alzheimer's disease with sleep disorders: a three-arm randomized controlled trial protocol.},
journal = {Complementary therapies in medicine},
volume = {},
number = {},
pages = {103366},
doi = {10.1016/j.ctim.2026.103366},
pmid = {41916432},
issn = {1873-6963},
abstract = {OBJECTIVES: Sleep disorders (SD) are highly prevalent in patients with Alzheimer's disease (AD); however, effective pharmacological interventions are often limited by adverse effects or insufficient efficacy. This study aims to evaluate the clinical synergistic value and the "sleep-cognition co-modulation" effect of sedative-tranquilizing acupuncture, a specialized non-pharmacological therapy, in managing AD-SD comorbidity.

PARTICIPANTS AND METHODS: This is a multicenter, randomized, controlled trial (RCT) involving 72 participants diagnosed with both AD and SD. Participants will be randomly assigned (1:1:1) to one of three groups: the control group, receiving standard care (donepezil hydrochloride combined with cognitive behavioral therapy for insomnia [CBT-I]); the acupuncture group, receiving sedative-tranquilizing acupuncture in addition to standard care; and the sham acupuncture group, receiving sham acupuncture plus standard care. The primary outcome measure is the change from baseline in the Pittsburgh Sleep Quality Index (PSQI) score. Secondary outcomes include cognitive function (Mini-Mental State Examination [MMSE]), quality of life (Quality of Life in Alzheimer's Disease [AD-QOL] scale), and psychological symptoms (Hamilton Anxiety Scale [HAMA] and the 17-item Hamilton Depression Scale [HAMD-17]). Furthermore, peripheral biochemical markers, polysomnography (PSG) parameters, and neuroimaging data will be analyzed to explore underlying mechanisms. All analyses will be performed on an intention-to-treat (ITT) basis.

CONCLUSIONS: This trial is expected to provide robust clinical evidence regarding whether sedative-tranquilizing acupuncture can effectively assist in improving sleep quality and cognitive function in patients with AD-SD comorbidity. The findings will further elucidate the potential neurobiological mechanisms of acupuncture and offer a novel integrative strategy for the management of AD-related sleep disturbances.

TRIAL REGISTRATION: This protocol was approved by the Ethics Committee of Nanchang Hongdu Hospital of Traditional Chinese Medicine (KYKS-2024044-1(X-2) and registered with the International Traditional Medicine Clinical Trial Registry (https://itmctr.ccebtcm.org.cn/mgt/project/user/user-project-view/09DB9DBC-F576-4AF9-AF4E-D6D88E1B1B6B).},
}

@article {pmid41916755,
year = {2026},
author = {Luthra, NS and Bonham, LW and Moreno, AJ and Park, C and Huguenard, CJC and Abdulai-Saiku, S and Gupta, S and Lin, J and Broestl, L and Bétourné, A and Sehgal, R and Wang, D and Lesné, SE and Ostrem, JL and Yokoyama, JS and Dubal, DB},
title = {Longevity factor klotho and resistance to cognitive deficits in individuals with Parkinson's disease and in an α-synuclein mouse model.},
journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1523/JNEUROSCI.1904-25.2026},
pmid = {41916755},
issn = {1529-2401},
abstract = {Aging is the primary risk factor for Parkinson's disease (PD) and PD-related cognitive impairment remains a major unmet biomedical challenge. Klotho, a pleiotropic protein, extends lifespan and enhances cognition, but whether it confers resilience to cognitive impairments in PD is unclear. Here, we show that in humans, the KL-VS genetic variant of KLOTHO, linked to higher circulating klotho levels, associated with better executive cognition in individuals with PD across two independent cohorts. To test causality and explore mechanisms, we turned to mouse models. Transgenic elevation of klotho in a mouse model increased lifespan, improved synaptic and cognitive, but not motor, functions in mice, and decreased steady state α-synuclein (α-syn) levels in the brains of male mice expressing wildtype human α-syn. Complementary in vitro studies showed that klotho rescued α-syn-induced deficits in NMDAR-dependent signaling through GluN2B and augmented α-syn microglial-related uptake, suggesting a potential mechanism by which klotho counters PD-related toxicity. Together, these findings indicate that klotho can counteract cognitive deficits related to PD, possibly by modulating α-syn levels - and these findings may be relevant to new therapeutic pathways for PD.Significance statement Klotho is a longevity factor that improves cognition in old mice, Alzheimer's disease model mice, and old nonhuman primates, yet its role Parkinson's disease (PD)-related cognitive impairment remains unclear. Here, we identified an association between a KLOTHO variant and executive cognitive function in PD, a cognitive domain preferentially affected by the disease. To investigate biological mechanisms of klotho, we leveraged an α-synuclein mouse model of PD and found that klotho decreased cognitive deficits, potentially by increasing synaptic plasticity and reducing α-synuclein levels. Together, these findings suggest that klotho modulates PD-related cognitive deficits and highlight klotho-based strategies as promising therapeutic pathways for cognitive impairment in PD and other α-synucleinopathies.},
}

@article {pmid41916866,
year = {2026},
author = {Chen, C and Zhou, M and Tang, L},
title = {Comment on "Alzheimer's disease diagnosis: An update and review of biomarkers, positron emission tomography, and emerging therapies".},
journal = {Journal of the Formosan Medical Association = Taiwan yi zhi},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jfma.2026.03.102},
pmid = {41916866},
issn = {0929-6646},
}

@article {pmid41916957,
year = {2026},
author = {Raulin, AC and Alnobani, A and Rodriguez-Martinez, P and Lee, E and Linares, C and Yslas, AR and Li, M and Ren, Y and Doss, SV and Roy, B and Kuchenbecker, LA and Martens, YA and Liu, CC and Bu, G and Kanekiyo, T},
title = {Astrocytic APOE3-Christchurch expression ameliorates brain amyloid-β pathology in 5xFAD mice.},
journal = {Translational psychiatry},
volume = {16},
number = {1},
pages = {},
pmid = {41916957},
issn = {2158-3188},
support = {U19AG069701//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; R01AG071226//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; R01AG068034//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; R01AG057181//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; RF1AG081203//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; A2021015F//BrightFocus Foundation (BrightFocus)/ ; },
mesh = {Animals ; *Astrocytes/metabolism ; *Alzheimer Disease/genetics/pathology/metabolism ; *Amyloid beta-Peptides/metabolism ; Mice ; Mice, Transgenic ; Disease Models, Animal ; *Brain/metabolism/pathology ; *Apolipoprotein E3/genetics/metabolism ; Plaque, Amyloid/pathology/metabolism ; Humans ; },
abstract = {The rare APOE3-Christchurch (APOE3Ch) variant is linked to resistance against PSEN1 p.E280A-driven autosomal dominant Alzheimer's disease (AD). Recent studies in AD mouse models have demonstrated an effect of APOE3Ch in reducing tau pathology and tau propagation, yet its effects on amyloid pathology and related toxicity are not fully understood. While prior studies have reported reduced amyloid pathology with APOE3Ch, we extended this knowledge by investigating how astrocyte-specific expression of APOE3Ch impacts amyloid pathology and related responses in 5xFAD mice, an amyloid mouse model. Using adeno-associated virus (AAV)-mediated gene delivery, we overexpressed APOE3 or APOE3Ch in astrocytes of 5xFAD mice at the neonatal stage, then analyzed their effects during the advanced stage of amyloid pathology. Astrocytic APOE expression significantly reduced amyloid burden, neuritic dystrophy, and gliosis compared to GFP controls. Notably, astrocytic APOE3Ch expression, relative to APOE3, markedly lowered oligomeric Aβ levels and promoted the formation of more compact, fibrillar plaques, suggesting a shift toward a less toxic aggregation profile. Transcriptomic profiling of cortical tissue revealed broad downregulation of immune-related and proteostatic pathways. These findings indicate that astrocytic APOE3Ch sufficiently attenuates Aβ pathology and related toxicity, supporting its potential as a therapeutic modifier for AD.},
}

Animals
*Astrocytes/metabolism
*Alzheimer Disease/genetics/pathology/metabolism
*Amyloid beta-Peptides/metabolism
Mice
Mice, Transgenic
Disease Models, Animal
*Brain/metabolism/pathology
*Apolipoprotein E3/genetics/metabolism
Plaque, Amyloid/pathology/metabolism
Humans

@article {pmid41916976,
year = {2026},
author = {Parent, O and Alasmar, Z and Osborne, S and Bussy, A and Costantino, M and Fouquet, JP and Quesada, D and Pastor-Bernier, A and Fajardo-Valdez, A and Pichet-Binette, A and McQuarrie, A and Maranzano, J and Devenyi, GA and Steele, CJ and Villeneuve, S and , and , and Dadar, M and Chakravarty, MM},
title = {Characterizing spatiotemporal white matter hyperintensity pathophysiology in vivo to disentangle vascular and neurodegenerative contributions.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-70832-2},
pmid = {41916976},
issn = {2041-1723},
abstract = {White matter hyperintensities (WMHs) are neuroimaging markers widely interpreted as caused by cerebral small vessel disease, yet emerging evidence suggests that a subset may have a neurodegenerative etiology. Current imaging methods have lacked the specificity to disentangle biological processes underlying WMHs in vivo. Here, we used voxel-level normative modeling and seven microstructural MRI markers with complementary biophysical sensitivities to generate single-subject high-resolution WMH pathophysiology maps in a large cohort (n = 32,526). We calculated data-driven spatial patterns of similar WMHs, revealing distinct periventricular, posterior, and anterior clusters. We identified a reproducible WMH signature linked to dementia and Alzheimer's disease, characterized by a posterior predominance and a pathophysiological pattern indicative of selective fiber degeneration. Posterior WMHs connected cortical regions vulnerable to tau pathology. Our framework helps parsing vascular and neurodegenerative contributions of WMHs in vivo, which could alter the course of treatment strategies and provide nuanced interpretations of research findings.},
}

@article {pmid41917225,
year = {2026},
author = {Bonuck, K and Gao, Q and Congdon, S and Kim, RS},
title = {Long COVID disability burden in US adults.},
journal = {Communications medicine},
volume = {6},
number = {1},
pages = {},
pmid = {41917225},
issn = {2730-664X},
abstract = {BACKGROUND: Five years since the scientific and patient communities first identified the syndrome now known as Long COVID, affected individuals lack treatments, and the US lacks population-based data on its disability burden and correlation with National Institutes of Health (NIH) funding. Moreover, akin to other debilitating conditions it often co-occurs with, e.g., Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and dysautonomia, Long COVID disproportionately impacts females whose concerns are often marginalized.

METHODS: We quantify Long COVID years lived with disability (YLDs= prevalence x disability weight) in US adults and its actual/YLD-commensurate average annual NIH FY2022-2024 funding versus 68 comparator conditions, by sex predominance. We derive Long COVID prevalence from Census Bureau surveys (9/2022-8/2023) and apply disability weights from the Global Burden of Disease Study.

RESULTS: Long COVID YLDs approximate those of Alzheimer's and Asthma. Long COVID received 14% of its disability commensurate funding: $106 million vs. $739.8 million. ME/CFS is the most under-funded condition, receiving <1% of its YLD proportionate funding. Among conditions analyzed, 24 are female-predominant (we estimate Long COVID funding two ways), 12 male-predominant, and 33 show no sex predominance. Among the 12 below-median funded/above-median YLD conditions, 7/12 are female-predominant, none are male-predominant. Median funding/per YLD is 5.2 times higher for male- vs. female-predominant conditions (7.0 vs 1.3 million per YLD, p = 0.007). Overall, YLDs explain 6.5% of funding variance in a linear regression model using YLD as the sole predictor (Adjusted R-squared: 0.065).

CONCLUSIONS: With chronic conditions like Long COVID rising, disability burden merits greater consideration in funding decisions, as does biological sex.},
}