@article {pmid41673649,
year = {2026},
author = {Toussaint, A and Singh, M and Chiou, H and Wang, G and Jia, D and Driscoll, M and Bhatt, V and Ndong, JC and Shuaib, S and Zoltowski, H and Gilleran, J and Peng, Y and Tsymbal, A and Roberge, J and Guo, JY and Herranz, D and Langenfeld, J},
title = {Bone morphogenetic protein receptor 2 signaling mediates mitochondrial Ca[2+] transport through its regulation of TAK1 splice variant.},
journal = {Cell communication and signaling : CCS},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12964-025-02609-x},
pmid = {41673649},
issn = {1478-811X},
support = {R01 CA225830/NH/NIH HHS/United States ; },
abstract = {BACKGROUND: Bone morphogenetic proteins (BMPs) are highly conserved multifunctional signaling proteins with pleotropic effects throughout embryonic development. BMPs are aberrantly expressed in many diseases including cancer and Alzheimer's disease. Recent studies suggested that BMP signaling negatively regulates mitochondrial bioenergetics. The mechanisms by which BMP signaling regulates bioenergetics and cell survival are not known.

METHODS: We utilized BMP type 2 receptor (BMPR2) inhibitor (JL189), BMPR2 kinase domain KO, BMPR2 siRNA, and BMP loss of function mutants in C. elegans to inhibit BMP signaling (BMPR2i). The effects of BMPR2i on mitochondrial bioenergetics were examined by measuring differences in TCA cycle intermediates (mass spectrometer), mitochondrial respiration (Agilent Seahorse), and mitochondrial mass (MitoTracker Green/TFAM). Fluorescent mitochondrial Ca[2+] sensors Rhod-2AM and LAR-GECO were used to detect changes in mitochondrial Ca[2+] levels in cell culture and C elegans respectively. The KO and siRNA of the mitochondria uniporter (MCU) were used to determine the mechanisms BMPR2i regulates the uptake of Ca[2+] into the mitochondria. We compared the responses of BMPR2i in non-small cell lung cancer (NSCLC) cell lines, leukemia cells, breast cancer cells, and HT-22 mouse hippocampal cells to assess whether the biological response varied depending on the cell type.

RESULTS: BMPR2i increased mitochondrial Ca[2+] (mtCa[2+]) levels in all cells lines and in C. elegans, suggesting its regulation of Ca[2+] transport is conserved. BMPR2i induced increase in mtCa[2+] levels were dependent on the MCU, which effected mitochondrial bioenergetics and cell survival. In addition, our data suggests that BMPR2 regulation of mtCa[2+] transport is mediated by TAK1-d splice variant. In leukemia cells, BMPR2i induced significant cell death that was attenuated by MCU KO. In NSCLC and HT-22 cells, BMPR2i increased mitochondrial bioenergetics and induced minimal cell death.

CONCLUSION: These studies reveal that BMPR2 signaling regulates TAK1-d splice variant to mediate mitochondrial Ca[2+] transport, which is dependent on the MCU. Our studies suggest that BMPR2 signaling utilizes mtCa[2+] transport to regulate both mitochondrial bioenergetics and/or cell survival. Our studies provide novel insight into how aberrant BMPR2 signaling is pathogenic and suggests that the response could vary depending on the cell type.},
}

@article {pmid41673623,
year = {2026},
author = {Zhang, Y and Sun, L and Zhao, Y and Zhang, Z and Chen, H and Zhao, M and Miao, Z and Wang, W and Xu, X and , },
title = {Association of soluble tumor necrosis factor receptor 1 with tau pathology, brain atrophy, and cognitive decline: a longitudinal study.},
journal = {BMC medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12916-026-04623-3},
pmid = {41673623},
issn = {1741-7015},
support = {82071511//National Science Foundation of China/ ; },
abstract = {BACKGROUND: We tested whether inflammation indexed by soluble tumor necrosis factor receptor-1 (sTNFR1) is related to cognitive decline. We examined serum sTNFR1 with cognition in the Health and Retirement Study (HRS) and cerebrospinal fluid (CSF) sTNFR1 with tau pathology and magnetic resonance imaging (MRI)-based atrophy in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Finally, we used Mendelian randomization (MR) to assess associations between genetically proxied sTNFR1 and regional brain volumes.

METHODS: Data were from HRS (2016-2020; N = 6028) and ADNI (N = 287). In HRS, serum sTNFR1 was log-transformed (quartiles); in ADNI, CSF sTNFR1 was analyzed. Global cognition included word recall, serial 7 s, and counting backwards. In ADNI, cognition was measured by the Clinical Dementia Rating-Sum of Boxes (CDR-SB); CSF total tau/phosphorylated tau and longitudinal MRI regional volumes were analyzed. Associations were estimated with linear and linear mixed-effects models adjusted for demographic, clinical, and genetic covariates including apolipoprotein E ε4 (APOE ε4). Incident mild cognitive impairment (MCI)/dementia was modeled with cause-specific Cox and Fine-Gray models. Incremental prediction used optimism-corrected change in area under the curve (AUC; ΔAUC), net reclassification improvement (NRI)/integrated discrimination improvement (IDI), calibration, and decision curve analysis. MR used genome-wide association study (GWAS) statistics to test effects of genetically proxied sTNFR1 on MRI-derived regional volumes.

RESULTS: In HRS (follow-up 4 years), higher serum sTNFR1 was associated with lower baseline cognition and faster decline in global cognition (β = - 0.16/year). Higher sTNFR1 predicted MCI/dementia (Cox HR ≈ 1.17; Fine-Gray sHR ≈ 1.14); among cognitively normal individuals, risk was elevated (OR = 1.30; 95% CI, 1.03-1.63). Adding sTNFR1 to 2- and 4-year prediction models conferred small discrimination gains after internal validation (ΔAUC ≤ 0.003) and minimal or inconsistent net clinical benefit. In ADNI, higher CSF sTNFR1 was associated with greater CSF total tau and phosphorylated tau, and predicted accelerated caudate atrophy. Exploratory MR suggested a nominal association with reduced right inferior temporal volume, limited by instruments.

CONCLUSIONS: sTNFR1 is associated with cognitive decline and tau-related selective neurodegeneration, but provides limited incremental predictive value beyond established risk factors; external validation and replication are warranted.},
}

@article {pmid41673538,
year = {2026},
author = {Li, W and Hu, X and Zhang, Y and Liao, J and Lin, S and Chen, X and Lan, H and Zhao, H and Xu, H},
title = {Oral Pain and Alzheimer's Disease: Prospective Cohort and Cross-Sectional Analyses.},
journal = {Journal of dental research},
volume = {},
number = {},
pages = {220345251412305},
doi = {10.1177/00220345251412305},
pmid = {41673538},
issn = {1544-0591},
abstract = {Given the limited effectiveness of Alzheimer's disease (AD) treatments, modifiable risk factors warrant attention. Oral pain (OP), a common inflammatory symptom, may be linked to neurodegeneration. This study aimed to investigate associations between OP and AD risk, cognitive performance, and brain structure. Data from 490,035 UK Biobank participants free of AD at baseline and with complete OP records were analyzed, while other dementias were excluded. Participants were categorized into an OP group (n = 33,697; defined as self-reported toothache or painful gums via touchscreen questionnaire) and an oral pain-free group (n = 456,338). AD diagnoses were ascertained using ICD-10 codes from linked electronic health records and analyzed in a cohort design using multivariable Cox proportional hazards models. A cross-sectional analysis method of cognitive and brain outcomes was performed using multivariable generalized linear models. Over an average follow-up period of 14.1 ± 1.7 y, OP was associated with a 30.7% increased risk of AD (hazard ratio [HR] = 1.307, 95% confidence interval [CI]: 1.165 to 1.466, P < 0.001). Individuals with OP also demonstrated poorer cognitive functions and reduced gray matter volumes in the left parahippocampal gyrus (Padj = 0.014, β = -27.383, SE = 7.728). Among those whose oral pain resolved, the occurrence of AD was lower (HR = 0.360, 95% CI: 0.197 to 0.660, P = 0.011), along with improved cognitive functions and brain structures as compared with those with persistent OP. Proteomic analyses identified potential mediators, including GDF15, BCAN, and PLAUR, which are involved in pathways related to wound healing and immune regulation. Emerging evidence suggested a possible association between OP and AD through neuroimmune pathways, including potential Tau-related changes in the hippocampus. These findings suggested a potential association between maintaining oral health and reduced risk of AD and cognitive impairment. This study addresses a critical gap in understanding how OP may associate with the development of AD.},
}

@article {pmid41673497,
year = {2026},
author = {Shulman, M and Wu, S and Ziogas, N and Edwards, A and Collins, J and Lin, L and Tien, I and Curiale, G and Li, Y and Mummery, C and Lane, R and Junge, C and Beaver, J and Tian, Y and Landen, J and Bullain, S and Gallagher, D},
title = {Exploratory analyses of clinical outcomes from the BIIB080 phase 1b study in mild Alzheimer's disease.},
journal = {Nature aging},
volume = {},
number = {},
pages = {},
pmid = {41673497},
issn = {2662-8465},
abstract = {This study conducted exploratory analyses of the effects of BIIB080, a MAPT (microtubule-associated protein tau)-targeting antisense oligonucleotide, in participants with mild Alzheimer's disease. A multicenter, randomized, double-blind, phase 1b trial was conducted as a placebo-controlled, multiple-ascending dose (MAD) study followed by an open-label, long-term extension (LTE). During the MAD study, participants were randomized and received either intrathecal placebo or BIIB080 10 mg (n = 6), 30 mg (n = 6) or 60 mg (n = 9) every 4 weeks or 115 mg (n = 13) every 12 weeks (Q12W). During the LTE, participants received high-dose BIIB080 (60 mg (n = 7) or 115 mg (n = 9) Q12W). BIIB080 was generally well tolerated. Here we present findings from exploratory analyses, which showed a consistent trend of slowed decline on cognitive, functional and global measures favoring BIIB080 high-dose groups at the end of both study periods. This favorable trend is supported by reported reductions from baseline in brain neurofibrillary tangles measured with tau positron emission tomography. Trial registration: ClinicalTrials.gov identifier: NCT03186989 .},
}

@article {pmid41673459,
year = {2026},
author = {Monnaka, VU and Shipley, B and Boyko, S and de Carvalho Aguiar, PM and Hinczewski, M and Surewicz, WK},
title = {Scaffold-client behavior and structural organization in multicomponent protein condensates as revealed by studying tau/TDP-43 droplets.},
journal = {Communications chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1038/s42004-026-01933-8},
pmid = {41673459},
issn = {2399-3669},
support = {R21 AG094047/AG/NIA NIH HHS/United States ; },
abstract = {Liquid-liquid phase separation (LLPS) is known to modulate pathological aggregation of proteins implicated in neurodegenerative diseases, such as tau and TDP-43. While LLPS mechanisms of individual proteins are well characterized, much less is known about phase behavior of multicomponent protein systems. Here, we investigated the LLPS behavior of mixtures of tau and TDP-43 low complexity domain (LCD), two proteins known to co-aggregate in Alzheimer's disease. We found that, depending on the concentration, each protein can function either as a scaffold (driving condensate formation) or as a client (passively recruited into condensates formed by the other). Notably, scaffold-client roles can be modulated by selectively inhibiting the interactions driving LLPS: electrostatic for tau, and hydrophobic for TDP-43 LCD. A striking feature of this system is the formation of a tau "halo" around TDP-43 LCD droplets, which coarse-grained simulations reveal to arise from tau's amphiphilic organization at condensate interfaces. Together, these findings provide molecular-level insights into the general principles governing the assembly and organization of multicomponent protein condensates.},
}

@article {pmid41673311,
year = {2026},
author = {},
title = {Capillary blood sampling for detecting biomarkers of Alzheimer's disease.},
journal = {Nature medicine},
volume = {},
number = {},
pages = {},
pmid = {41673311},
issn = {1546-170X},
}

@article {pmid41673254,
year = {2026},
author = {Nazli, D and Ipekgil, D and Poyraz, YK and Can, K and Okmen, I and Turhanlar-Sahin, E and Sert Serdar, B and Kocturk, S and Ozhan, G},
title = {Epigallocatechin Gallate and Punicalagin Combination Reduces Aβ Aggregation and Promotes Neurogenesis in Adult Zebrafish Brain.},
journal = {Journal of neuroscience research},
volume = {104},
number = {2},
pages = {e70119},
doi = {10.1002/jnr.70119},
pmid = {41673254},
issn = {1097-4547},
support = {2021.KB.SAG.018//Dokuz Eylül Üniversitesi/ ; 121Z900//Türkiye Bilimsel ve Teknolojik Araştırma Kurumu/ ; IG 3024//European Molecular Biology Organization/ ; },
mesh = {Animals ; Zebrafish ; *Catechin/analogs & derivatives/pharmacology/administration & dosage ; *Hydrolyzable Tannins/pharmacology/administration & dosage ; *Amyloid beta-Peptides/metabolism ; *Neurogenesis/drug effects ; *Brain/drug effects/metabolism ; *Neuroprotective Agents/pharmacology/administration & dosage ; Alzheimer Disease/metabolism/drug therapy ; Disease Models, Animal ; },
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory impairment, and behavioral alterations. The pathogenesis of AD involves the accumulation of amyloid-beta (Aβ) plaques and the hyperphosphorylated tau proteins, which disrupt neuronal function and trigger neuroinflammation. This study explores the therapeutic potential of epigallocatechin gallate (EGCG) and punicalagin (PU) in mitigating Aβ-induced toxicity using an adult zebrafish model of AD. Our results demonstrate that the EGCG + PU combination significantly reduces Aβ accumulation, protects against cellular damage, suppresses acetylcholinesterase (AChE) activity, and normalizes the expression of amyloidogenic and AD-related genes. Additionally, EGCG + PU treatment alleviates neuroinflammation by suppressing glial activation, including reductions in L-plastin and proinflammatory cytokine expression, while promoting neuronal recovery through mechanisms of neurogenesis and neuroprotection. Notably, the combination treatment restored neuronal density and improved behavioral outcomes by alleviating anxiety- and aggression-like behaviors associated with Aβ toxicity. These results underscore the synergistic neuroprotective effects of EGCG + PU, highlighting their potential as a novel therapeutic approach for mitigating the pathological, behavioral, and inflammatory aspects of AD.},
}

Animals
Zebrafish
*Catechin/analogs & derivatives/pharmacology/administration & dosage
*Hydrolyzable Tannins/pharmacology/administration & dosage
*Amyloid beta-Peptides/metabolism
*Neurogenesis/drug effects
*Brain/drug effects/metabolism
*Neuroprotective Agents/pharmacology/administration & dosage
Alzheimer Disease/metabolism/drug therapy
Disease Models, Animal

@article {pmid41673096,
year = {2026},
author = {Abo El-Magd, NF and Ramadan, NM and Eraky, SM},
title = {Liraglutide attenuates aluminum chloride-induced Alzheimer's disease in rats by modulating the oxLDL/LPA/LPAR1 pathway.},
journal = {Communications biology},
volume = {},
number = {},
pages = {},
doi = {10.1038/s42003-026-09531-z},
pmid = {41673096},
issn = {2399-3642},
abstract = {Aluminum toxicity in rodents is well documented to be used for inducing experimental models that mimic the clinical phenotypes of Alzheimer's disease (AD). Liraglutide is a well-known antidiabetic drug promising for modulating neurodegenerative conditions. Thus, investigating the ameliorative effects of Liraglutide on AD induced by aluminum chloride (AlCl3), highlighting the role of lysophosphatidic acid (LPA)/ β-secretase 1 (BACE1), is promising. Male rats are subdivided into four groups. Except for the normal group, animals are subjected to daily administration of AlCl3 (70 mg/kg, i.p.) for 45 days. Along with AlCl3, Liraglutide (0.3 mg/kg twice daily, s.c.) and Donepezil (1 mg/kg daily, i.p.) therapy are administered in AlCl3 + Lira and AlCl3 + Done groups, respectively. Liraglutide significantly ameliorates AlCl3-induced anxiety, depression-like behaviors, and deficits in memory functions. Liraglutide therapy retains the histopathological structure of the brain, with antioxidant and anti-apoptotic abilities. Moreover, Liraglutide successfully decreases hippocampal levels of oxidized low-density lipoprotein (oxLDL), LPA, lysophosphatidic acid receptor 1 (LPAR1), and β-secretase 1 (BACE1) compared with the AlCl3 group. Thus, liraglutide shows neuroprotective effects mediated by downregulation of the oxLDL/LPA/LPAR1/BACE1 pathway, which is studied for the first time to our knowledge.},
}

@article {pmid41673049,
year = {2026},
author = {Gider, V and Budak, C},
title = {A physics-informed graph neural network to approximate docking-based binding affinity for DYRK2 in Alzheimer's drug repurposing.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-35102-7},
pmid = {41673049},
issn = {2045-2322},
support = {MÜHENDİSLİK.25.024//Dicle Üniversitesi/ ; },
abstract = {Alzheimer's disease (AD) requires the discovery of new therapeutic targets, but traditional molecular docking methods for virtual screening are often computationally expensive. This study introduces PhysDual-GCN, a physics-informed graph neural network designed to approximate docking-derived binding affinity scores for DYRK2, an understudied yet biologically relevant target in Alzheimer's disease (AD). The model jointly processes ligand molecular graphs and a sequence-based graph representation of DYRK2, while explicitly incorporating Coulomb and Lennard-Jones interaction terms as analytical physical energy components. Because no experimentally measured binding affinities are available for DYRK2-drug pairs, all reference labels used for evaluation were obtained exclusively from widely used classical docking tools (AutoDock Vina, Smina, QVina, CB-DOCK). These tools exhibit an inherent uncertainty of approximately ± 0.5-1.5 kcal/mol, which constrains the interpretability of absolute deviations. PhysDual-GCN was trained solely on docking-derived scores and evaluated using a strict ligand-level separation to avoid circularity during model development. Due to the limited number of ligands (n = 4 FDA-approved AD drugs: brexpiprazole, donepezil, galantamine, rivastigmine), the results should be viewed as agreement with computational references rather than generalizable predictive performance. The model achieved low absolute errors (MAE = 0.31 kcal/mol; RMSE = 0.44 kcal/mol) relative to the reference docking scores and correctly identified stronger binders such as donepezil (- 10.8 kcal/mol) and brexpiprazole (- 10.0 kcal/mol). These findings demonstrate that integrating physical interaction terms into a GNN framework can enhance interpretability while providing a computationally efficient surrogate for classical docking workflows. Overall, PhysDual-GCN offers a biologically meaningful and explainable approximation tool for DYRK2 interaction scoring. While the present results are constrained by the small number of compounds and the absence of 3D protein features, the approach establishes a foundation for future large-scale, experimentally validated studies in AD drug repurposing.},
}

@article {pmid41673042,
year = {2026},
author = {Samardžija, B and Renner, É and Palkovits, M and Bradshaw, NJ},
title = {Levels of aggregation of proteins related to mental illness, assayed by insolubility, vary across the brains of individuals.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-35767-0},
pmid = {41673042},
issn = {2045-2322},
support = {NAP2022-I-4/2022//Magyar Tudományos Akadémia/ ; TKP 2021 EGA-25//Semmelweis Egyetem/ ; IP-2022-10-2745 & DOK-2020-01-8580//Hrvatska Zaklada za Znanost/ ; 1142747-HRV-IP//Alexander von Humboldt-Stiftung/ ; },
abstract = {An emerging area of research into major mental illnesses is to investigate the formation of insoluble aggregates of specific proteins in the brains of patients with these conditions. These studies are normally based on examining insoluble protein in post mortem brain samples, but, for practical reasons, typically consider only one region of the brain per subject. Here, we tested post mortem brain samples from multiple brain regions of various individuals, which included patients with major depressive disorder, schizophrenia and victims of suicide. Samples from patients with Alzheimer's disease and control individuals were used for comparison. Notably, 20 tissue samples were available from across the brain of one individual who had both schizophrenia and Alzheimer's disease. Consistently, while insolubility of DISC1 (Disrupted in Schizophrenia 1), CRMP1 (Collapsin Response Mediator Protein 1) and/or TRIOBP-1 (Trio and F-actin Binding Protein, isoform 1) were often present in multiple brain regions, this was not homogenous across the brain. While this study looks at a relatively small number of subjects, and caution must be taken in over-generalising, it is possible that aggregation of these proteins spreads throughout the brain, in a similar manner to the staging seen in neurodegenerative disease. Previous studies may therefore have underestimated the prevalence of protein aggregation in mental illness, due to this heterogeneity of insoluble protein across the brain.},
}

@article {pmid41672602,
year = {2026},
author = {},
title = {New treatments for Alzheimer's disease.},
journal = {BMJ (Clinical research ed.)},
volume = {392},
number = {},
pages = {s273},
doi = {10.1136/bmj.s273},
pmid = {41672602},
issn = {1756-1833},
}

@article {pmid41672403,
year = {2026},
author = {Fenton, L and Aslanyan, V and Jacobs, DM and Salmon, DP and Brewer, JB and Rissman, RA and Shadyab, AH and Harrison, TM and Evans, AC and LaCroix, AZ and Feldman, HH and Baker, LD and Pa, J},
title = {Relationships between fine memory discrimination and tau burden in two independent cohorts of older adults.},
journal = {Neuropsychologia},
volume = {},
number = {},
pages = {109393},
doi = {10.1016/j.neuropsychologia.2026.109393},
pmid = {41672403},
issn = {1873-3514},
abstract = {Cognitive assessments sensitive to the integrity of the medial temporal lobe, an area vulnerable to early tau deposition, may serve as low-cost adjunctive markers of underlying tau pathology in older adults. The Mnemonic Similarity Task (MST) is a fine memory discrimination task designed to assess hippocampal integrity. The current cross-sectional study utilized baseline data from two AD prevention trials (the Anti-Amyloid Treatment in Asymptomatic Alzheimer's (A4) study and the Exercise in Adults with Mild Memory Problems (EXERT) trial) to examine relationships between MST performance, amyloid-beta, tau, and hippocampal volume. We additionally explored relationships between performance on a traditional memory test, Logical Memory, and AD-related brain measures. Poorer fine memory discrimination was associated with higher tau as assessed by PET in A4 (N=407, 59% female, mean age=71.66, age range=65-85) and CSF (p-tau181, total tau) in EXERT (N=41, 61% female, mean age=74.10, age range=65-89). Poorer fine memory discrimination was also associated with higher amyloid PET in A4 and smaller hippocampal volume in EXERT. Poorer delayed recall on Logical Memory was associated with higher tau and amyloid burden in A4 and with lower hippocampal volume in EXERT. Poorer retention on Logical Memory was associated with higher tau in Braak I and amyloid in A4 and with CSF tau and lower hippocampal volume in EXERT. These results support the potential of fine memory discrimination as measured by the MST as an adjunctive, accessible screening measure associated with higher tau in cognitively normal, amyloid positive older adults and older adults with amnestic MCI.},
}

@article {pmid41672382,
year = {2026},
author = {Khan, S and Imam, A and Singh, S and Ahmed, A and Hassan, MI and Shahid, M and Athar, F and Islam, A},
title = {Exploring the intersection of Alzheimer's disease and comorbidities: a review of the interplay between multiple chronic conditions.},
journal = {Biochimica et biophysica acta. Molecular basis of disease},
volume = {},
number = {},
pages = {168190},
doi = {10.1016/j.bbadis.2026.168190},
pmid = {41672382},
issn = {1879-260X},
abstract = {Alzheimer's disease (AD) represents degenerative brain disorder that impairs both cognitive functions and daily living activities gradually. It is frequently linked with other disorders such as psychosis, cardiovascular disorders, diabetes, and depression, all of which may influence the disease's onset, trajectory, and treatment approaches. These comorbidities can affect the onset, progression, and management of AD. This review focuses to explore the interplay of AD and comorbidities, and to examine the interplay between multiple chronic conditions. The review found that AD and comorbidities have a complex and bidirectional relationship. Comorbidities can affect the onset, progression, and management of AD, and AD can also affect the management and outcomes of comorbidities. The review also found that comorbidities may have an impact on caregiver burden, healthcare utilization and mortality. The findings suggest that the management of AD should take into account the presence and management of comorbidities to improve the overall outcomes for patients with AD. The literature also suggests that the management of comorbidities should be integrated in the management of AD patients. Furthermore, the review highlights the critical role of timely detection and treatment of comorbidities in AD patients to delay onset and mitigate disease progression. Additionally, it is crucial to consider the influence of comorbidities when selecting treatment options and the management of side effects and adverse events in AD patients. The literature reviewed in this article suggests that a multidisciplinary approach is needed in managing AD patients with comorbidities, which includes regular screening, early detection, and management of comorbidities in addition to managing AD.},
}

@article {pmid41672338,
year = {2026},
author = {Goetzl, EJ},
title = {Cognition-Preserving Exercise Therapy for Neurodegenerative Diseases of the Elderly.},
journal = {The American journal of medicine},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.amjmed.2026.01.046},
pmid = {41672338},
issn = {1555-7162},
}

@article {pmid41672293,
year = {2026},
author = {Ge, Y and Weng, Y and Chen, Y},
title = {Elucidating the toxicological impact and mechanism of plasticizers exposure on Alzheimer's disease through network toxicology and molecular docking.},
journal = {Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association},
volume = {},
number = {},
pages = {116005},
doi = {10.1016/j.fct.2026.116005},
pmid = {41672293},
issn = {1873-6351},
abstract = {This study aimed to explore the underlying mechanisms and key targets of widely used plasticizers, including dimethyl phthalate (DMP), diethyl phthalate (DEP), and dioctyl phthalate (DOP), to the pathogenesis of Alzheimer's disease (AD). Network toxicology, molecular docking, and dynamics simulation screened candidate targets for plasticizer in increasing AD risk. Three machine learning algorithms and two microarray datasets identified key targets, whose immune relevance was assessed by CIBERSORT. An Aβ42-induced BV2 microglia model validated their role. We identified 83 plasticizer targets relevant to AD, which were enriched in KEGG pathways like apoptosis and neuroactive ligand-receptor interaction. CDK5, SLC2A1, and STAT3 were confirmed as key targets, showing consistent differential expression in two AD datasets. Their expression correlated with M1 macrophage infiltration. Molecular docking and dynamics simulations demonstrated that plasticizers stably bind these targets with high affinity. In Aβ42-induced BV2 microglia, phthalate treatment elevated inflammatory factors (TNF-α, IL-1β, IL-6) and STAT3 expression. This study demonstrated the possible mechanistic associations between plasticizers exposure and AD, and STAT3 might be key target of plasticizers.},
}

@article {pmid41672268,
year = {2026},
author = {de Melo Silva, JG and de Medeiros Barros, W and Lopes, NMCP and Bellozi, PMQ},
title = {Alzheimer's disease: Current therapeutic strategies and emerging perspectives for multifactorial intervention.},
journal = {Progress in neuro-psychopharmacology & biological psychiatry},
volume = {},
number = {},
pages = {111640},
doi = {10.1016/j.pnpbp.2026.111640},
pmid = {41672268},
issn = {1878-4216},
abstract = {Alzheimer's Disease (AD) is a progressive, multifactorial neurodegenerative condition and the most common form of dementia, affecting millions globally. Its incidence increases with age and is characterized by cognitive decline, functional impairments, and behavioral disturbances. Although its etiology remains unclear, AD is believed to result from a complex interaction between genetic, environmental, and lifestyle factors. Several hypotheses have been proposed to explain its pathogenesis, including the amyloid cascade, tau neurofibrillary tangle formation, cholinergic and glutamatergic dysfunctions, and, more recently, lipid invasion. Current treatment strategies involve both pharmacological and non-pharmacological interventions. In Brazil, acetylcholinesterase inhibitors and memantine are widely used. Recently, efforts have focused on developing new therapies, such as monoclonal antibodies, with three representatives already approved by the FDA, in addition to innovative approaches such as the use of technology and virtual reality for cognitive therapies. However, there is still a need for research that enables early diagnosis, interventions with fewer adverse effects, and the development of therapies targeting multiple mechanisms. Therefore, the pursuit of more effective and personalized treatments is essential to mitigate the societal impacts of AD.},
}

@article {pmid41672158,
year = {2026},
author = {Liu, Z and Wang, J and Ge, Y and Wang, Y and Ling, H and Liu, Y and Zhang, J and You, Z and Han, Y},
title = {PPARγ in microglia helps protect adolescent male mice from harmful effects of stress during early development.},
journal = {Brain, behavior, and immunity},
volume = {},
number = {},
pages = {106483},
doi = {10.1016/j.bbi.2026.106483},
pmid = {41672158},
issn = {1090-2139},
abstract = {Deficiency in the expression or activity of the nuclear hormone receptor peroxisome proliferator-activated receptor γ (PPARγ) has been observed in autism spectrum disorder, bipolar disorder and Alzheimer's disease. Here we showed that separating mouse pups from their mothers for three hours daily during the first two weeks of life downregulated PPARγ, leading to pro-inflammatory polarization and activation of microglia in the hippocampus, which results in more severe responses to subsequent chronic restraint stress in adolescent animals. These effects of maternal separation were reversed by activating PPARγ with pioglitazone at 30 mg/kg/day for one week, which also stimulated hippocampal neurogenesis. Knocking out PPARγ specifically in microglia reduced neural activity and dendritic spine density in the cortex and hippocampus and led to depressive-like behaviors in mice. These results suggest that PPARγ expression enables microglia to "remember" previous exposure to stress and thereby influence responses to future stress. The findings may help guide interventions against stress and related psychological disorders.},
}

@article {pmid41672153,
year = {2026},
author = {Zhu, L and Mao, Q and Luo, Z and Chen, B and Zhang, Y and Lu, X and Liu, P and Ji, J and Wang, X and Wang, K and Pan, X and Cao, Y and Liu, N and Zheng, J and Wang, F and Yang, K and Yang, F and Yu, Z and Hu, J and Luo, J and Zuo, L and Wang, Z and Luo, X and Guo, X},
title = {Phenome-wide association study of P2RX7 identifies schizophrenia and mood disorders as primary associated phenotypes.},
journal = {Journal of affective disorders},
volume = {},
number = {},
pages = {121327},
doi = {10.1016/j.jad.2026.121327},
pmid = {41672153},
issn = {1573-2517},
abstract = {OBJECTIVES: P2RX7 has been implicated in bipolar disorder, major depressive disorder, schizophrenia, anxiety disorders, Alzheimer's disease, and Parkinson's disease. However, the specificity and comparability of these associations remain unclear. This study aimed to systematically evaluate multiple neuropsychiatric disorders to identify those most robustly associated with P2RX7.

METHODS: We analyzed 1861 imputed SNPs spanning the P2RX7 gene in 1,087,925 individuals from 72 independent cohorts across 18 neuropsychiatric disorders. SNP-disease associations were assessed within each cohort, followed by meta-analysis and false discovery rate (FDR) correction to identify significant disease-risk variants. P2RX7 mRNA and protein expression across tissues or cells was characterized. Functional analyses evaluated the regulatory effects of disease-associated SNPs on P2RX7 mRNA expression, subcortical gray matter volumes (GMVs), cortical surface area (SA), and cortical thickness (TH).

RESULTS: Bipolar disorder showed the strongest association with P2RX7 variants in European Americans (EAs) (4.0 × 10[-8] ≤ p ≤ 0.004; 3.8 × 10[-5] ≤ q ≤ 0.05), followed by schizophrenia in EAs (8.9 × 10[-6] ≤ p ≤ 2.6 × 10[-4]; 9.4 × 10[-3] ≤ q ≤ 0.043) and Chinese populations (2.1 × 10[-5] ≤ p ≤ 1.7 × 10[-3]; 6.8 × 10[-3] ≤ q ≤ 0.049), and major depression in both EAs (p = 4.1 × 10[-5]; q = 0.030) and Chinese (4.3 × 10[-5] ≤ p ≤ 0.009; 6.1 × 10[-3] ≤ q ≤ 0.046). The significance of most associations and their relative ranking across disorders was maintained in the trans-ancestry meta-analysis. Expression analysis revealed that P2RX7 mRNA and protein expression were abundant in the brain, glial cells and macrophages. Approximately half of the disease-associated SNPs significantly influenced P2RX7 mRNA expression in nine brain regions (1.0 × 10[-7] ≤ p ≤ 0.047) and altered GMV, SA, and TH of seven brain regions (1.9 × 10[-4] ≤ p ≤ 3.4 × 10[-3]).

CONCLUSION: P2RX7 is most consistently and specifically associated with bipolar disorder, schizophrenia, and major depression, supported by both statistical and biological evidence.},
}

@article {pmid41672134,
year = {2026},
author = {Maneu, V and García, AG},
title = {P2X7 receptors as targets for neuroprotection.},
journal = {Neuropharmacology},
volume = {},
number = {},
pages = {110877},
doi = {10.1016/j.neuropharm.2026.110877},
pmid = {41672134},
issn = {1873-7064},
abstract = {In this review we explore the potential of P2X7 receptor blockers to elicit neuroprotection. This conjecture is based on a reasonably well-established role of this receptor in activating glial cells to maintain a chronic low-level neuroinflammatory state in the brain of patients suffering some neurodegenerative diseases (NDDs). In this context we briefly discuss evidence supporting the role of P2X7 receptors (P2X7) in the pathogenesis of Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, multiple sclerosis, and retinal degeneration. From a pathogenic point of view these diseases have specific features but all share a low level neuroinflammatory state with microglia activation and enhanced P2X7 expression. Next, we comment on available P2X7 blockers with central nervous system (CNS) target engagement. Then, we deal with the proof-of-concept concerning the potential of some blockers to mitigate the neuroinflammatory state in preclinical models of the target diseases above mentioned. We follow with a discussion of the scarce number of clinical trials done with some P2X7 blockers in inflammatory diseases. Finally, we discuss the current discrepancy between promising preclinical data and the limited number of clinical trials exploring P2X7 antagonists in NDDs. We provide some clues that may boost clinical trials with single P2X7 blockers but particularly, with their association with other medicines currently being used or that are intended to be prescribed in the treatment of NDDs.},
}

@article {pmid41672112,
year = {2026},
author = {Liu, C and Li, X and Pu, W and Jing, J and Cui, W and Liu, G and Cai, L},
title = {Multi-Time points RNA-seq Screening Identifies Key Transcription Factors and Splicing Factors Responsive to Intermittent Hypoxia in the Mouse Hippocampus.},
journal = {Free radical biology & medicine},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.freeradbiomed.2026.02.005},
pmid = {41672112},
issn = {1873-4596},
abstract = {Intermittent hypoxia (IH) is a hallmark pathological feature of obstructive sleep apnea and a critical risk factor for neurodegenerative diseases such as Alzheimer's disease. Transcription factors (TFs) and splicing factors (SFs) serve as pivotal regulators orchestrating cellular adaptations to hypoxia. This study aimed to elucidate the dynamic changes and identify candidate key TFs and SFs in the mouse hippocampus under IH. By establishing an IH mouse model (7% O2, 1/3/5/7 weeks) and integrating multi-time points RNA-seq with bioinformatic analysis and experimental validation, we systematically identified putative core TFs and SFs involved in hippocampal hypoxia response and inferred their potential functions. Our study revealed that the TFs Lef1 and Foxj1, along with the SF Rbm47, emerge as candidate key regulators. Lef1 may modulate apoptosis-related genes such as Il31ra, while Foxj1 could be linked to ciliary function and neural development by regulating genes like Rsph1. The SF Rbm47 potentially contributes to hippocampal hypoxic adaptation by modulating alternative splicing of genes such as Apc and Hnrnpa2b1. The Lef1 gene itself undergoes alterations in exon retention rates during intermittent hypoxia. These findings provide critical data to decipher hippocampal IH adaptation and offer theoretical insights into the mechanisms of AD and related neurodegenerative disorders.},
}

@article {pmid41672073,
year = {2026},
author = {Berdugo-Vega, G and Sierra, C and Astori, S and Calati, V and Orsat, J and Scoglio, MJ and Sandi, C and Gräff, J},
title = {Cognitive rejuvenation through partial reprogramming of engram cells.},
journal = {Neuron},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neuron.2025.11.028},
pmid = {41672073},
issn = {1097-4199},
abstract = {Counteracting cognitive decline is a declared goal of regenerative medicine. Recently, partial cellular reprogramming has emerged as a promising strategy to promote tissue regeneration and restore cellular function, but whether this approach bears fruit when targeted to cell populations underlying cognitive processes remains unknown. Here, we report that partial reprogramming of engram neurons-bona fide memory trace cells-by OSK-mediated gene therapy reversed the expression of senescence- and disease-related cellular hallmarks in aged mice and models of Alzheimer's disease (AD), re-established aberrant epigenetic-transcriptional patterns pertaining to synaptic plasticity, and counteracted AD-typical neuronal hyperexcitability. Importantly, irrespective of the brain area targeted or the behavioral paradigm employed, engram reprogramming also recovered learning and memory capacities to levels of healthy young animals, suggesting cognitive rejuvenation. These results posit that partial reprogramming of specific cell populations in the brain can be exploited for cognitive restoration in aging and disease.},
}

@article {pmid41672038,
year = {2026},
author = {Masuda, T},
title = {Microglia makeover: On-demand control panel revamp.},
journal = {Immunity},
volume = {59},
number = {2},
pages = {229-231},
doi = {10.1016/j.immuni.2026.01.007},
pmid = {41672038},
issn = {1097-4180},
mesh = {*Microglia/physiology/immunology/metabolism ; Humans ; Animals ; Epigenesis, Genetic ; *Alzheimer Disease/genetics/immunology ; Enhancer Elements, Genetic ; },
abstract = {Microglia display remarkable plasticity, with their cellular states evolving in response to developmental stage, regional context, and environmental or pathological stimuli. In this issue of Immunity, Hamagami et al. demonstrate that adaptive reconfiguration of regulatory networks, particularly the dynamics of enhancers, underlies these state transitions. Conserved enhancers link developmental and Alzheimer's-related microglial states, suggesting shared epigenetic frameworks that influence neurodegenerative susceptibility.},
}

*Microglia/physiology/immunology/metabolism
Humans
Animals
Epigenesis, Genetic
*Alzheimer Disease/genetics/immunology
Enhancer Elements, Genetic

@article {pmid41671870,
year = {2026},
author = {Morihara, R and Nomura, E and Osakada, Y and Yunoki, T and Takemoto, M and Yamashita, T and Ishiura, H},
title = {Real-world evaluation of Armstrong's criteria in corticobasal degeneration: Phenotypic overlap and diagnostic challenges.},
journal = {Parkinsonism & related disorders},
volume = {145},
number = {},
pages = {108229},
doi = {10.1016/j.parkreldis.2026.108229},
pmid = {41671870},
issn = {1873-5126},
abstract = {BACKGROUND: Corticobasal degeneration (CBD) is a four-repeat tauopathy with heterogeneous clinical manifestations. Armstrong's criteria involve a two-step diagnostic approach: first, classifying patients into five clinical phenotypes-probable/possible corticobasal syndrome (CBS), frontal behavioral-spatial syndrome (FBS), non-fluent/agrammatic variant primary progressive aphasia (naPPA), and progressive supranuclear palsy syndrome (PSPS); second, determining whether they meet the clinical research criteria for probable CBD (cr-CBD) or the clinical criteria for possible CBD (p-CBD), which are distinct from the initial CBS classifications.

OBJECTIVE: To investigate how real-world patients with suspected CBD fulfill Armstrong's clinical phenotypes and diagnostic criteria, and to compare clinical and imaging features between the Alzheimer's disease (AD) group and the non-AD group defined by CSF amyloid biomarkers.

METHODS: We retrospectively reviewed 137 patients undergoing differential diagnosis for CBS, frontotemporal dementia, primary progressive aphasia, or PSPS. Of these, 78 met the criteria for cr-CBD (n = 36) or p-CBD (n = 42). CSF was examined in 32 patients, and based on the CSF Aβ42/40 ratio, patients were classified into an AD-group (AD-CBS; n = 6) and a non-AD group (n = 26).

RESULTS: Among patients classified as cr-CBD or p-CBD, 79% fulfilled two or more clinical phenotypes, with FBS and PSPS most commonly. Compared with the AD group, the non-AD group showed more parkinsonian features and frontal hypoperfusion on [[123]I]-IMP SPECT.

CONCLUSION: Armstrong's criteria captured a spectrum of overlapping clinical features. While helpful in clinical phenotyping, further validation with biomarkers is essential to distinguish CBD from AD and related disorders. Prospective studies with pathological confirmation are warranted.},
}

@article {pmid41671778,
year = {2026},
author = {Jayaswal, RP and Chaubey, KK and Sharma, S and Singh, M and Kholiya, K},
title = {Histochemical perspectives on VDAC1-associated autophagy signaling in Alzheimer's disease brain.},
journal = {Acta histochemica},
volume = {128},
number = {2},
pages = {152328},
doi = {10.1016/j.acthis.2026.152328},
pmid = {41671778},
issn = {1618-0372},
}

@article {pmid41671691,
year = {2026},
author = {da Silva, AMP and de Deus, O and Januário Campos Cardoso, L and Virgilio Ribeiro, F and Froelich Meldola, P and Rodrigues Menezes, I and Lee Han, M and Quiroga, DG and James Almeida, K and Haddad Santos, D and Perry, G and Høilund-Carlsen, PF and de Souza Franco, E and de Sousa Maia, MB},
title = {Efficacy, safety, and ARIA risk of anti-β-amyloid antibodies in early Alzheimer's disease: a systematic review, meta-analysis, and meta-regression.},
journal = {Expert opinion on biological therapy},
volume = {},
number = {},
pages = {},
doi = {10.1080/14712598.2026.2631536},
pmid = {41671691},
issn = {1744-7682},
abstract = {BACKGROUND: Alzheimer's disease (AD) is the most prevalent cause of dementia and has been closely linked to β-amyloid accumulation. However, the efficacy and safety of anti-β-amyloid monoclonal antibodies remain debated.

METHODS: We systematically searched PubMed, Embase, and Cochrane databases for RCTs comparing anti-β-amyloid monoclonal antibodies with placebo in early-stage AD. Eligible trials enrolled participants with biomarker-supported AD and reported global, cognitive, or safety outcomes, including the CDR-SB, ADAS-Cog 13/14, ARIA, and brain volumetric measures.

RESULTS: Six RCTs including 7837 participants were analyzed. Mean age ranged from 69.8 to 75.4 years, and 57.4% were APOE ε4 carriers. Anti-β-amyloid therapy was associated with small differences in global and cognitive outcomes, best described as a modest slowing of decline on the CDR-SB and ADAS-Cog scales. Treatment was associated with increased risks of ARIA-E (RR, 9.40; 95% CI, 6.98-12.66) and ARIA-H (RR, 2.40; 95% CI, 2.08-2.78), as well as greater ventricular enlargement and hippocampal atrophy.

CONCLUSION: In early AD, anti-β-amyloid monoclonal antibodies are associated with modest slowing of decline accompanied by increased ARIA risk and unfavorable structural brain changes, limiting clinical applicability.

PROTOCOL REGISTRATION: http://www.crd.york.ac.uk/prospero identifier is CRD420251071393.},
}

@article {pmid41671614,
year = {2026},
author = {Li, Z and Tan, B and Dong, K and Yu, X and Zhang, SW and Luo, L and Yao, W and Qin, Z and Wu, F},
title = {Cobrotoxin mitigates neuroinflammation and cognitive impairment by suppressing CD8[+] T cell-microglia interactions in male 5 × FAD mice.},
journal = {Biochemical pharmacology},
volume = {247},
number = {},
pages = {117779},
doi = {10.1016/j.bcp.2026.117779},
pmid = {41671614},
issn = {1873-2968},
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline accompanied by chronic neuroinflammation. Emerging evidence implicates T-cell infiltration and microglial activation as key immune events that accelerate AD pathology, yet therapeutic approaches targeting this neuroimmune interface remain scarce. Cobrotoxin (CTX), a short-chain neurotoxin derived from Naja atra venom, exhibits potent anti-inflammatory and immunomodulatory properties and is clinically approved in China for the treatment of chronic pain syndromes. Here, we investigated whether CTX could alleviate neuroinflammation and cognitive deficits in 5 × FAD mice, a transgenic model of AD. Intranasal CTX administration for nine weeks enhanced spatial learning and memory in the Morris water maze without altering amyloid-β burden. Flow cytometry and immunofluorescence revealed that CTX markedly reduced brain-infiltrating CD8[+] T cells and downregulated chemokines implicated in T cell-microglia communication, including Cxcl9, Cxcl10, Cxcl16, and Ccl5. Consistent with this, CTX attenuated microglial activation and pro-inflammatory cytokine release while preserving plaque-associated microglia (disease-associated microglia, DAM). Morphological and electrophysiological analyses demonstrated that CTX restored dendritic complexity, spine density, and hippocampal long-term potentiation (LTP), indicating improved synaptic integrity. Collectively, these findings identify CTX as a potent modulator of neuroimmune signaling that mitigates neuroinflammation and synaptic dysfunction in AD, suggesting its potential for repurposing as an immunomodulatory therapy for neurodegenerative diseases.},
}

@article {pmid41671519,
year = {2026},
author = {Zammit, AR and Yu, L and Poole, VN and Kapasi, A and Wilson, RS and Bennett, DA},
title = {Associations of Lifetime Cognitive Enrichment With Incident Alzheimer Disease Dementia, Cognitive Aging, and Cognitive Resilience.},
journal = {Neurology},
volume = {106},
number = {5},
pages = {e214677},
doi = {10.1212/WNL.0000000000214677},
pmid = {41671519},
issn = {1526-632X},
mesh = {Humans ; Female ; *Alzheimer Disease/epidemiology/pathology/psychology ; Male ; Aged ; Aged, 80 and over ; Longitudinal Studies ; *Cognitive Dysfunction/epidemiology/pathology/psychology ; *Cognitive Aging/psychology ; *Resilience, Psychological ; *Cognition/physiology ; },
abstract = {BACKGROUND AND OBJECTIVES: The effects of lifetime cognitive enrichment on later-life cognitive outcomes are not comprehensively investigated. The aim of this study was to test the association of lifetime cognitive enrichment with Alzheimer disease (AD) dementia and cognitive decline and in an autopsied deceased subset to explore the association between lifetime enrichment and AD and related dementia (ADRD) pathologic indices and cognitive resilience that is, decline after adjusting for common ADRD pathologies.

METHODS: This was a longitudinal clinicopathologic study involving older individuals from Northeastern Illinois who participated in the Rush Memory and Aging Project, were free of dementia at baseline, completed surveys reflecting lifetime enrichment, and had annual clinical evaluations. We constructed a composite measure reflecting lifetime cognitive enrichment and tested its association with incident AD dementia in proportional hazards models, mean age of AD dementia onset in an accelerated failure time model, and cognitive decline using linear mixed-effects models. In a deceased subset, we tested the association of lifetime cognitive enrichment with 9 ADRD pathologies and cognitive resilience.

RESULTS: Participants (n = 1,939, 75% female, mean baseline age = 79.6) completed an average of 7.6 years of follow-up, during which 551 participants developed AD dementia. One unit higher in lifetime enrichment was associated with 38% lower hazards of developing AD dementia (hazard ratio 0.62, 95% CI 0.52-0.73, p < 0.001). High lifetime enrichment (90th percentile) compared with low (10th percentile) was associated with a mean of 5 years delayed onset of AD dementia. Lifetime enrichment was positively associated with cognitive function at baseline (estimate = 0.31, SE = 0.02, p < 0.001) and a slower rate of cognitive decline (estimate = 0.02, SE = 0.01, p = 0.002). In the deceased subset (n = 948), lifetime cognitive enrichment did not show meaningful associations with neuropathologic indices, but remained associated with higher cognitive function proximate to death (estimate = 0.32, SE = 0.06, p < 0.001) and a slower rate of cognitive decline after adjusting for pathology (estimate = 0.014, SE = 0.01, p = 0.02).

DISCUSSION: Lifetime exposure to cognitive enrichment was related to lower risk of AD dementia and a slower rate of cognitive decline, including after adjustment for common ADRD pathologies, indicating higher resilience provided by lifetime enrichment. Our results suggest that cognitive health in later life is in part the product of lifetime exposure to cognitive enrichment.},
}

Humans
Female
*Alzheimer Disease/epidemiology/pathology/psychology
Male
Aged
Aged, 80 and over
Longitudinal Studies
*Cognitive Dysfunction/epidemiology/pathology/psychology
*Cognitive Aging/psychology
*Resilience, Psychological
*Cognition/physiology

@article {pmid41671378,
year = {2026},
author = {Huang, D and Ovcharenko, I},
title = {Silencer variants are key drivers of gene up-regulation in Alzheimer's disease.},
journal = {Science advances},
volume = {12},
number = {7},
pages = {eadz3323},
doi = {10.1126/sciadv.adz3323},
pmid = {41671378},
issn = {2375-2548},
mesh = {*Alzheimer Disease/genetics/metabolism/pathology ; Humans ; *Up-Regulation ; Polymorphism, Single Nucleotide ; Genetic Predisposition to Disease ; Enhancer Elements, Genetic ; *Genetic Variation ; },
abstract = {The genetic mechanisms of ~90% of Alzheimer's disease (AD)-associated variants residing in noncoding DNA remain poorly understood. To address this, we developed a deep learning framework that integrates bulk histone modification data with single-cell open chromatin profiles to evaluate the regulatory potential of noncoding variants. This model identified 1457 silencer and 3084 enhancer AD-associated variants in dorsolateral prefrontal cortex, classifying gene loci as silencer-only (SL), enhancer-only (EN), or dual-function (ENSL). EN loci predominantly regulate housekeeping metabolic processes, SL loci (including MS4A6A and HLA-D) are linked to immune responses (with ~70% substantially up-regulated in AD microglia), while ENSL loci are implicated in neurofibrillary tangle assembly. Our model achieves robust power in assessing the impact of regulatory variants, with ~70% directional concordance with experimental results. It identified rs636317 as a putative causal silencer variant, distinguishing it from a neutral variant located 11 base pairs away. This study advances understanding of the AD-associated regulatory landscape and provides a framework for ascertaining noncoding variants in AD pathogenesis.},
}

*Alzheimer Disease/genetics/metabolism/pathology
Humans
*Up-Regulation
Polymorphism, Single Nucleotide
Genetic Predisposition to Disease
Enhancer Elements, Genetic
*Genetic Variation

@article {pmid41671338,
year = {2026},
author = {Rao, NR and Santiago-Marrero, I and DeGulis, O and Nomura, T and Goyal, K and Lee, S and Hark, TJ and Dynes, JC and Dexter, EX and Dulewicz, M and Ge, J and Upadhyay, A and Fornasiero, EF and Vassar, R and Hanrieder, J and Contractor, A and Savas, JN},
title = {Levetiracetam prevents Aβ production through SV2a-dependent modulation of APP processing in Alzheimer's disease models.},
journal = {Science translational medicine},
volume = {18},
number = {836},
pages = {eadp3984},
doi = {10.1126/scitranslmed.adp3984},
pmid = {41671338},
issn = {1946-6242},
mesh = {*Levetiracetam/pharmacology ; Animals ; *Alzheimer Disease/metabolism/drug therapy/pathology ; Disease Models, Animal ; *Amyloid beta-Protein Precursor/metabolism ; *Amyloid beta-Peptides/metabolism/biosynthesis ; Mice, Transgenic ; *Membrane Glycoproteins/metabolism ; *Nerve Tissue Proteins/metabolism ; Mice ; Synaptic Vesicles/metabolism/drug effects ; Humans ; Synapses/metabolism/drug effects ; Peptide Fragments/metabolism ; },
abstract = {Amyloid-β (Aβ) peptides are a defining feature of Alzheimer's disease (AD). These peptides are produced by the proteolytic processing of the amyloid precursor protein (APP), which can occur through the synaptic vesicle (SV) cycle. However, how amyloidogenic APP processing alters SV composition and presynaptic function is poorly understood. Using App knock-in mouse models of amyloid pathology, we found that proteins with impaired degradation accumulate at presynaptic sites together with Aβ42 in the SV lumen. Levetiracetam (Lev) is a US Food and Drug Administration-approved antiepileptic that targets SVs and has shown therapeutic potential to reduce AD phenotypes through an undefined mechanism. We found that Lev lowers Aβ42 levels by reducing amyloidogenic APP processing in an SV2a-dependent manner. Lev modified SV cycling and increased APP cell surface expression, which promoted its preferential processing through the nonamyloidogenic pathway. Stable isotope labeling combined with mass spectrometry confirmed that Lev prevents Aβ42 production in vivo. In transgenic mice with aggressive amyloid pathology, electrophysiology and immunofluorescence confirmed that Lev restores SV cycling abnormalities and reduces synapse loss. Last, early Aβ pathology in brains from donors with Down syndrome was characterized by elevated presynaptic proteins. Together, these findings highlight the potential to prevent Aβ pathology before irreversible damage occurs.},
}

*Levetiracetam/pharmacology
Animals
*Alzheimer Disease/metabolism/drug therapy/pathology
Disease Models, Animal
*Amyloid beta-Protein Precursor/metabolism
*Amyloid beta-Peptides/metabolism/biosynthesis
Mice, Transgenic
*Membrane Glycoproteins/metabolism
*Nerve Tissue Proteins/metabolism
Mice
Synaptic Vesicles/metabolism/drug effects
Humans
Synapses/metabolism/drug effects
Peptide Fragments/metabolism

@article {pmid41670993,
year = {2026},
author = {Gray, SL and Yu, O and Gatto, NM and Marcum, ZA and Latimer, CS and Postupna, N and Su, YR and Barthold, D and van Dalen, JW and Richard, E and Keene, CD and Shaw, PA and McEvoy, LK and Larson, EB and Crane, PK},
title = {Angiotensin II-Stimulating Antihypertensive Medications and Dementia-Related Neuropathology.},
journal = {JAMA network open},
volume = {9},
number = {2},
pages = {e2559113},
doi = {10.1001/jamanetworkopen.2025.59113},
pmid = {41670993},
issn = {2574-3805},
mesh = {Humans ; Female ; Male ; *Antihypertensive Agents/therapeutic use/pharmacology ; Aged ; *Dementia/pathology/epidemiology ; *Hypertension/drug therapy ; Cohort Studies ; Aged, 80 and over ; Middle Aged ; Angiotensin Receptor Antagonists/therapeutic use ; *Angiotensin II ; },
abstract = {IMPORTANCE: Antihypertensive medications that stimulate angiotensin II type 2 or 4 receptors (angiotensin II-stimulating medications) may be associated with lower risk of dementia.

OBJECTIVE: To examine associations between cumulative exposure to angiotensin II-stimulating vs angiotensin II-inhibiting antihypertensive medications and neuropathology, accounting for blood pressure.

This community-based autopsy cohort study from the Adult Changes in Thought cohort was conducted at Kaiser Permanente Washington between February 24, 1994, and November 25, 2022, among 756 participants who had blood pressure measurements and at least 1 person-year (PY) of angiotensin II-stimulating or -inhibiting antihypertensive medication exposure prior to death. Statistical analysis was performed between September 2024 and August 2025.

EXPOSURE: Angiotensin II-stimulating antihypertensive medications (angiotensin II receptor blockers, dihydropyridine calcium channel blockers, thiazides) and angiotensin II-inhibiting antihypertensive medications (angiotensin-converting enzyme inhibitors, β-blockers, nondihydropyridine calcium channel blockers) were ascertained from paper-based medical records (before 1977) and electronic prescription fill data (after 1977). The primary exposure was cumulative angiotensin II PYs, and the secondary exposure was long-term use (≥15 years).

MAIN OUTCOMES AND MEASURES: Neuropathology outcomes were classified as Alzheimer disease related, vascular brain injury, or other. Exploratory outcomes included quantitative measures of Aβ42 and phosphorylated tau. Data were analyzed using multivariable modified Poisson, proportional odds, and linear regression models and accounted for potential selection bias.

RESULTS: The sample included 756 participants (mean [SD] age at death, 89.2 [6.4] years; 440 women [58.2%]; mean [SD] follow-up, 22.2 [13.5] years). Compared with exposure to 5 additional PYs of angiotensin II-inhibiting antihypertensive medications, exposure to 5 additional PYs of angiotensin II-stimulating antihypertensive medications was associated with a 6% lower risk for arteriolosclerosis (relative risk [RR], 0.94; 95% CI, 0.89-0.99), with long-term use associated with a 24% lower risk (RR, 0.76; 95% CI, 0.63-0.91). For exploratory outcomes, PYs of angiotensin II-stimulating antihypertensive medications were associated with less quantitative phosphorylated tau burden in several brain regions (temporal lobe [adjusted ratio of geometric means, 0.79; 95% CI, 0.62-1.00], hippocampus [adjusted ratio of geometric means, 0.83; 95% CI, 0.71-0.97], cornu ammonis subfield 1 [adjusted ratio of geometric means, 0.86; 95% CI, 0.74-0.99], and transentorhinal cortex [adjusted ratio of geometric means, 0.83; 95% CI, 0.70-0.98]) but not with Aβ42 quantitative measures.

CONCLUSIONS AND RELEVANCE: In this community-based autopsy cohort study, angiotensin II-stimulating antihypertensive medications were associated with lower risk of neuropathological burden, supporting findings from epidemiologic dementia studies. Additional mechanistic research examining the effects of individual antihypertensive classes on Alzheimer disease-related biomarkers is warranted.},
}

Humans
Female
Male
*Antihypertensive Agents/therapeutic use/pharmacology
Aged
*Dementia/pathology/epidemiology
*Hypertension/drug therapy
Cohort Studies
Aged, 80 and over
Middle Aged
Angiotensin Receptor Antagonists/therapeutic use
*Angiotensin II

@article {pmid41670794,
year = {2026},
author = {Chen, X and Huang, Y and Zhao, C and Huang, M},
title = {Association between leukocyte telomere length and neurodegenerative diseases: a prospective cohort in the UK Biobank.},
journal = {Journal of neurology},
volume = {273},
number = {2},
pages = {137},
pmid = {41670794},
issn = {1432-1459},
support = {ZDXK202252//Jiangsu Provincial Medical Key Discipline/ ; K2023014//Jiangsu Provincial Health Commission Key Medical projects/ ; GSWS2022068//Suzhou Gusu Health Talent Plan Talent Research Project/ ; },
mesh = {Humans ; Male ; Female ; *Neurodegenerative Diseases/genetics/epidemiology ; United Kingdom/epidemiology ; *Leukocytes/metabolism ; Aged ; Biological Specimen Banks ; Middle Aged ; Prospective Studies ; *Telomere ; Cohort Studies ; Aged, 80 and over ; Machine Learning ; UK Biobank ; },
abstract = {BACKGROUND: This study aims to investigate the association between leukocyte telomere length (LTL) and the risk of incident NDDs using a large-scale cohort from the UK Biobank.

METHODS: Data from 459,902 subjects were analyzed using Cox proportional hazards models and machine learning (ML) algorithms to assess LTL's association with NDD risk.

RESULTS: Shorter LTL was associated with an increased risk of NDDs, including Alzheimer's disease (HR: 0.52, 95% CI 0.40-0.67, P < 0.001), dementia in AD (HR: 0.53, 95% CI 0.39-0.73, P < 0.001), unspecified dementia (HR: 0.74, 95% CI 0.58-0.95, P < 0.05), degenerative diseases of the nervous system (including other specified degenerative diseases such as circumscribed brain atrophy and senile degeneration of the brain) (HR: 0.62, 95% CI 0.45-0.84, P < 0.01), extrapyramidal and movement disorders (including other specified extrapyramidal and movement disorders such as a range of tremors, chorea, tics, and other abnormal involuntary movements) (HR: 0.63, 95% CI 0.48-0.82, P < 0.01), and mental and behavioral disorders due to use of alcohol (HR: 0.46, 95% CI 0.38-0.55, P < 0.001). Conversely, longer LTL was associated with a 3.71-fold increased risk of multiple sclerosis (MS) (HR: 3.71, 95% CI 1.91-7.18, P < 0.001). ML models confirmed the predictive value of LTL for NDDs.

CONCLUSION: Shorter LTL increased the risk of several NDDs, while longer LTL paradoxically predisposed individuals to MS, especially in younger populations. ML models demonstrated strong potential for predicting NDD risks, enhancing our understanding of the role of telomeres in neurodegeneration.},
}

Humans
Male
Female
*Neurodegenerative Diseases/genetics/epidemiology
United Kingdom/epidemiology
*Leukocytes/metabolism
Aged
Biological Specimen Banks
Middle Aged
Prospective Studies
*Telomere
Cohort Studies
Aged, 80 and over
Machine Learning
UK Biobank

@article {pmid41670689,
year = {2026},
author = {Abedi, A and Foroutan, T and Dargahi, L},
title = {Intranasal CM-hMSCs modulate brain gene expression linked to glucose metabolism and inflammation in male and female rats exposed to maternal and post-weaning high-fat diets.},
journal = {Naunyn-Schmiedeberg's archives of pharmacology},
volume = {},
number = {},
pages = {},
pmid = {41670689},
issn = {1432-1912},
support = {4001774//Iran National Science Foundation (INSF)/ ; 26822//Research Affairs of Shahid Beheshti University of Medical Sciences/ ; },
abstract = {Peripheral metabolic disorders, which drive brain insulin resistance, increase the risk of cognitive impairment, a key contributor to Alzheimer's disease. Conditioned media derived from human mesenchymal stem cells (CM-hMSCs) have shown potential for modulating neurological pathways. Male and female offspring exposed to maternal and post-weaning high-fat diet (HFD) were treated with CM-hMSCs. Spatial memory and anxiety-like behaviors were assessed along with hippocampal markers of glucose metabolism, inflammation, and Alzheimer's disease-related pathways. In male offspring, CM-hMSCs partially improved molecular pathways involved in brain glucose metabolism, as indicated by increased hippocampal mRNA expression of Glut1, Glut4, and IDE, and elevated BDNF levels. CM-hMSC treatment also modulated the inflammatory profile, with increased IL-10 and reduced IL-1β in the hippocampus. However, CM-hMSCs did not produce significant improvements in behavioral outcomes. CM-hMSCs exert early, region-specific molecular effects on hippocampal glucose metabolism and inflammatory responses in HFD-exposed male offspring.},
}

@article {pmid41670187,
year = {2026},
author = {Bourgeat, P and Fripp, J and Lebrat, L and Xia, Y and Feizpour, A and Cox, T and Zisis, G and Gillman, A and Goyal, MS and Tosun, D and Benzinger, TL and LaMontagne, P and Breakspear, M and Lupton, MK and Short, C and Adam, R and Robertson, JS and Sperling, R and O'Bryant, SE and Johnson, SC and Jr, CRJ and Schwarz, CG and Barkhof, F and Farrar, G and Bollack, A and Collij, LE and Landau, S and Koeppe, R and , and , and , and , and , and , and , and , and , and , and , and Morris, JC and Weiner, MW and Villemagne, VL and Masters, CL and Rowe, CC and Dore, V},
title = {AI-enhanced Centiloid quantification of amyloid PET images.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {2},
pages = {e71162},
doi = {10.1002/alz.71162},
pmid = {41670187},
issn = {1552-5279},
support = {GA16788//National Health and Medical Research Council/ ; R01-AG058676-01A1/NH/NIH HHS/United States ; },
mesh = {Humans ; *Positron-Emission Tomography/methods ; *Alzheimer Disease/diagnostic imaging/metabolism ; *Amyloid beta-Peptides/metabolism ; Male ; *Deep Learning ; Female ; Aged ; *Brain/diagnostic imaging/metabolism ; *Neuroimaging/methods ; Australia ; },
abstract = {INTRODUCTION: The Centiloid scale is the standard for amyloid (Aβ) PET quantification in research and clinical settings. However, variability between tracers and scanners remains a challenge.

METHODS: This study introduces DeepSUVR, a deep learning method to correct Centiloid quantification, by penalizing implausible longitudinal trajectories during training. The model was trained using data from 2,129 participants (7,149 Aβ positron emission tomography [PET] scans) in the Australian Imaging, Biomarkers and Lifestyle Study of ageing (AIBL)/Alzheimer's Disease Neuroimaging Initiative (ADNI) and validated using 15,807 Aβ PET scans from 10,543 participants across 10 external datasets.

RESULTS: DeepSUVR increased correlation between tracers, and reduced variability in the Aß-negatives. It showed significantly stronger association with cognition, visual reads, neuropathology, and increased longitudinal consistency between studies. DeepSUVR also increased the effect size for detecting small treatment related slowing of amyloid accumulation in the A4 study.

DISCUSSION: DeepSUVR substantially advances Aβ PET quantification, outperforming all standard approaches, which is particularly important for clinical decision making and to detect subtle or early changes in Aβ.

HIGHLIGHTS: Novel artificial intelligence (AI)-method that penalizes biologically implausible longitudinal trajectories, enabling the model to learn standardized uptake value ratios (SUVR) correction factors without requiring longitudinal data at inference time. Improves Centiloid consistency across tracers and studies, significantly enhancing cross-sectional and longitudinal amyloid positron emission tomography (PET) quantification. DeepSUVR-derived Centiloids show stronger associations with cognition, visual reads, and neuropathology. Longitudinal variability is reduced three- to five-fold, enabling more reliable tracking of amyloid accumulation and better detection of treatment effects. Novel reference and target masks derived from DeepSUVR replicate most of the model's performance, offering a practical alternative for integration into existing pipelines.},
}

Humans
*Positron-Emission Tomography/methods
*Alzheimer Disease/diagnostic imaging/metabolism
*Amyloid beta-Peptides/metabolism
Male
*Deep Learning
Female
Aged
*Brain/diagnostic imaging/metabolism
*Neuroimaging/methods
Australia

@article {pmid41669802,
year = {2026},
author = {B Szabo, A and Curot, J and Gérard, F and Rulquin, F and Debs, R and Georges, C and Denuelle, M and Bouloufa, A and Lemesle, B and Péran, P and Thalamas, C and Barbeau, EJ and Pariente, J and Dahan, L and Valton, L},
title = {Refining Detection of Subclinical Epileptiform Activity in Alzheimer's Disease: A Case-Control Study and Call for a Consensus.},
journal = {Annals of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ana.78135},
pmid = {41669802},
issn = {1531-8249},
abstract = {OBJECTIVE: Sleep-predominant network hyperexcitability is increasingly recognized as a potential disease-accelerating comorbidity in Alzheimer's disease (AD). However, its prevalence and risk-factors remain debated, largely due to cohort-specific and methodological differences across studies. In this prospective case-control study, we investigated potential ways of improving detection, from translational approaches focusing on rapid eye movement (REM)-sleep to refined electroencephalogram (EEG) setups and added clinical questionnaires.

METHODS: We recruited 30 patients with early-stage AD without a history of epilepsy and 30 age-matched controls. Participants underwent overnight polysomnography with video-EEG. Interictal epileptic discharges (IEDs) were identified through a structured 3-step review by multiple independent experts using recommended criteria. Neuroanatomic patterns and sleep-related abnormalities were investigated as potential risk factors. Clinical symptoms in favor of epileptic seizures were evaluated through a tailored questionnaire at follow-up.

RESULTS: IEDs were detected in 3 patients (10%) and 1 control (3.33%), a difference not reaching statistical significance (p = 0.612). Most events occurred during non-REM (NREM) sleep. Eight patients (26.67%) reported symptoms compatible with epileptic seizures-one of whom also presented with IEDs. Patients with IEDs or reported symptoms suggestive of potential seizures exhibited more severe sleep-disordered breathing and reduced precuneus volume compared with those without.

INTERPRETATION: Despite efforts to optimize detection accuracy, our findings reveal a lower-than-expected percentage of patients with AD with IEDs, yet support previous findings suggesting that sleep-disordered breathing and specific atrophy patterns could flag at-risk patients, guiding screening in clinical settings. Our findings also favor validation efforts of questionnaires to support the diagnostic process. Finally, we highlight methodological issues in IED detection and call for the re-evaluation and standardization of diagnostic methods and criteria in this population to improve patient care. ANN NEUROL 2026.},
}

@article {pmid41669721,
year = {2025},
author = {Valero, S and Miguel, A and Blazquez-Folch, J and Calm, B and Alegret, M and Solivar, A and Manias, G and Antoniades, A and Angelova, N and Psimaris, D and Segkouli, S and Morera, A and Tantinya, N and Rosende-Roca, M and Cano, A and Fernández, MV and Sanz-Cartagena, P and Gurruchaga, MJ and Tárraga, L and Boada, M and Ruiz, A and Marquié, M and , },
title = {The COMFORTage project: study protocol for the integration of multiple sources towards personalised preventions at Ace Alzheimer Center Barcelona.},
journal = {Frontiers in digital health},
volume = {7},
number = {},
pages = {1633507},
pmid = {41669721},
issn = {2673-253X},
abstract = {INTRODUCTION: Ageing is accompanied by gradual biological and cognitive changes that increase vulnerability to chronic diseases and neurodegenerative conditions. As populations age, dementia prevalence continues to rise, highlighting the need for earlier detection and personalised prevention strategies. Against this background, the COMFORTage project, funded by Horizon Europe, brings together a multidisciplinary consortium across 12 countries to advance innovative, scalable solutions for dementia care. By integrating digital platforms, biomarker research, and precision medicine, COMFORTage seeks to develop artificial intelligence (AI)-driven tools that support more precise and adaptive interventions. Central to this effort are the Virtualized AI-Based Healthcare Platform and Patient Digital Twins, which enable personalised monitoring and decision support. Within this framework, Pilot 3 at Ace Alzheimer Center Barcelona focuses on individuals with mild cognitive impairment and mild Alzheimer's disease dementia, evaluating the effects of cognitive and functional stimulation and contributing multimodal data to optimise the AI platform.

METHODS: Pilot 3 is a randomised, open-label study involving retrospective and prospective datasets. Participants undergo clinical, genetic, neuropsychological, cerebrospinal fluid (CSF) and plasma biomarker assessments, magnetic resonance imaging (MRI), and spontaneous speech analysis. The primary outcomes assess cognitive decline using composite scores from the Neuropsychological Battery used in Ace (NBACE), targeting attention, memory, visuospatial/perceptual functions, executive functions, and language, over a two-year follow-up. Three digital platforms provided by the consortium will be used as cognitive and functional stimulation tools for participants. The intervention's effects on cognitive decline will be evaluated through changes in NBACE composite scores. Secondary objectives include assessing impacts on physical, psychological, social, and functional well-being; examining associations between biological variables and cognitive changes; and analyzing spontaneous speech as a remote, scalable proxy for cognitive status.

DISCUSSION: Findings from Pilot 3 will contribute to COMFORTage's broader mission, offering critical insights into the scalability and real-world implementation of AI-powered dementia care solutions. This integrated approach highlights the potential of precision medicine and advanced digital tools to elevate global standards in dementia management.

CLINICAL TRIAL REGISTRATION: identifier NCT07031167.},
}

@article {pmid41669460,
year = {2026},
author = {Feng, J and Ng, KP and Wang, H and Yao, T and Su, Q and Ba, M and Wang, G},
title = {Alzheimer's disease prediction algorithm based on hippocampal longitudinal hybrid morphological features.},
journal = {Quantitative imaging in medicine and surgery},
volume = {16},
number = {2},
pages = {170},
pmid = {41669460},
issn = {2223-4292},
abstract = {BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline; this decline is closely linked to hippocampal morphological changes observed in structural magnetic resonance imaging (MRI). However, the existing AD prediction models have not fully explored the spatiotemporal correlation of hippocampal morphological features. To address this limitation, this study aims to develop a longitudinal prediction framework that captures both the temporal evolution and spatial distribution of hippocampal morphological alterations.

METHODS: In this paper, we propose a novel deep learning framework for predicting the clinical progression of AD, which consists of a multi-view feature fusion convolutional network (M-FCN) and a bidirectional gated recurrent unit (Bi-GRU). The proposed M-FCN is based on the three-dimensional (3D) topological structure features of the hippocampus that introduces thickness features and heat kernel signature (HKS) to encode hippocampal morphological atrophy features. We utilize these features to construct a deep 3D hippocampus features description system for capturing the micro and macro structural changes of hippocampus. Hence, the task driven attention mechanism for prediction can effectively identify significant morphological changes caused by AD. The Bi-GRU module identifies inter sequence patterns and studies the temporal correlation between longitudinal features of hippocampus.

RESULTS: The proposed method was evaluated using longitudinal T1-weighted MRI data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) (n=221). Compared with the existing AD prediction models, the correspondence between AD-related structural changes and clinical neurodegeneration indicators can be more accurately captured by our proposed deep learning model. The predictive performance was evaluated using root mean square error (RMSE), correlation coefficient (CC), and 95% confidence interval (CI). For the prediction of Mini-Mental State Examination (MMSE) scores, the model achieved a RMSE of 2.34 (95% CI: 2.27-2.45, CC =0.72) at M18, 2.58 (95% CI: 2.52-2.64, CC =0.77) at M24, and 2.60 (95% CI: 2.54-2.66, CC =0.83) at M36.

CONCLUSIONS: These results highlight the effectiveness of the proposed model in leveraging the spatiotemporal correlation of hippocampal morphology to provide high accuracy and reliable predictions.},
}

@article {pmid41669458,
year = {2026},
author = {Wei, L and Zhang, W and Lu, J and Liu, D and Li, X and Liu, G and Yang, H and Wang, H and Zhu, Z and Li, X and Zhang, X and Bai, B and Zhang, B},
title = {Neuropathological links between plasma p-Tau 181, white matter hyperintensity, and structural brain changes in aging.},
journal = {Quantitative imaging in medicine and surgery},
volume = {16},
number = {2},
pages = {150},
pmid = {41669458},
issn = {2223-4292},
abstract = {BACKGROUND: White matter hyperintensity (WMH) has been reported to be associated with brain structure changes and Alzheimer's disease (AD) pathology in the aging process. This study sought to explore the underlying mechanisms linking cerebrovascular pathology, structural brain changes, and AD pathology in the aging process.

METHODS: The routine magnetic resonance images of 218 cognitively normal elderly individuals who underwent venous blood sampling were retrospectively collected. The Fazekas score was used to stratify the cohort into mild (Fazekas scores of 0-1, n=113) and severe (Fazekas scores of 2-3, n=105) WMH groups. All the three-dimensional (3D) T1-weighted (T1W) images, including the original 3D T1W images and the 3D T1W images reconstructed from two-dimensional (2D) diagnostic images, were processed with FreeSurfer to determine the cortical thickness and subcortical nucleus volumes. The plasma amyloid-beta (Aβ)42 and phosphorylated tau (p-Tau) 181 levels were measured by enzyme-linked immunosorbent assay (ELISA). The cerebral small vessel disease (CSVD)-related imaging markers were assessed manually. Group comparisons of brain structures were performed using general linear models (GLMs). Partial correlation analyses were conducted to assess the associations between plasma Aβ42/p-Tau 181 and the subcortical volumes. A mediation analysis was conducted to evaluate the mediating role of the WMH burden in the relationship between plasma biomarker levels and brain structure.

RESULTS: The participants with severe WMH were older (P<0.001) and exhibited higher plasma p-Tau 181 (P<0.001) than those in the mild WMH group, but no significant difference in plasma Aβ42 was found (P=0.065). Based on the original 3D T1W images only, the left caudate nucleus (P=0.042) was enlarged in the participants with severe WMH. Based on all the 3D T1W images, the plasma p-Tau 181 levels were found to be positively correlated with the Fazekas scores (r=0.165, P=0.015). A significant interaction was observed between age and groups in terms of the left caudate volume (β=1.288, P=0.047). More importantly, the Fazekas scores were found to partially mediate the relationship between the p-Tau 181 levels and left caudate volumes (indirect effect =1.761, P=0.035), accounting for 23.0% of the total effect.

CONCLUSIONS: Severe WMH is associated with caudate nucleus enlargement. WMH may partially mediate the association between elevated plasma p-Tau 181 and caudate nucleus enlargement, suggesting a mixed pathology in the aging process of the brain, and highlighting the importance of early vascular risk control.},
}

@article {pmid41669119,
year = {2026},
author = {Coe, NB and Miller, KEM and Sun, C and Taggert, E and Gross, AL and Jones, RN and Felix, C and Albert, MS and Rebok, GW and Marsiske, M and Ball, KK and Willis, SL},
title = {Impact of cognitive training on claims-based diagnosed dementia over 20 years: evidence from the ACTIVE study.},
journal = {Alzheimer's & dementia (New York, N. Y.)},
volume = {12},
number = {1},
pages = {e70197},
pmid = {41669119},
issn = {2352-8737},
abstract = {INTRODUCTION: The very long-term effect of cognitive training on the risk of Alzheimer's disease and related dementias (ADRD) is unknown.

METHODS: This study links data from the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study (a four-arm randomized controlled trial of cognitive training in a large, diverse sample) to Medicare claims (1999 to 2019). Inclusion in the analyses required being enrolled in traditional Medicare at baseline (n = 2021). ADRD was measured with the Chronic Conditions Warehouse algorithm.

RESULTS: Participants randomized to the speed-training arm who completed one or more booster sessions had a significantly lower risk of diagnosed ADRD (hazard ratio [HR]: 0.75, 95% confidence interval [CI]: 0.59, 0.95), while speed-trained participants with no booster training did not have a lower risk of diagnosed ADRD (HR: 1.01, 95% CI: 0.81, 1.27). There was no main effect of memory or reasoning training on risk of ADRD.

CONCLUSIONS: Cognitive training involving speed of cognitive processing has the potential to delay the diagnosis of ADRD.

HIGHLIGHTS: The ACTIVE study (a four-arm randomized controlled trial of cognitive training in a large, representative sample) reports that the speed intervention arm of the study showed a reduced likelihood of being diagnosed with ADRD over a 20-year follow-up period.No prior cognitive training intervention has been shown to reduce risk of ADRD over a 20-year period.Cognitive training involving speeded, dual attention, adaptive tasks has the potential to delay the diagnosis of ADRD.},
}

@article {pmid41669118,
year = {2026},
author = {Romic, E and Karlsson, I and Karalija, N and Adolfsson, AN and Adolfsson, R and Kauppi, K},
title = {Pathway-based polygenic risk of Alzheimer's disease highlights immune genes in cognitive decline.},
journal = {Alzheimer's & dementia (New York, N. Y.)},
volume = {12},
number = {1},
pages = {e70209},
pmid = {41669118},
issn = {2352-8737},
abstract = {INTRODUCTION: Alzheimer's disease (AD) is a genetically heterogeneous disease, with various genetic variants potentially influencing disease mechanisms differently. Pathway-based polygenic risk scores (p-PRS) can be used to examine how groups of risk genes with similar biological functions impact disease-related endophenotypes such as cognitive decline. potentially aiding in differentiating pre-clinical dementia from normal age-related cognitive decline.

METHODS: Data from 1,737 participants (53.5% female) from the Betula study were analyzed. AD-weighted p-PRS were calculated for five AD-related pathways: immune response, tau, cholesterol, protein-lipid, and amyloid. The p-PRS were tested for associations with all-cause dementia risk (n = 315 cases), with follow-up analyses restricted to AD (n = 168) or vascular dementia (VD) (n = 110), in comparison to a genome-wide (gw) PRS. Linear mixed effect models were used to examine the same genetic predictors in relation to cognitive decline in subsequently demented and non-demented.

RESULTS: All-cause dementia risk was significantly predicted by the gw- and immune PRS. Hazard ratios for gw-, immune-, tau-, cholesterol-, and amyloid p-PRS were larger for prediction of AD risk and smaller for VD risk relative to all-cause dementia, while the opposite was seen for the protein-lipid p-PRS. Cognitive decline was stronger associated with the immune p-PRS than the gw-PRS, and this effect was driven by participants that remained non-demented (linear age-effects). Amyloid p-PRS showed accelerated age-effect at the oldest age in both non-demented and subsequently demented.

DISCUSSION: Our results show that AD-weighted p-PRS have differential roles on dementia risk and cognitive decline. Specifically, results suggest a broad role of immune p-PRS in both age-related cognitive decline and dementia risk, while amyloid p-PRS influences AD risk and pre-clinical cognitive decline, and protein-lipid p-PRS does not influence AD risk nor cognitive decline but show a potential role in VD. Results are of value for development of precision medicine based on genetic risk profiling.

HIGHLIGHTS: All-cause dementia and Alzheimer's disease (AD) risk is strongest predicted by apolipoprotein E (APOE) ε4 and global polygenic risk scores (PRS).Cognitive decline is stronger predicted by immune pathway-based PRS (p-PRS) relative to global PRS.Effect of APOE ε4 on cognitive decline is driven by pre-clinical dementia.Immune p-PRS predicts cognitive decline unrelated to subsequent dementia.Protein-lipid p-PRS may have a stronger role in vascular dementia than AD.},
}

@article {pmid41669094,
year = {2026},
author = {Kamal, F and Moqadam, R and Morrison, C and Dadar, M},
title = {Intersecting vulnerabilities: race, depression, and white matter hypointensity burden in aging.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {1},
pages = {e70252},
pmid = {41669094},
issn = {2352-8729},
abstract = {INTRODUCTION: White matter hypointensities (WMHs) are associated with cognitive decline and dementia. However, it remains unknown how race, ethnicity, and depression influence WMHs. This study examined the interactive effects of race/ethnicity and depression on WMHs and cognition.

METHODS: Data from the National Alzheimer's Coordinating Center included 2411 older adults (773 Whites with and 1360 Whites without depression and 89 Blacks with and 189 Blacks without depression). Linear regressions assessed WMH differences across race/ethnicity and depression groups and the associations between WMH burden and cognition.

RESULTS: Black older adults with depression showed greater global and regional WMH burden than Black older adults without depression, and depression significantly influenced the relationship between WMHs and cognitive impairment. Similar results were observed for Hispanic older adults; however, these findings were not observed in White older adults.

DISCUSSION: These findings suggest that race and depression may jointly influence cerebrovascular disease burden as well as its associations with cognition in aging and dementia.},
}

@article {pmid41669092,
year = {2026},
author = {Kpelle, L and Bockarie, A and Antwi, MH and Osei, GN and Donkor, DM and Brodie-Mends, D and Adu, AM and Simpong, DL},
title = {Population disparities in Alzheimer's disease: A systematic review of fluid and neuroimaging biomarkers.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {1},
pages = {e70263},
pmid = {41669092},
issn = {2352-8729},
abstract = {Alzheimer's disease manifests differently across ancestral groups, with African populations showing distinct fluid biomarker levels, neuroimaging patterns, and post mortem pathology. These differences may compromise diagnostic accuracy and exacerbate health disparities. This systematic review, examined studies published from 2015 to 2025 assessing amyloid-β and tau via fluid assays and neuroimaging. Findings reveal ancestry-linked variation where African populations exhibit lower cerebrospinal fluid/plasma Aβ42/Aβ40 and p-tau181 ratios, with neuroimaging showing broadly similar reduced positron emission tomography patterns but slightly elevated amyloid and reduced tau signals. Limited post mortem data suggest reduced plaque and tangle densities despite comparable dementia severity. Genetic, environmental, and sociocultural factors contribute to these disparities. Diagnostic thresholds derived from non-African cohorts risk underdiagnosing AD in African individuals. There is an urgent need to recalibrate and validate biomarker protocols to ensure equitable and accurate dementia diagnosis across diverse populations.},
}

@article {pmid41669080,
year = {2026},
author = {Shimizu, S and Kasai, S and Suzuki, C and Kon, T and Suganuma, H and Suzuki, S and Murashita, K and Nakaji, S and Ihara, K and Tomiyama, M and Itoh, K},
title = {Efficacy of 42-month oral administration of glucoraphanin in preventing cognitive decline in individuals at elevated risk of dementia, including those with mild cognitive impairment: a randomized, double-blind, placebo-controlled pilot study.},
journal = {Frontiers in nutrition},
volume = {13},
number = {},
pages = {1740494},
pmid = {41669080},
issn = {2296-861X},
abstract = {BACKGROUND: Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that regulates cellular defense mechanisms and has been proposed as a therapeutic target for Alzheimer's disease (AD). Preclinical studies suggest that long-term oral administration of glucoraphanin (GLR), a natural Nrf2 activator, mitigates age-related cognitive decline in animal models.

OBJECTIVE: This study evaluated the long-term efficacy of GLR supplementation on cognitive function in older adults at an elevated risk for AD, including those with mild cognitive impairment (MCI).

METHODS: In a 42-month randomized, double-blind, placebo-controlled trial, 26 participants aged 63-90 years with memory impairment were randomly assigned to receive either 30 mg/day of GLR (n = 13) or placebo (n = 12). The primary outcome was the change in Memory Performance Index (MPI) scores from the MCI Screen. Secondary outcomes included conversion/reversion rates between normal cognition and MCI.

RESULTS: Ten participants in the GLR group and nine participants in the placebo group completed the trial. Analysis using a Linear Mixed Model (LMM) across the entire study period revealed a significant group by time-point interaction for MPI scores, with the GLR group showing a significantly greater improvement in MPI scores compared to the placebo (p = 0.012). No significant group difference was observed in the initial 6 months, but a marginal difference in favor of GLR appeared in the later phase (30 and 42 months), including the 42-month endpoint (p = 0.079). Conversion/reversion rates were not significantly different. The GLR group demonstrated superior performance on immediate recall and delayed free recall tests (p < 0.001 and p = 0.012, respectively). MCI participants showed a greater MPI improvement with GLR (p = 0.029). No severe adverse events related to the intervention were reported.

CONCLUSION: Long-term GLR supplementation may help preserve cognitive function in individuals at elevated risk for AD, particularly those with MCI. Larger trials are warranted to confirm efficacy and clarify underlying mechanisms.},
}

@article {pmid41668840,
year = {2026},
author = {Selingardi, PML and Friedlaender, CV and Zibetti, MR and Paciência, GC and Caramelli, P and Yassuda, MS},
title = {Systematic review of Free and Cued Selective Reminding Test with Immediate Recall (FCSRT-IR) studies: normative data, clinical validity, and correlations with biomarkers.},
journal = {Dementia & neuropsychologia},
volume = {20},
number = {},
pages = {e20250399},
pmid = {41668840},
issn = {1980-5764},
abstract = {The Free and Cued Selective Reminding Test with Immediate Recall (FCSRT-IR), developed by Grober and Buschke, is widely used to assess episodic memory and detect impairments, particularly in Alzheimer's disease (AD). Recommended by the International Working Group (IWG) for early diagnosis, no prior review has synthesized its findings. This study reviewed articles on norms, clinical validity, and correlations with neuropathological biomarkers. Sixty-four studies were selected out of 728, covering normative data, clinical validation, and biomarker associations. The FCSRT-IR has normative data from seven countries and shows high diagnostic accuracy for mild cognitive impairment (MCI) and dementia, especially AD. In 20 studies, test scores significantly correlated with AD biomarkers. Thus, the FCSRT-IR supports early identification of episodic memory deficits, proving to be a valuable neuropsychological assessment tool.},
}

@article {pmid41668808,
year = {2025},
author = {Bianco, LS and Nicoliche, T and Corrêa-Neto, NF and Lanaro, R and Caetano, AL and Prado, CM and Ureshino, RP and Tibério, IFLC and Righetti, RF and Stilhano, RS and Linardi, A},
title = {Anti-inflammatory effects of Banisteriopsis caapi and beta-carbolines in neuronal cells: potential implications for neuro-COVID.},
journal = {Frontiers in pharmacology},
volume = {16},
number = {},
pages = {1703727},
pmid = {41668808},
issn = {1663-9812},
abstract = {BACKGROUND: Neuroinflammation plays a central role in neurodegenerative diseases such as Alzheimer's and Parkinson's, along with depression, anxiety, and infectious diseases including COVID-19. Harmine and harmaline, β-carboline alkaloids from Banisteriopsis caapi, exhibit immunomodulatory, anti-inflammatory, and neuroprotective properties. In this study, we aimed not only to investigate the anti-inflammatory and neuroprotective effects of β-carbolines and B. caapi extract on a lipopolysaccharide (LPS)-induced neuroinflammation model using SH-SY5Y cells and their impact on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor expression but also to compare cytokine levels in plasma from intensive care unit (ICU) and non-ICU COVID-19 patients, thereby providing clinical context for the inflammatory response.

METHODS: SH-SY5Y cells were treated with LPS and incubated with harmine, harmaline, or B. caapi extract. Cell viability was assessed using the MTT assay. Cytokine expression was quantified by ELISA, and receptor gene expression was analyzed using RT-qPCR. Plasma was obtained from the Hospital das Clínicas of the University of São Paulo Medical School (HCFMUSP) biobank.

RESULTS: IL-6 was high in ICU patients; LPS increased IL-6 and TNF-α cytokine levels in cells, whereas harmine and harmaline significantly reduced both cytokines. B. caapi extract decreased LPS-induced NF-κB and TNF-α but did not affect IL-6. Harmine also reduced NF-κB expression. None of the treatments altered TMPRSS11D or furin, and harmaline showed no effect on ACE2. In contrast, the extract upregulated ACE2, whereas harmine induced a modest increase. Only harmine and harmaline reduced TMPRSS2 expression.

CONCLUSION: β-carbolines and B. caapi extract attenuate LPS-induced cytokine production in SH-SY5Y cells, supporting their anti-inflammatory and neuroprotective potential. The extract and β-carbolines also modulate ACE2 and TMPRSS2 expressions, suggesting relevance to mechanisms associated with neuro-COVID.},
}

@article {pmid41668753,
year = {2026},
author = {Giff, AE and Wruble Clark, M and Bhattacharyya, S and Sage, PT and Madore, B and Guenette, JP and Miyawaki, EK},
title = {Deep cervical lymph node analysis in central nervous system inflammatory disease.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1747114},
pmid = {41668753},
issn = {1664-3224},
mesh = {Humans ; *Lymph Nodes/immunology/pathology ; Animals ; *Neuroinflammatory Diseases/immunology ; Glymphatic System/immunology ; },
abstract = {A previously espoused notion that the brain is an immune-privileged organ has been challenged by evidence of bidirectional communication between the central nervous system and the periphery. A well-described "glymphatic" system in the brain and the meningeal lymphatic system serve as conduits through which antigens, immune cells, and metabolic waste travel from the brain to the deep cervical lymph nodes. These nodes, which are more than passive drainage points, serve as locales where dendritic cells, T cells, and B cells interact with central nervous system-derived signals and modulate immune responses that can influence the brain itself. Disruption of clearance mechanisms to deep cervical nodes-due to intracranial vascular disease, aging, poor sleep, chronic inflammation, or other etiologies-may lead to immune dysregulation. Abnormalities in lymphatic drainage can also alter the presentation of antigens from the central nervous system, affect lymphocyte trafficking, and contribute to the aggregation of proteins like β-amyloid, tau, and α-synuclein. This review synthesizes current knowledge on glymphatic and meningeal lymphatic anatomy and function, highlights how impaired drainage contributes to disorders including multiple sclerosis, Alzheimer disease, and Parkinson disease, and discusses the emerging role of deep cervical lymph node imaging and immunophenotyping in assessing neuroinflammation. Finally, we consider how modulation of meningeal lymphatic and nodal function, through pharmacologic or physical interventions, may impair or restore drainage and alter the course of disease in various ways. The integration of advanced imaging with immunological analysis ultimately may enhance the diagnosis, monitoring, and treatment of neuroinflammatory and neurodegenerative diseases. We propose that deep cervical lymph nodes represent an understudied locale, and, potentially, a therapeutic target for peripheral interventions to influence brain disease trajectories.},
}

Humans
*Lymph Nodes/immunology/pathology
Animals
*Neuroinflammatory Diseases/immunology
Glymphatic System/immunology

@article {pmid41668745,
year = {2026},
author = {Li, D and Qian, Y and Wan, L and Zhang, K and Song, L and Zhang, X and Yang, X},
title = {Lipoprotein-associated phospholipase A2 (Lp-PLA2): a key hub linking lipid metabolism and immune inflammation.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1705738},
pmid = {41668745},
issn = {1664-3224},
mesh = {Humans ; *1-Alkyl-2-acetylglycerophosphocholine Esterase/metabolism/immunology ; *Lipid Metabolism/immunology ; *Inflammation/immunology/metabolism ; Animals ; Lipoproteins, LDL/metabolism ; },
abstract = {Lipoprotein-associated phospholipase A2 (Lp-PLA2), also known as phospholipase A2 group VII (PLA2G7), is an enzyme that serves as a critical nexus between lipid metabolism and immune regulation. It exhibits dual and context-dependent functions by hydrolyzing platelet-activating factor (PAF) and oxidized low-density lipoprotein (oxLDL). The degradation of PAF results in the production of Lysoplatelet activating factor (LysoPAF), which attenuates inflammatory signaling. In contrast, the hydrolysis of oxLDL generates lysophosphatidylcholine (LysoPC) and oxidized fatty acids (oxFA), which exacerbate vascular inflammation, promote macrophage M1 polarization, and inhibit CD8[+] T cell activity. Through these pathways, Lp-PLA2 is implicated in a range of diseases, including atherosclerosis, diabetes, Alzheimer's disease, cancer, autoimmune disorders, and inflammation associated with infections. Despite extensive pharmacological interventions targeting this enzyme, clinical outcomes have been inconsistent, reflecting its complex roles across various pathophysiological contexts. This review synthesizes current knowledge on the mechanisms of Lp-PLA2, its associations with diseases, and its therapeutic implications, emphasizing its potential as both a biomarker and a therapeutic target at the intersection of lipid metabolism and immune response.},
}

Humans
*1-Alkyl-2-acetylglycerophosphocholine Esterase/metabolism/immunology
*Lipid Metabolism/immunology
*Inflammation/immunology/metabolism
Animals
Lipoproteins, LDL/metabolism

@article {pmid41668551,
year = {2026},
author = {Gao, C and Li, Y and Zhou, B and Liu, Y and Hao, MQ and Sun, H and Jin, Z and Li, LL and Yang, XF and Guo, XL and Yin, Y},
title = {The application of exosomes derived by mesenchymal stem cell from different tissues in the management of Alzheimer's disease.},
journal = {Nanomedicine (London, England)},
volume = {},
number = {},
pages = {1-13},
doi = {10.1080/17435889.2026.2629030},
pmid = {41668551},
issn = {1748-6963},
abstract = {With the intensifying global trend of population aging, the treatment of Alzheimer's disease (AD) faces significant challenges. Current therapeutic approaches can only temporarily alleviate symptoms without halting or reversing disease progression. Numerous studies on mesenchymal stem cell-derived exosomes (MSC-Exos) suggest that, compared to stem cell therapy, MSC-Exos offer considerable advantages in the treatment of AD. This review examines the various mechanisms by which exosomes produced from MSCs function as therapeutic agents for AD. Additionally, it provides a concise overview of the research conducted on MSC-Exos for AD, categorized by tissue source. The text also provides an account of the ongoing clinical trials involving MSC-Exos and examines their benefits, drawbacks, and potential avenues for future research.},
}

@article {pmid41668547,
year = {2026},
author = {Zhang, Y and Wang, J and Yuan, J and Li, S and Sun, Y},
title = {FA-2-b-β modulates HMGB1/NF-κB/NLRP3 signaling to alleviate neuroinflammation in Alzheimer's disease.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261418300},
doi = {10.1177/13872877261418300},
pmid = {41668547},
issn = {1875-8908},
abstract = {BackgroundFA-2-b-β, an extract derived from traditional Chinese medicine (TCM), has been suggested as a potential neuroprotective agent.ObjectiveThis study aimed to elucidate its role in modulating HMGB1-mediated inflammation and pyroptosis in Alzheimer's disease (AD), with a particular emphasis on the interaction between FA-2-b-β and HMGB1.MethodsAD cell and animal models were used to examine the effect of FA-2-b-β on HMGB1/NF-κB/NLRP3 signaling pathway. Protein expression levels were detected by western blotting, and enzyme-linked immunosorbent assay (ELISA), respectively. Immunofluorescence staining was performed to determine the cellular localization of key proteins. The role of HMGB1 in amyloid-β (Aβ)-induced neuroinflammation and pyroptosis was examined through siRNA-mediated HMGB1 knockdown. Behavioral tests were conducted in AD animal models to evaluate cognitive improvements following FA-2-b-β treatment.ResultsIn cellular models, FA-2-b-β significantly suppressed Aβ-induced overexpression HMGB1 and inhibited the activation of NF-κB, which consequently led to a reduction in the formation of the NLRP3 inflammasome. This suppression resulted in decreased of activation caspase-1 and lower levels of IL-1β and IL-18, thereby alleviating pyroptosis and neuroinflammation. The knockdown of HMGB1 further corroborated its role in mediating Aβ-induced inflammatory responses. In AD animal models, treatment with FA-2-b-β attenuated neuroinflammation, preserved neuronal integrity, and enhanced cognitive function.ConclusionsFA-2-b-β exhibits a capacity to modulate the HMGB1/NF-κB/NLRP3 signaling pathway, thereby mitigating neuroinflammation and pyroptosis, highlighting its potential as a therapeutic intervention for AD.},
}

@article {pmid41668529,
year = {2026},
author = {Wang, W and Chen, Y and Xiong, Z and Wang, Z and Ye, W and Li, X},
title = {Donepezil Research in Cognitive Impairment: A Bibliometric and Scientometric Analysis of Global Trends and Pharmacological Perspectives.},
journal = {Brain and behavior},
volume = {16},
number = {2},
pages = {e71251},
doi = {10.1002/brb3.71251},
pmid = {41668529},
issn = {2162-3279},
support = {//Neurosurgery First-class Discipline Funding Project of the Second Affiliated Hospital of Harbin Medical University/ ; },
mesh = {*Donepezil/therapeutic use/pharmacology ; Humans ; *Bibliometrics ; *Cognitive Dysfunction/drug therapy ; Alzheimer Disease/drug therapy ; Cholinesterase Inhibitors/therapeutic use/pharmacology ; *Nootropic Agents/therapeutic use/pharmacology ; Biomedical Research ; },
abstract = {BACKGROUND: Cognitive impairment (CI) greatly affects global health and quality of life. Donepezil, a widely used treatment for CI, particularly in Alzheimer's disease, has been extensively studied; however, a comprehensive bibliometric analysis summarizing global research trends remains limited.

METHODS: Relevant English-language articles and reviews published between 2000 and 2025 were retrieved from the Web of Science Core Collection. CiteSpace and VOSviewer were employed to analyze publication trends, collaborative networks, journal distribution, co-citation patterns, and keyword co-occurrence.

RESULTS: A total of 1907 publications were identified. The United States led in both output and citation impact, with the University of Toronto emerging as the most influential institution. The U.S. Department of Health and Human Services provided the greatest funding support. The Journal of Alzheimer's Disease was the primary publishing outlet, and Etsuro Mori was the most prolific and influential author. Keyword analysis revealed "Donepezil," "Alzheimer's disease," and "Mild cognitive impairment" as dominant terms. Recent hotspots-such as "acetylcholinesterase," "oxidative stress," "neuroinflammation," "tau protein," and "mechanism"-reflect a shift toward mechanistic and preclinical research.

CONCLUSION: Research on donepezil for CI has shown consistent growth, evolving from clinical application toward mechanistic exploration and disease modification. Future studies are expected to focus on individualized therapy, combination strategies, and underexplored CI subtypes, aiming to enhance the therapeutic potential and clinical value of donepezil.},
}

*Donepezil/therapeutic use/pharmacology
Humans
*Bibliometrics
*Cognitive Dysfunction/drug therapy
Alzheimer Disease/drug therapy
Cholinesterase Inhibitors/therapeutic use/pharmacology
*Nootropic Agents/therapeutic use/pharmacology
Biomedical Research

@article {pmid41668525,
year = {2026},
author = {Gifford, KA and Rong, J and Schramm, E and Zhang, Y and Pathiravasan, CH and Benjamin, EJ and Lin, H and Liu, C and Au, R and Libon, DJ and Murabito, JM},
title = {Digital Stroop Test as a neurocognitive marker in a community-based sample of older adults: Data from the Framingham Heart Study.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877251415030},
doi = {10.1177/13872877251415030},
pmid = {41668525},
issn = {1875-8908},
abstract = {BackgroundDigital cognitive testing allows for assessment of more granular aspects of cognition that may enhance the ability to detect cognitive decline and Alzheimer's disease earlier.ObjectiveTo assess cognition using a smartphone-based Stroop Task in older adults.MethodsThe smartphone-based Stroop Task consisted of four subtests including two with minimal cognitive demand, i.e., color matching (subtest 1) and color-word matching (subtest 2), and two with greater cognitive demand i.e., inhibition (subtest 3); and inhibition/switching (subtest 4). Each subtest consisted of five trials. Repeated measures ANOVA were conducted to examine mean completion times within and between the four test conditions. Completion times were also compared to traditional neuropsychological tests.ResultsAmong 478 iPhone users, 429 (89.7%) used the app-based Stroop Test (mean age 73.5 years (6.4), 58% female, 87% non-Hispanic White, mean MMSE score 28.75 ± 1.4). Error-free performance occurred in 395 participants on subtest 1, 404 on subtest 2, 320 on subtest 3, and 183 on subtest 4. Mean completion times differed between the four subtests (all p < 0.0001) with faster subtest 2 completion (1.45 to 1.19 s across the five trials) and slower subtest 4 completion (2.95 to 2.75 s across the 5 trials) than the other subtests. Completion times were positively associated with paper/pencil measures of processing speed but negatively associated with measures of episodic and working memory and language.ConclusionsWe demonstrate the feasibility and construct validity of administering a fully self-administered smartphone-based Stroop cognitive test in older adults completed outside a clinical setting.},
}

@article {pmid41668484,
year = {2026},
author = {Wang, Q},
title = {[Current status and future perspectives on age-related hearing loss and cognitive impairment].},
journal = {Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery},
volume = {40},
number = {3},
pages = {220-225},
doi = {10.13201/j.issn.2096-7993.2026.03.002},
pmid = {41668484},
issn = {2096-7993},
mesh = {Humans ; Aged ; *Presbycusis ; *Cognitive Dysfunction ; *Cognition Disorders ; *Hearing Loss ; Aging ; },
abstract = {Objective:Age-related hearing loss（ARHL） is one of the most common sensory degenerative disorders in the elderly, characterized by high prevalence, insidious onset, and progressive deterioration. Recent studies indicate that ARHL not only impairs communication and quality of life in older adults, but is also significantly associated with the development of cognitive impairment and Alzheimer's disease. However, its underlying pathogenesis remains incompletely understood, and the relationship between clinical phenotypes of ARHL and cognitive decline has yet to be clearly defined. ARHL occupies a pivotal position in geriatric health management and in the prevention of neurodegenerative diseases, yet it has not been systematically conceptualized or mechanistically examined. In this review, we summarize the current research progress on ARHL and cognitive impairment, analyze possible mechanisms linking the two conditions, evaluate the potential cognitive protective effects of hearing interventions, and propose priority directions for future research and clinical practice. With advances in multidisciplinary collaboration and technological innovation, the prevention and treatment of ARHL are expected to enter a new era of greater precision and efficiency, offering novel opportunities to reduce the risk of cognitive impairment and improve overall health in older populations.},
}

Humans
Aged
*Presbycusis
*Cognitive Dysfunction
*Cognition Disorders
*Hearing Loss
Aging

@article {pmid41668347,
year = {2026},
author = {Giambartolomei, GH and Iribarren, P and Pasquini, LA and Peluffo, H},
title = {Microglia at the Forefront: New Insights From the Glial Club South Cone Meeting 2025.},
journal = {Journal of neurochemistry},
volume = {170},
number = {2},
pages = {e70384},
doi = {10.1111/jnc.70384},
pmid = {41668347},
issn = {1471-4159},
support = {PICT 2019-1178//the Agencia Nacional de Promoción Científica y Tecnológica/ ; PICT 2019-0839//the Argentine Agency for the Promotion of Science and Technology/ ; PIP 2021-2023 GI//CONICET/ ; UBACYT-20020170100285BA//the University of Buenos Aires/ ; 2022-1236//the Pasqual Maragall Foundation/ ; PID2021-123272OB-I00//MICIU/AEI/ ; PID2024-156165NB-I00//MICIU/AEI/ ; },
mesh = {Humans ; *Microglia/metabolism/immunology ; Animals ; Phagocytosis/physiology ; Autophagy/physiology ; Congresses as Topic/trends ; Alzheimer Disease/immunology/metabolism ; },
abstract = {Microglia are the primary innate immune cells of the central nervous system and act as dynamic regulators of neural development, homeostasis, and response to injury. This review summarizes key discussions from the Glial Club South Cone Meeting 2025, focusing on (i) mechanisms and regulation of microglial phagocytosis and its dual role in tissue repair and neurodegeneration, (ii) the emerging immunometabolic and neuroprotective functions of the lipid-sensing receptor CD300f in aging and Alzheimer's disease models, and (iii) the context-dependent roles of autophagy in microglial activation, inflammation control and proteostasis. We highlight how phagocytic signaling (IFN, IL-6, "eat-me," "don't-eat-me" cues), immune receptors and epigenetic regulation shape microglial states and function. Translational implications are discussed, including strategies to preserve beneficial microglial functions while limiting detrimental phagoptotic and pro-inflammatory responses. Identifying receptor-specific ligands, clarifying causal roles of phagocytosis in neurodegeneration, and dissecting autophagy-dependent quality-control pathways emerge as priority areas for future research.},
}

Humans
*Microglia/metabolism/immunology
Animals
Phagocytosis/physiology
Autophagy/physiology
Congresses as Topic/trends
Alzheimer Disease/immunology/metabolism

@article {pmid41668286,
year = {2026},
author = {Fikse, E and Anderson, F and Cho, S and Landry, J and Carloni, E and Biggs, K and Paul, K and Daley, T and Chang, TY and Kettenbach, A and Havrda, MC},
title = {Suppression of haptoglobin and loss of striatal neurons in mice chronically exposed to chlorpyrifos contaminated drinking water.},
journal = {Toxicological sciences : an official journal of the Society of Toxicology},
volume = {},
number = {},
pages = {},
doi = {10.1093/toxsci/kfag012},
pmid = {41668286},
issn = {1096-0929},
abstract = {Exposure to agricultural chemicals is a risk factor for neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD). Chlorpyrifos (CPF) is an organophosphate insecticide widely used in agricultural and occupational settings. Epidemiological studies have associated CPF exposure with developmental impairments and an increased risk of AD and PD. Experimental characterization of the impact of chronic, systemic CPF exposure is essential for understanding how organophosphates actually influence disease risk. Multiple studies have assessed the effects of gestational exposure to CPF in preclinical models. To model exposure faced by adults, we administered CPF-contaminated drinking water to mice from 6 to 22 months of age. This chronic exposure led to systemic effects, including reduced levels of the acute-phase protein haptoglobin (HTP) in both plasma and liver. Notably, the combination of aging and CPF exposure resulted in astrogliosis in the hippocampus and striatum, as well as neuronal loss in the striatum, primarily due to the loss of GAD65/67-immunoreactive interneurons. Having identified CPF-driven suppression of HPT in peripheral tissues, we examined HPT expression in brain tissues. We readily detected HPT expression in brain microglia. We then cultivated primary microglia and found that CPF exposure decreased HPT secretion in vitro. These findings indicate systemic and neurotoxic effects resulting from adult exposure to CPF-contaminated water.},
}

@article {pmid41668187,
year = {2026},
author = {Chai, GS and Gao, TL and Bi, SG and Mao, YM and Yang, L and Wang, FZ and Chen, J and Wu, JJ and Gong, J and Geng, S and Yuan, JQ and Zhang, KY and Yi, HY and Lan, ZC and Nie, YJ and Yu, H},
title = {Aerobic exercise facilitates p300 nuclear translocation via ADRB2-AMPKα signaling, leading to enhanced histone acetylation and mitigation of cognitive decline in APP/PS1 mice.},
journal = {Alzheimer's research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13195-026-01983-z},
pmid = {41668187},
issn = {1758-9193},
support = {82571630; 81601121//National Natural Science Foundation of China/ ; 82401671//National Natural Science Foundation of China/ ; BK20211238//the Natural Science Foundation of Jiangsu Province/ ; BK20231050//the Natural Science Foundation of Jiangsu Province/ ; 2020M651491//China Postdoctoral Science Foundation/ ; 2020Z037//Jiangsu Province Postdoctoral Science Foundation/ ; JSTJ-2024-370//Youth Talent Support Project of Jiangsu Province for Science and Technology/ ; YXXK20240926003//Medical Development Foundation of Jiangnan University/ ; JUSRP123070//the Fundamental Research Funds for the Central Universities/ ; },
abstract = {BACKGROUND: Physical activity (PA) is strongly associated with enhanced cognitive resilience and a lower risk of Alzheimer's disease (AD) in the aging population. However, the molecular mechanisms linking exercise-induced neuroprotection to epigenetic remodeling remain poorly defined.

METHODS: A total of 1,511 participants from the National Health and Nutrition Examination Survey (NHANES) 2013-2014 cohort were included to assess the association between PA and cognitive performance. Mendelian randomization (MR) analysis was further employed to infer the causal relationship between PA and the risk of various dementias. Differential gene enrichment analysis was performed using the Gene Expression Omnibus (GEO) dataset (GSE110298) to compare transcriptomic profiles between sedentary and high PA groups in patients with AD. For mechanistic exploration, APP/PS1 transgenic mice underwent an 8-week treadmill-based aerobic exercise (AE) intervention (5 days/week, 40 min/day), followed by comprehensive assessments, including behavioral tests, pathological examinations, epigenetic and molecular biological analyses, and single-cell RNA sequencing.

RESULTS: Epidemiological analysis of the NHANES cohort revealed a nonlinear, dose-dependent relationship between PA and cognitive performance. MR supported a causal effect of genetically predicted higher PA on reduced AD risk. Transcriptomic profiling from GEO identified synaptic signaling and neurogenesis as key pathways modulated by exercise. In APP/PS1 mice, AE alleviated Aβ pathology and cognitive deficits, restored synaptic plasticity, and normalized synaptic protein expression. Mechanistically, AE activated ADRB2, triggering AMPKα phosphorylation and its interaction with the N-terminal (1-200 aa) region of p300. This interaction facilitated p300 nuclear translocation and subsequent enhanced histone H4K5 and H4K12 acetylation, promoting synaptic gene (e.g., GluN1) transcription. The AE-induced nuclear translocation of p300 and the improved synaptic plasticity in APP/PS1 mice were abolished by AMPKα inhibition with dorsomorphin (AMPK inhibitor, 10 mg/kg, intraperitoneal injection).

CONCLUSION: These findings unveil a previously unrecognized ADRB2-p-AMPKα-p300 axis that AE utilizes to orchestrate chromatin remodeling, counteracting synaptic degeneration and cognitive decline in AD, providing actionable targets for exercise-mimetic therapies.},
}

@article {pmid41669706,
year = {2024},
author = {Hoang, B and Pang, Y and Dodge, H and Zhou, J},
title = {Translingual Language Markers for Cognitive Assessment from Spontaneous Speech.},
journal = {Interspeech},
volume = {2024},
number = {},
pages = {977-981},
pmid = {41669706},
issn = {2958-1796},
abstract = {Mild Cognitive Impairment (MCI) is considered a prodromal stage of dementia, including Alzheimer's disease. It is characterized by behavioral changes and decreased cognitive function, while individuals can still maintain their independence. Early detection of MCI is critical, as it allows for timely intervention, enrichment of clinical trial cohorts, and the development of therapeutic approaches. Recently, language markers have been shown to be a promising approach to identifying MCI in a non-intrusive, affordable, and accessible fashion. In the InterSpeech 2024 TAUKADIAL Challenge, we study language markers from spontaneous speech in English and Chinese and use the bilingual language markers to identify MCI cases and predict the Mini-Mental Status Examination (MMSE) scores. Our proposed framework combines the power from 1) feature extraction of a comprehensive set of bilingual acoustic features, and semantic and syntactic features from language models; 2) careful treatment of model complexity for small sample size; 3) consideration of imbalanced demographic structure, potential outlier removal, and a multi-task treatment that uses the prediction of clinical classification as prior for MMSE prediction. The proposed approach delivers an average of 78.2% Balanced Accuracy in MCI detection and an averaged RMSE of 2.705 in predicting MMSE. Our empirical evaluation shows that translingual language markers can improve the detection of MCI from spontaneous speech. Our codes are provided in https://github.com/illidanlab/translingual-language-markers.},
}

@article {pmid41668152,
year = {2026},
author = {Xu, P and Zhang, H and Zhu, S and Kong, Y},
title = {ICE: robust detection of cellular senescence from weak single-cell signatures using imputation-based marker refinement.},
journal = {Genome biology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13059-026-03997-0},
pmid = {41668152},
issn = {1474-760X},
support = {2024FGC1004//the Interdisciplinary Research Program for Young Scholars from Southeast University/ ; 32570780//National Natural Science Foundation of China/ ; 32470666//National Natural Science Foundation of China/ ; },
abstract = {Detecting senescent cells from single-cell RNA-seq data remains challenging due to the weak and non-specific expression of canonical markers. Here, we demonstrate that simple expansion of these low-signal marker sets does not improve detection accuracy. To address this limitation, we develop ICE (Imputation-based Cell Enrichment), a computational framework that integrates expression imputation with marker refinement. ICE improves the detection of senescent cells in pancreatic β cells and microglia from Alzheimer's disease samples. This tool enables reliable identification of senescence-associated cell populations, facilitating more detailed analyses of their heterogeneity and temporal dynamics across human tissues and disease contexts.},
}

@article {pmid41668150,
year = {2026},
author = {Zilioli, A and Mohanty, R and Rosenberg, A and Matton, A and Granberg, T and Hagman, G and Spallazzi, M and Ferreira, D and Kivipelto, M and Westman, E},
title = {MRI-based atrophy subtypes in a young memory clinic cohort: associations with clinical and biomarker profiles.},
journal = {Alzheimer's research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13195-026-01972-2},
pmid = {41668150},
issn = {1758-9193},
}

@article {pmid41667812,
year = {2026},
author = {Heidt, A},
title = {Coffee linked to slower brain ageing in study of 130,000 people.},
journal = {Nature},
volume = {},
number = {},
pages = {},
pmid = {41667812},
issn = {1476-4687},
}

@article {pmid41667797,
year = {2026},
author = {Darvas, M and Cook, DG and Scimemi, A},
title = {Decoding Alzheimer's Disease One Cell Class at a Time.},
journal = {Cellular and molecular neurobiology},
volume = {},
number = {},
pages = {},
doi = {10.1007/s10571-026-01685-y},
pmid = {41667797},
issn = {1573-6830},
support = {R01AG075338/AG/NIA NIH HHS/United States ; IOS2011998//Division of Integrative Organismal Systems/ ; R56NS14042301/NS/NINDS NIH HHS/United States ; },
abstract = {Multimodal imaging-based on single-cell genomics and spatial transcriptomics has shed new light on the taxonomy of genetically defined cell clusters in the mammalian brain. While transcriptomic approaches have revolutionized our ability to classify brain cells, their true value emerges when they are interpreted in conjunction with anatomical, physiological, and translational frameworks. Accordingly, significant progress has been made to elucidate relationships between gene expression, electrical and morphological properties of some of these clusters. This rapidly growing body of work shows not only that the cell cluster composition varies across brain regions but also evolves over time and changes during the progression of disease states like Alzheimer's disease. Given this complexity, integrating transcriptomic, structural, and functional data is now becoming essential for drawing meaningful comparisons across studies. In this review, we summarize these findings and discuss how this knowledge base is shifting towards more integrative approaches, quickly challenging current ideas regarding the genetic, molecular, and cellular underpinnings of Alzheimer's disease.},
}

@article {pmid41667691,
year = {2026},
author = {Alanís-Bernal, M and Melgarejo, L and Boada-Oller, L and Rios, S and Maisterra, O and Ballvé, A and Buongiorno, M and Giraldo, D and Delgado, P and Gutiérrez, B and Liébana, D and Palasí, A},
title = {Characterization of neuropsychiatric symptoms in patients with early-stage Alzheimer's disease in a specialized outpatient clinic.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {47},
number = {3},
pages = {249},
pmid = {41667691},
issn = {1590-3478},
mesh = {Humans ; Female ; Male ; *Alzheimer Disease/psychology/complications/cerebrospinal fluid/diagnostic imaging/physiopathology ; Aged ; Retrospective Studies ; Aged, 80 and over ; Positron-Emission Tomography ; Ambulatory Care Facilities ; *Psychotic Disorders/etiology ; tau Proteins/cerebrospinal fluid ; },
abstract = {OBJECTIVE: To describe the frequency and temporal onset of neuropsychiatric symptoms (NPS) around the diagnosis of Alzheimer's disease (AD) and to explore their associations with clinical and paraclinical variables.

METHODS: We conducted a retrospective observational study of patients diagnosed with AD between 2020 and 2024, including NPS emerging from six years before to four years after diagnosis. Symptoms were classified by temporal onset as preNPS or postNPS and categorized into affective, psychotic, and behavioral domains. Clinical and demographic data, cerebrospinal fluid (CSF) biomarkers, and FDG-PET imaging findings were collected.

RESULTS: Among 184 patients (mean age 76.7 ± 9.0 years; 68% female), preNPS occurred in 78.2% and postNPS in 53.8%. Psychotic preNPS were associated with older age (81.4 ± 8.6 vs. 76.3 ± 8.9 years; p = 0.049), lower Mini-Mental State Examination scores (19.9 ± 3.7 vs. 22.1 ± 4.1; p = 0.033), and use of benzodiazepines (38.5% vs. 14.0%; p = 0.036) and antipsychotics (61.5% vs. 7.0%; p < 0.001). Affective preNPS were more common in women (71.9% vs. 55.4%; p = 0.029) and were associated with antidepressant use (p < 0.001) and lower alcohol intake (p = 0.018). Behavioral preNPS predominated in men (57.1% vs. 30.1%; p = 0.013) and were associated with a greater preservation of temporal lobe metabolism in FDG-PET imaging (28.0% vs. 76.2%; p = 0.04). PostNPS correlated with disease duration (r = 0.19; p = 0.01) and higher CSF total tau levels (386.9 ± 112.8 vs. 347.1 ± 148.9; p = 0.04).

CONCLUSION: NPS are frequent in early-stage AD, with psychotic preNPS linked to older age and greater cognitive decline, and postNPS correlating with disease duration and CSF tau, indicating an association with neurodegeneration.},
}

Humans
Female
Male
*Alzheimer Disease/psychology/complications/cerebrospinal fluid/diagnostic imaging/physiopathology
Aged
Retrospective Studies
Aged, 80 and over
Positron-Emission Tomography
Ambulatory Care Facilities
*Psychotic Disorders/etiology
tau Proteins/cerebrospinal fluid

@article {pmid41667529,
year = {2026},
author = {Hariharan, J and Jothi, R},
title = {Alzheimer's disease prediction using deep learning and XAI based interpretable feature selection from blood gene expression data.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-35260-8},
pmid = {41667529},
issn = {2045-2322},
abstract = {Alzheimer's disease (AD), a type of neurodegenerative disorder, has seen an increase in cases over the past decade, necessitating the construction of a comprehensive early detection method. Existing methods are typically invasive and costly, so our research concentrates on blood gene expression as a possible biomarker for early diagnosis of AD. Many research directions using machine learning and deep learning techniques exist in the literature for AD diagnosis. However, most of them use MRI scans as the primary data, and very few studies have been carried out on the use of blood gene biomarkers. The analysis of blood gene expression data is complicated by its high dimensionality and limited sample size. In this paper, we attempt to address these issues by applying multiple feature selection methods to identify the critical genes that act as biomarkers for AD diagnosis. To select the genes linked to AD and identify AD patients, we employ four feature selection approaches, including Chi-square, ANOVA, Recursive Feature Elimination (RFE), and ElasticNet, and build two deep learning models for AD classification. The selected genes are assessed with nested five-fold cross-validation to avoid overfitting. Further, we employ SHapley Additive exPlanations (SHAP), an Explainable AI (XAI) model, for ranking the selected genes and explaining why the feature selection algorithms predict a subset of genes as probable biomarkers. Generative Adversarial Network (GAN)-based data augmentation is used to address the issue of small sample size and improve model generalization. We demonstrate the results of feature selection and AD classification on three blood gene expression datasets, namely GSE63060, GSE63061, and ADNI, and their integrated version. Experimental results indicate that the deep neural network classifier achieved an accuracy of 91% and a precision of 95% in identifying AD samples. Feature selection along with data augmentation has significantly enhanced the precision and interpretability of early detection of AD using blood gene expression.},
}

@article {pmid41667435,
year = {2026},
author = {Blackburn, E and Birsa, N and Lopes, AT and Fisher, EMC and Lazo, OM and Schiavo, G},
title = {Impaired BDNF-TrkB trafficking and signalling in Down syndrome basal forebrain neurons.},
journal = {Cell death & disease},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41419-026-08464-z},
pmid = {41667435},
issn = {2041-4889},
support = {107116/Z/15/Z and 223022/Z/21/Z//Wellcome Trust (Wellcome)/ ; },
abstract = {Brain derived neurotrophic factor (BDNF) and its receptor tropomyosin-related kinase B (TrkB) play crucial roles in neuronal development, synaptic transmission, and neuroplasticity. Deficits in BDNF/TrkB signalling and trafficking have been identified in several neurodegenerative diseases, including Alzheimer's disease (AD). Individuals with Down syndrome (DS) are at an increased risk of developing AD compared to the general population. Basal forebrain neurons (BFNs) are among the first to degenerate in AD and DS, but the mechanisms underlying their vulnerability remain unclear. Using BFNs derived from the Dp1Tyb mouse model of DS, we investigated neurotrophic signalling and trafficking deficits in AD-DS. We found enlarged early endosomes and elevated levels of active Rab5, a GTPase critical for early endosome formation, in Dp1Tyb BFNs. These abnormalities were associated with impaired transport of internalised TrkB from axon terminals to the soma. Using microfluidic devices, we demonstrated that axonal BDNF stimulation enhanced signalling endosome dynamics in wild-type but not Dp1Tyb BFNs, which is likely due to impaired axonal ERK1/2 signalling. Our findings establish a link between Rab5 hyperactivation, endosomal dysfunction, and impaired ERK1/2 signalling, highlighting the interplay between trafficking and neurotrophic signalling, and underscore the importance of targeting endolysosomal and signalling pathways to mitigate neuronal dysfunction in AD-DS.},
}

@article {pmid41667430,
year = {2026},
author = {Rossini, PM and Pappalettera, C},
title = {Should all MCI with Alzheimer's biological diagnosis receive anti-amyloid therapy?.},
journal = {Cell death & disease},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41419-026-08456-z},
pmid = {41667430},
issn = {2041-4889},
abstract = {Our perspective addresses one of the most pressing and timely debates in contemporary neurology and health policy: whether the recent approval of anti-amyloid monoclonal antibodies for Alzheimer's disease should extend to all individuals with mild cognitive impairment (MCI; a large population of tens of millions of individuals worldwide mainly represented in Countries with aged population) who test positive for amyloid biomarkers, despite wide variability in prognosis and therapeutic response and the epidemiological demonstration that only about half of them manifest symptoms of dementia. The manuscript highlights three central themes. First, while epidemiological and meta-analytic data confirm that MCI significantly increases the risk of dementia, more than half of affected individuals-many of whom are biomarker-positive for amyloid/tau-do not progress to dementia even over long- term follow-up. Second, recently approved anti-amyloid therapies, although representing a landmark in disease-modifying treatments, carry high costs, non-negligible risks (particularly amyloid-related imaging abnormalities), and uncertain long-term real-world benefits. Third, indiscriminate prescription of these agents risks exposing large numbers of subjects to unnecessary harm while placing unsustainable burdens on healthcare systems. We argue that the field should urgently move to identify and validate accurate and sustainable instruments for risk-stratified treatment pathways, integrating genetic, clinical, neuropsychological, neuroimaging, and fluid biomarker data including risk and resilience factors to refine prognostication. In addition, we call on the scientific community, journals, and policymakers to foster dialog that bridges neurology, geriatrics, bioethics, health economics, and patient advocacy, so that clinical innovation is matched by ethical responsibility and equitable implementation.},
}

@article {pmid41667287,
year = {2026},
author = {Casper, A and Bolin, J},
title = {Alzheimer Disease and the Utility of PET.},
journal = {Journal of nuclear medicine technology},
volume = {},
number = {},
pages = {},
doi = {10.2967/jnmt.125.271758},
pmid = {41667287},
issn = {1535-5675},
abstract = {Alzheimer disease (AD) is the most common cause of dementia and one of the leading causes of death in adults age 65 y or older in the United States. AD presents with symptoms of cognitive impairment that worsen with disease progression, ultimately affecting an individual's functional abilities, independence, and overall health. Historically, treatment has relied on the mitigation of the adverse effects of the disease; however, the recent development of antiamyloid monoclonal antibodies allows for the targeting of pathologic factors that drive the progression of disease. Nuclear medicine has established itself as a useful tool in the evaluation of AD through the use of PET tracers, which target pathologic biomarkers such as amyloid-β and tau proteins, as well as metabolic processes reflective of neurodegenerative damage. Amyloid-β PET imaging and quantification have recently gained interest for their ability to more effectively diagnose AD and identify patients eligible for treatment with new antiamyloid therapies.},
}

@article {pmid41667284,
year = {2026},
author = {Doroudinia, A and York, B and Colletti, PM},
title = {Quantitative Amyloid Brain Imaging: A Literature Review of the Centiloid Scale in Alzheimer Disease Evaluation.},
journal = {Journal of nuclear medicine technology},
volume = {},
number = {},
pages = {},
doi = {10.2967/jnmt.125.271678},
pmid = {41667284},
issn = {1535-5675},
abstract = {Amyloid PET has become a pivotal imaging biomarker for Alzheimer disease (AD), enabling in vivo detection and quantification of β-amyloid deposition. However, variability in quantitative measurements across tracers, scanners, and analysis methods has considerably limited direct comparison of amyloid burden between studies and centers. To address this issue, the Centiloid Project has been developed to provide a standardized quantitative scale for amyloid PET, harmonizing results across tracers and institutions. In this literature review, we aim to summarize current evidence on the development, validation, and clinical application of the Centiloid scale in amyloid PET imaging, emphasizing its methodologic foundations, tracer-specific conversions, and diagnostic thresholds. Methods: A literature review was conducted using PubMed, Scopus, and Embase databases from January 2015 through October 2025. Search terms included "amyloid PET," "Centiloid," "SUVR," and "Alzheimer disease." We reviewed articles with quantitative amyloid PET analyses and Centiloid conversion and studies which compared multiple tracers using MIMneuro software Centiloid calibration. Results: The Centiloid method demonstrates strong intertracer and interscanner harmonization when standardized to the [11]C-Pittsburgh compound B reference, with high correlation (r [2] > 0.9) across [18]F-labeled tracers, including florbetapir, flutemetamol, and florbetaben. Most articles identified a Centiloid threshold between 20 and 25 Centiloids as indicative of significant amyloid pathology. Implementation of the Centiloid framework improved comparability across clinical trials and longitudinal studies, facilitating integration into the AT(N) research framework. Conclusion: The Centiloid scale represents a critical advancement in quantitative amyloid PET imaging, providing a universal reference that enhances data reproducibility, cross-trial comparisons, and clinical decision-making. Continued work is needed to expand standardization for novel tracers and hybrid imaging systems, ensuring full clinical translation of this metric in dementia imaging.},
}

@article {pmid41667283,
year = {2026},
author = {Johnson, SL},
title = {Brain Primer, Part 2: Pathophysiology of Neurodegeneration.},
journal = {Journal of nuclear medicine technology},
volume = {},
number = {},
pages = {},
doi = {10.2967/jnmt.125.271788},
pmid = {41667283},
issn = {1535-5675},
abstract = {Neurodegenerative diseases are characterized by progressive neuronal dysfunction, synaptic loss, and decline in cognitive, behavioral, or motor function. Understanding these disorders requires a foundational knowledge of neuroanatomy and physiology. Although normal aging leads to expected neuronal loss and changes in gray and white matter, neurodegenerative diseases are marked by systematic and progressive destruction of normal anatomy and function. Neurodegenerative diseases involve several key features, such as accumulation of amyloid-β plaques, tau hyperphosphorylation, microtubule destabilization, synaptic degeneration, and widespread neuroinflammatory responses driven by microglia and astrocytes. This article provides an integrated review of neurodegenerative mechanisms and provides a pathophysiologic overview of neurodegenerative diseases relevant to nuclear medicine and molecular imaging.},
}

@article {pmid41667282,
year = {2026},
author = {Grabher, BJ},
title = {Centiloids in Amyloid PET: A Practical Guide to Quantitation Interpretation.},
journal = {Journal of nuclear medicine technology},
volume = {},
number = {},
pages = {},
doi = {10.2967/jnmt.125.271823},
pmid = {41667282},
issn = {1535-5675},
abstract = {The approval of disease-modifying antiamyloid therapies has expanded the clinical role of amyloid PET beyond diagnostic confirmation to include baseline characterization and longitudinal monitoring of treatment response. Although visual interpretation remains the clinical standard for amyloid PET, it may be limited in borderline cases and when assessing subtle changes in amyloid burden over time. Quantitative amyloid PET provides objective measures that complement visual assessment, with z scores, SUV ratios, and Centiloid scaling offering increasing clinical utility. The Centiloid scale standardizes amyloid PET quantification across tracers, scanners, and institutions by anchoring measurements to biologically defined reference points, enabling consistent interpretation and comparison. This article describes the principles of amyloid PET quantification, explains the origin and interpretation of Centiloids, and discusses their role in therapy monitoring and clinical decision-making. Understanding quantitative amyloid PET and its limitations is essential for nuclear medicine professionals in the evolving landscape of Alzheimer disease imaging.},
}

@article {pmid41667280,
year = {2026},
author = {Skyles, T and Bouchal, SM and Giarratana, A and Wengler, J and Hart, I and Greig, E and Singh, H and Huang, SS and Martinez, F and Nguyen, B and Shin, CH and Yang, M and Parent, E and Robb, WH and Franceschi, AM and Burkett, B and Johnson, D and Koran, ME},
title = {PET Imaging in Alzheimer Disease in the Era of Antiamyloid Therapy in the United States: Clinical Utility, Quantification, and Policy Landscape.},
journal = {Journal of nuclear medicine technology},
volume = {},
number = {},
pages = {},
doi = {10.2967/jnmt.125.271835},
pmid = {41667280},
issn = {1535-5675},
abstract = {Alzheimer disease (AD) is increasingly diagnosed using molecular imaging biomarkers. PET imaging provides the opportunity to visualize amyloid and tau aggregates and in vivo neurodegenerative changes. These techniques provide exciting new avenues toward diagnosis, disease staging, and therapeutic monitoring of AD. Methods: This review details recent advances in amyloid PET, tau PET, and [18]F-FDG PET as they relate to the diagnosis, staging, and treatment of AD. The increasing roles of PET in the biologically based diagnosis of AD and antiamyloid immunotherapy response monitoring are addressed. Results: Amyloid PET enables improved detection of amyloid-β plaques within the brain. Amyloid PET is increasingly vital for confirming AD diagnoses given the emergence of antiamyloid immunotherapies, which require biomarker-verified amyloid positivity to initiate treatment. Tau PET provides a direct measure of neurofibrillary tangle pathology and is useful for disease staging, the interpretation of atypical clinical presentations, and treatment decision-making. [18]F-FDG PET plays a vital role in distinguishing AD from other dementia subtypes. Expanded reimbursement policies for amyloid and tau PET have increased accessibility to these modalities. Finally, quantitative methods facilitate interscan reproducibility and permit therapeutic monitoring. Conclusion: Molecular neuroimaging is poised to play a central role in the biologic definition, diagnosis, staging, and management of AD. Integrating amyloid, tau, and FDG PET with clinical assessments and fluid biomarkers provides earlier and more accurate diagnoses, opening the door to personalized treatment.},
}

@article {pmid41667028,
year = {2026},
author = {Fu, W and Ho, PC},
title = {Blood-Based Biomarkers for Alzheimer's Disease: Advances in Early Detection and Monitoring of Age-Related Neurodegeneration.},
journal = {Ageing research reviews},
volume = {},
number = {},
pages = {103058},
doi = {10.1016/j.arr.2026.103058},
pmid = {41667028},
issn = {1872-9649},
abstract = {Alzheimer's disease (AD) presents a critical global challenge, accounting for over 60% of the 57 million current dementia cases worldwide, with prevalence projected to exceed 100 million by 2050. Traditional diagnostic approaches, such as cerebrospinal fluid (CSF) analysis and neuroimaging are constrained by invasiveness, high costs, and limited accessibility, particularly problematic in aging population where early detection is crucial for effective intervention. This review synthesizes recent advances in blood-based biomarkers for AD, specifically phosphorylated tau proteins (p-tau217, p-tau181), neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and the amyloid-β42/40 ratio. These minimally invasive biomarkers demonstrate exceptional diagnostic accuracy with p-tau217 achieving AUC values greater 0.93 and 91% positive predictive value in detecting AD pathology, Critically, these biomarkers can identify pathological changes 15-20 years before symptom onset, with plasma p-tau217 levels increasing over 8.5% annually during preclinical stages. We propose that dried blood spots (DBS), containing both arterial and venous blood components, offer superior representation of brain-derived substances at their first systematic distribution after cardiac output. Ultrasensitive technologies like Simoa and mass spectrometry now enable femtomolar-level detection, revolutionizing of AD diagnostics. However, challenges persist in assay standardization persist in assay standardization, and population-specific validation. Overcoming these barriers to integrate blood biomarkers with DBS technology represents a transformative shift toward accessible, scalable screening in aging communities, offering a paradigm shift in preventing age-related neurodegeneration through early detection and timely intervention.},
}

@article {pmid41667027,
year = {2026},
author = {Valiantis, S and Perentos, N and Koupparis, AM and Hadjipapas, A and Papacostas, SS and Kousiappa, I},
title = {Fine Motor Function Deficits in the 5xFAD Mouse Model of Alzheimer's Disease.},
journal = {Behavioural brain research},
volume = {},
number = {},
pages = {116097},
doi = {10.1016/j.bbr.2026.116097},
pmid = {41667027},
issn = {1872-7549},
abstract = {Alzheimer's disease (AD) involves not only progressive memory and cognition deficits but also motor impairments, including disturbed balance and activity levels and gait dysfunction. We examined age-related changes in fine motor skills of an Alzheimer's mouse model, the transgenic 5xFAD, from 3 to 9 months of age (3M, 9M), using a battery of behavioral tests including the rotarod for motor coordination and balance, balance beam test for fine motor precision and coordination, and single-pellet reaching test for forelimb dexterity. Rotarod test showed that 9M 5xFAD mice displayed mild motor coordination deficits, spending less time on the rod and falling at lower speeds than 9M WT mice. In the balance beam test, 9M 5xFAD mice exhibited significantly slower traversal times compared to other groups and demonstrated frequent foot slips and dragging behavior with more pronounced effects on the narrower beam. The single-pellet reaching test revealed impaired fine limb movements in 9M 5xFAD mice, with reduced success rates and slower speed than the other groups. This study showed that 9M 5xFAD mice exhibited the most impaired performance at each assay in an age-dependent manner, suggesting that the accumulation of the underlying AD-related pathology affects motor function, extending even to fine motor skills.},
}

@article {pmid41666965,
year = {2026},
author = {Sun, L and Xu, X and Wang, Z and Meng, Y and Li, Y and Hou, Y and Gao, X and Cui, H and Li, Y},
title = {Effects of Different Dietary Restriction Regimens on Cognitive Function and Pathological Markers in Alzheimer's Disease Mouse Models：A Systematic Review and Meta-Analysis.},
journal = {Neuroscience and biobehavioral reviews},
volume = {},
number = {},
pages = {106601},
doi = {10.1016/j.neubiorev.2026.106601},
pmid = {41666965},
issn = {1873-7528},
abstract = {Dietary restriction (DR) has emerged as a promising non-pharmacological intervention for Alzheimer's disease (AD). This systematic review and meta-analysis provides the first comprehensive comparison of five dietary restriction regimens in Alzheimer's disease mouse models. Analysis of 23 studies demonstrates that caloric restriction yields the most consistent benefits. While intermittent fasting exhibits model-dependent efficacy-improving recognition memory but exacerbating neuroinflammation in 5×FAD models. The fasting-mimicking diet showed the largest effect size. From a geroscience perspective, these findings support a precision nutrition framework for Alzheimer's disease, suggesting that future interventions should be tailored to individual pathological profile, inflammatory status, and impaired cognitive subdomains to optimize therapeutic efficacy.},
}

@article {pmid41666775,
year = {2026},
author = {Chaudhari, S and Shinde, A and Salunke, M and Bairagi, S and Dhage, A and Patel, P and Rathod, V and Pathare, S and Altwaijry, N and Khan, MS},
title = {Investigating the anti-Alzheimer potential of biogenic compounds from Zinc15 database as NMDA antagonist: An in-silico approach.},
journal = {Journal of molecular graphics & modelling},
volume = {144},
number = {},
pages = {109277},
doi = {10.1016/j.jmgm.2026.109277},
pmid = {41666775},
issn = {1873-4243},
abstract = {Alzheimer's disease is an unavoidable neurological disorder in which the death of brain cells brings on memory loss, cognitive decline, and eventual dementia. There is no recognized treatment for Alzheimer's illness. By the year 2050, it is expected that the global population will witness approximately 100 million cases of Alzheimer's disease (AD). Despite recognizing AD as a formidable illness for over a century, no effective cure has been discovered thus far. Synaptic dysfunction could result from disturbed synaptic calcium handling caused by excessive activation of glutamate receptors, particularly the N-methyl-D-aspartate receptors (NMDARs). Glutamate serves as the brain's primary excitatory neurotransmitter, acting on ionotropic and metabotropic glutamate receptors. In recent years, several pharmacologically active substances derived from plants, animals, and microbes have shown promise in treating AD by focusing on various pathogenic processes. Initially, we used virtual screening to assess natural product-like compounds against NMDA receptors. In this research study, we have screened a natural compound database derived from zinc15. The best candidate was then validated through molecular dynamics simulation (MDS). The results revealed that out of 4221 compounds tested, only 165 showed superior binding interactions compared to native ligands, making them inhibitors for protein. Further analysis using ADMET indicates favorable drug-like properties, particularly for CNS drug-likeness. The MDS results, including RMSD, RMSF, Rg, and residue interactions, indicated a strong and stable association between top molecules and target protein. This confirms that top molecules can effectively remain within the binding pockets of the target proteins, forming stable protein-ligand complexes.},
}

@article {pmid41666658,
year = {2026},
author = {Grillenberger, AJ and Shenton, N and Lauritzen, M and Benedek, K and Puthusserypady, S},
title = {Exploring the potential of explainable deep learning for EEG-based cognitive decline prediction.},
journal = {Computers in biology and medicine},
volume = {204},
number = {},
pages = {111538},
doi = {10.1016/j.compbiomed.2026.111538},
pmid = {41666658},
issn = {1879-0534},
abstract = {OBJECTIVE: Detecting Alzheimer's disease (AD) at an early stage is essential for administering effective treatments and preventing neuronal damage. Unfortunately, current diagnostic techniques are often invasive and expensive. Our research focuses on creating a cost-effective and non-invasive method for the early detection of cognitive decline.

METHODS: Using a publicly available dataset of resting state electroencephalographic (EEG) data on healthy controls and patients with Mild Cognitive Impairment (MCI), two novel deep learning (DL) algorithms with self-attention mechanisms were developed and evaluated for their performance in predicting MCI and cognitive decline.

RESULTS: Both proposed DL algorithms outperformed a traditional convolutional neural network (CNN) model in predicting MCI, achieving test accuracy improvements of 8.5% and 10%, respectively, while utilizing significantly fewer trainable parameters. An ablation study highlighted the attention layer as a key feature, enhancing model accuracy by 8.5%. Analysis of the attention layers indicated that beta band frequencies (13-30 Hz) were essential for distinguishing MCI from control subjects, highlighting the role of high EEG frequencies in early cognitive deficits. Predicting pre-clinical cognitive decline in healthy subjects proved more challenging than predicting diagnosed MCI. However, using transfer-learning methods, we achieved a test accuracy of 56.08%.

CONCLUSION: Our models achieved state-of-the-art results in the MCI classification task, and demonstrated learning progress in predicting cognitive decline in the preclinical stage. As this is the first time DL models have been evaluated to classify healthy subjects based on cognitive scores, where brain changes are minimal and difficult to detect, this study opens new avenues for discovering biomarkers in early AD diagnosis and facilitating early interventions. Interpretation of the trained DL attention models provided valuable insights that aligned with the existing brain research, serving as a helpful tool for validating AI in healthcare applications.},
}

@article {pmid41666657,
year = {2026},
author = {More, SA and Sikkalgar, A and Chourasiya, N and Agrawal, YO and Goyal, SN and Nakhate, KT and Mohd Siddique, MU and Rathod, SS},
title = {Hentriacontane alleviates streptozotocin-induced Alzheimer's disease-like conditions in rats: In silico and in vivo investigations revealed the unifying principles.},
journal = {Computers in biology and medicine},
volume = {204},
number = {},
pages = {111513},
doi = {10.1016/j.compbiomed.2026.111513},
pmid = {41666657},
issn = {1879-0534},
abstract = {Intracerebroventricular (ICV) streptozotocin (STZ) deveops Alzheimer's disease (AD)-like conditions in rodents, which are characterized by insulin resistance, tau pathology, and neurodegeneration. Hentriacontane, a natural compound found in various sources, including beeswax, possesses anti-inflammatory and antioxidant properties. In the present investigation, we performed in silico molecular docking, molecular dynamics, MMGBSA, PCA, and FEL analysis of hentriacontane and rivastigmine with acetylcholinesterase (AchE). Further, we assessed the in vivo neuroprotective effects of hentriacontane in an ICV-STZ-induced AD-like condition in rats. STZ (3 mg/kg/ICV) was injected into male Sprague-Dawley rats. Cognitive functions were evaluated by Barnes-Maze (BM), novel object recognition test (NORT), and passive avoidance test (PAT). Hentriacontane (3 and 5 mg/kg) and rivastigmine (1 mg/kg) were given intraperitoneally for 14 days. Brain-derived neurotrophic factor (BDNF), AchE, oxidative stress parameters including GSH, MDA, SOD, and CAT, and proinflammatory cytokines including IL-6, TNF-α, IL-1β, and NF-ҡB were measured via ELISA. Further, we have also estimated the BACE1 and NO levels. Histopathological evaluation was conducted using hematoxylin and eosin staining. In silico molecular docking, dynamics, and post-dynamics data revealed promising binding affinities of hentriacontane for AchE. Further, hentriacontane attenuated ICV-STZ-induced cognitive deficit in BM, NORT, and PAT. Additionally, altered oxidative stress, proinflammatory, and cell signalling parameters were restored. Histopathology revealed that the hentriacontane-treated group showed significant restoration of the small pyramidal cells in the CA1 and CA2 regions of the brain. Hentriacontane demonstrated neuroprotective effects by modulation of AchE, leading to improved cognitive functions as evidenced by in silico and in vivo investigations.},
}

@article {pmid41666521,
year = {2026},
author = {Qin, Z and Wang, Z and Gao, C and Yong, X and Hua, Y and Zhou, Y and Xie, J},
title = {Ultrasound-mediated blood-brain barrier opening for targeted neurological drug delivery.},
journal = {Biomaterials advances},
volume = {183},
number = {},
pages = {214754},
doi = {10.1016/j.bioadv.2026.214754},
pmid = {41666521},
issn = {2772-9508},
abstract = {Neurological disorders represent a devastating global health crisis, and the blood-brain barrier (BBB) remains a major obstacle for their treatment. Conventional strategies for BBB opening, including direct intracranial injection, osmotic disruption, receptor-mediated transcytosis, and nanoparticle carriers, often suffers from surgical invasiveness, systemic toxicity, poor biodistribution, and off-target effects. Ultrasound-mediated drug delivery has emerged as a revolutionary non-invasive technology for transient and targeted BBB opening, enabling enhanced penetration of therapeutic agents into the central nervous system. This review comprehensively summarizes the mechanisms underlying ultrasound-based delivery with focus on current delivery platforms including microbubble (MB)-assisted, nanoparticle-based, and MB-nanoparticle composite strategies. Furthermore, we highlight recent advances in the application of focused ultrasound (FUS) combined with MBs for the treatment of Alzheimer's disease, Parkinson's disease, and glioma. Finally, we discuss emerging technologies such as sonodynamic therapy and ultrasound-controlled magnetic nanorobots, while also addressing current challenges in this field. This review underscores the transformative potential of ultrasound-mediated drug delivery as a versatile platform for precision neurology. It also prospects future directions for advancing multidisciplinary research and clinical translation.},
}

@article {pmid41666126,
year = {2026},
author = {Yue, J and Jones, B and Tran, KH and Deen, M and Holicek, V and Cheng, WH and Michalik, M and Power, S and Wellington, CL and Watson, NV and Vocadlo, DJ},
title = {Pharmacological inhibition of O-GlcNAcase reduces pS129-α-synuclein positive aggregates in the substantia nigra of mThy1-hSNCA mice.},
journal = {Journal of Parkinson's disease},
volume = {},
number = {},
pages = {1877718X251410291},
doi = {10.1177/1877718X251410291},
pmid = {41666126},
issn = {1877-718X},
abstract = {BackgroundThe aggregation and spread of α-synuclein within brain are associated with the loss of dopaminergic neurons and the formation of Lewy bodies as seen in Parkinson's disease. Blocking the initiation of α-synuclein aggregation, or the spread of such aggregates, may offer disease-modifying approaches to slow disease progression. Previous studies have demonstrated that modification of aggregation prone proteins, including α-synuclein, with O-linked β-N-acetylglucosamine (O-GlcNAc) reduces their aggregation. Small molecule inhibitors of the enzyme O-GlcNAcase (OGA), which removes O-GlcNAc from proteins, confers neuroprotective benefits in various preclinical disease models of Alzheimer's and Parkinson's diseases.ObjectiveThis study investigates the effects of long-term pharmacological enhancement of O-GlcNAcylation in a transgenic mouse model of Parkinson's disease overexpressing human α-synuclein.MethodsThiamet-G was orally administered to mThy1-hSNCA and wild-type (WT) mice for ten months. Behavioral assessments were conducted to examine changes in locomotion and cognition. Histological analyses were performed to analyze α-synuclein aggregates and dopaminergic neurons in brain sections. Immunoblot and ELISA analyses were performed to analyze O-GlcNAc and soluble α-synuclein using brain lysates, respectively.ResultsThiamet-G increased the level of O-GlcNAc in the brain of both mThy1-hSNCA and WT mice. The levels of total α-synuclein in the brain were unaltered. However, Thiamet-G strongly attenuated the deposition of pS129-immunoreactive α-synuclein aggregates within the substantia nigra, prior to observable neurodegeneration. Thiamet-G also protected against locomotor decline.ConclusionsThese results support OGA inhibition as a therapeutic approach to block the pathological formation of toxic α-synuclein as a disease-modifying treatment against Parkinson's disease.},
}

@article {pmid41666058,
year = {2026},
author = {Zhang, H and Wang, D and Yang, J and Zhao, Y and Liu, Y and Zhu, R and Wang, L and Song, R and Zhang, W},
title = {Unsupervised Disentanglement of Brain Heterogeneity for Identifying Subtypes of Alzheimer's Disease.},
journal = {IEEE transactions on bio-medical engineering},
volume = {PP},
number = {},
pages = {},
doi = {10.1109/TBME.2026.3663181},
pmid = {41666058},
issn = {1558-2531},
abstract = {Neuroanatomical heterogeneity in Alzheimer's disease (AD) hinders precision diagnosis and treatment, as distinct brain phenotypes may correspond to different disease subtypes. However, MRI-based subtype classifications are often confounded by co-occurring pathologies and non-AD factors, such as genetic predisposition and environmental influences, limiting their clinical interpretability. We propose 3D-DisAD, an unsupervised deep learning framework that disentangles AD-specific neuroanatomical variations from unrelated influences and clusters patients into subtypes with homogeneous brain phenotypes. The framework comprises two synergistic networks: (1) Contrastive Disentanglement Network, which separates AD-specific variations from those shared by AD patients and healthy controls; and (2) Transformation Generation Network, which refines these disease-specific variations by transforming healthy brain representations into realistic, pathology-consistent anatomies via diffusion-based generative modeling. Evaluated on four public datasets, 3D-DisAD reveals strong correlations between the disentangled AD-specific variations and diverse clinical and biological profiles, validating their relevance. Using these variations, we identify four AD subtypes with significant differences in biomarkers, cognitive trajectories, and genetic signatures, and uncover distinct longitudinal progression patterns that suggest potential windows for early intervention. By disentangling AD-specific variations, our method enables more precise patient stratification and personalized treatments, particularly in the early stage of AD. Code is available at: https://github.com/cnuzh/3D-DisAD.},
}

@article {pmid41666016,
year = {2026},
author = {Wu, B and Niu, Z and Sui, Y},
title = {LAPTM proteins in neurological disorders - Autophagy-lysosome dysfunction and therapeutic targets: A review.},
journal = {Biomolecules & biomedicine},
volume = {},
number = {},
pages = {},
doi = {10.17305/bb.2026.13624},
pmid = {41666016},
issn = {2831-090X},
abstract = {Lysosomal-associated protein transmembrane (LAPTM) family members-LAPTM4A, LAPTM4B, and LAPTM5-regulate lysosomal integrity, autophagy-lysosome flux, lipid homeostasis, and immune signaling, pathways increasingly implicated in neurological disease. This review synthesizes structure-function evidence for LAPTM proteins and examines how their dysregulation contributes to Alzheimer's and Parkinson's disease, ischemia-reperfusion injury, and gliomas. Based on a targeted narrative analysis of primary and translational studies, we highlight that LAPTM proteins influence lysosomal acidification and membrane stability, endolysosomal trafficking, and ceramide/ion handling, thereby shaping protein aggregate clearance, oxidative stress responses, and microglia/macrophage polarization. Preclinical data link LAPTM5 to stroke outcomes via stress-kinase and lysosomal pathways, while LAPTM4A and LAPTM4B associate with glioma progression, immune evasion, and therapy resistance. Overall, LAPTM proteins represent promising biomarkers and therapeutic targets, warranting cell-type-resolved validation and central nervous system (CNS)-optimized delivery strategies, including gene therapy, small-molecule/degrader approaches, and multi-omics-guided patient stratification.},
}

@article {pmid41665901,
year = {2026},
author = {Halbgebauer, R and Gonzalez-Ortiz, F and Mayer, B and Berger, C and Bergmann, C and Rinderknecht, H and Barth, E and Wohlgemuth, L and Mannes, M and Otto, M and Tumani, H and Relja, B and Gebhard, F and Huber-Lang, M and Zetterberg, H and Halbgebauer, S and Blennow, K},
title = {Blood-Based Analysis of Different Tau Variants in Patients With Multiple Traumatic Injuries.},
journal = {JAMA network open},
volume = {9},
number = {2},
pages = {e2558573},
doi = {10.1001/jamanetworkopen.2025.58573},
pmid = {41665901},
issn = {2574-3805},
mesh = {Humans ; *tau Proteins/blood ; Male ; Female ; Adult ; Middle Aged ; Biomarkers/blood ; *Brain Injuries, Traumatic/blood ; Phosphorylation ; Cohort Studies ; Case-Control Studies ; },
abstract = {IMPORTANCE: With blood-based phosphorylated tau biomarkers soon to be used for diagnosis of Alzheimer disease, analyzing tau levels in other conditions could enhance biomarker interpretability. Moreover, mechanisms of tau release into circulation remain unclear.

OBJECTIVE: To evaluate concentrations of phosphorylated and nonphosphorylated tau variants in the blood of patients with multiple traumatic injuries on days 0, 1, 5, and 10 and investigate biological processes driving tau release.

This multiple-trauma cohort (injury severity score, ≥18) included 45 severely injured patients with (n = 27) and without (n = 18) moderate-to-severe traumatic brain injury on emergency computed tomographic imaging. Controls consisted of 24 healthy volunteers. Participants were recruited from December 1, 2013, to October 31, 2022. Blood samples were analyzed for brain-derived tau (BD-tau), total tau (t-tau), and phosphorylated tau 217 (p-tau217) and 231 (p-tau231) levels. Associations among tau concentrations, clinical data, and outcome (eg, Glasgow Coma Scale [GCS] score) were assessed. Data were analyzed from March 1, 2023, to September 30, 2024.

EXPOSURES: Serum BD-tau, t-tau, p-tau217, and p-tau231 levels.

RESULTS: A total of 214 serum samples were analyzed. Median age of the 45 patients was 48 (IQR, 33-60) years (35 [77.8%] male); median age of the 24 controls, 43 (IQR, 28-50) years (16 [66.7%] male). Median serum levels of tau variants were increased in patients with multiple traumatic injuries at day 0 compared with controls (t-tau: 43 [IQR, 21-95] vs 3 [IQR, 3-5] pg/mL; BD-tau: 78 [IQR, 30-343] vs 2 [IQR, 2-3] pg/mL; p-tau231: 61 [IQR, 21-79] vs 2 [IQR, 1-3] pg/mL; all, P < .001). Only median BD-tau levels remained elevated until day 10 (day 1, 25 [IQR, 14-69] pg/mL; day 5, 9 [IQR, 4-15] pg/mL; day 10, 8 [IQR, 4-18] pg/mL). Median tau levels at admission were higher in patients with lower GCS scores (BD-tau: 107 [ IQR, 59-838] vs 33 [IQR, 24-78] pg/mL [P = .01]; p-tau231: 76 [IQR, 36-114] vs 28 [IQR, 9-63] pg/mL [P = .02]). Elevated median tau levels were also observed in patients with hemorrhagic shock vs those without shock (eg, BD-tau on day 0: 113 [IQR, 78-378] vs 31 [IQR, 24-61] pg/mL; P = .002) and in nonsurvivors vs survivors with uncomplicated courses (eg, BD-tau on day 1: 92 [IQR, 22-527] vs 16 [IQR, 7-23] pg/mL; P = .009).

CONCLUSIONS AND RELEVANCE: In this exploratory study among a cohort of patients with multiple traumatic injuries, levels of tau variants reflected both direct and indirect neurological injury, with BD-tau showing the most persistent elevation in the acute phase.},
}

Humans
*tau Proteins/blood
Male
Female
Adult
Middle Aged
Biomarkers/blood
*Brain Injuries, Traumatic/blood
Phosphorylation
Cohort Studies
Case-Control Studies

@article {pmid41665822,
year = {2026},
author = {Matías-Guiu, JA and Ortega-Madueño, I and Gil-Moreno, MJ and Cárdenas, MC and Abizanda-Saro, P and Alcalá Ramírez Del Puerto, JM and López-Carbonero, JI and Valiente-Gordillo, E and Aguilera, L and Carrillo-Molina, T and García-Rama, M and Matarranz-González, S and Palacios-Sarmiento, M and Matías-Guiu, J and Gómez-Pinedo, U},
title = {Impact of blood p-tau217 testing on diagnosis and diagnostic confidence in cognitive disorders: a real-world clinical study.},
journal = {Journal of neurology},
volume = {273},
number = {2},
pages = {130},
pmid = {41665822},
issn = {1432-1459},
support = {INT20/00079//Instituto de Salud Carlos III/ ; INT23/00017//Instituto de Salud Carlos III/ ; CM23/00094//Instituto de Salud Carlos III/ ; Fondo Estrategia Enfermedades Neurodegenerativas//Ministerio de Sanidad, Consumo y Bienestar Social/ ; },
mesh = {Humans ; Male ; Female ; Aged ; *tau Proteins/blood ; Biomarkers/blood ; *Cognitive Dysfunction/diagnosis/blood ; Aged, 80 and over ; Middle Aged ; Alzheimer Disease/diagnosis/blood ; *Cognition Disorders/diagnosis/blood ; Neuropsychological Tests ; *Dementia/diagnosis/blood ; },
abstract = {BACKGROUND: The blood biomarker p-tau217 has demonstrated high accuracy in predicting underlying Alzheimer's disease (AD) pathology. However, its feasibility and impact on clinician confidence and diagnosis in real-world clinical settings remain underexplored. We aimed to evaluate the effect of implementing blood p-tau217 testing on both diagnosis and diagnostic confidence in patients with cognitive symptoms across two different clinical settings: general neurology consultations referred from primary care and a specialized memory unit.

METHODS: We included 200 consecutive new patients (38.5% with subjective cognitive complaints, 47.5% mild cognitive impairment, and 14% with dementia) evaluated for cognitive symptoms in two distinct clinical settings: general neurology and a memory unit. Attending neurologists were asked to record a pre-biomarker clinical diagnosis and their diagnostic confidence on a scale from 0 to 10. They repeated this assessment after receiving the p-tau217 results.

RESULTS: Across the whole sample, 51/200 patients (25.5%) had a change in their diagnostic category after receiving p-tau217 levels. Furthermore, diagnostic confidence significantly improved from 6.90 ± 1.74 at the first visit to 8.49 ± 1.68 after the test. Changes in diagnosis and confidence were observed in both general neurology and memory unit settings, and across all clinical stages (subjective cognitive complaints, mild cognitive impairment, and dementia). Compared with the final diagnosis, the pre-biomarker diagnosis was maintained in 71/200 cases (75.5%) (Kappa = 0.576), while the post-biomarker diagnosis was maintained in 189/200 cases (94.5%) (Kappa = 0.906).

CONCLUSIONS: Implementing p-tau217 in real-world clinical practice has a strong clinical impact, substantially improving diagnostic accuracy and confidence in both general neurology and memory units across all stages of cognitive decline.},
}

Humans
Male
Female
Aged
*tau Proteins/blood
Biomarkers/blood
*Cognitive Dysfunction/diagnosis/blood
Aged, 80 and over
Middle Aged
Alzheimer Disease/diagnosis/blood
*Cognition Disorders/diagnosis/blood
Neuropsychological Tests
*Dementia/diagnosis/blood

@article {pmid41665770,
year = {2026},
author = {Arora, A and Behl, T and Sehgal, A and Singh, S and Sharma, N and Abdellatif, AAH and Dailah, HG and Bhatia, S and Al-Harrasi, A and Aleya, L and Bungau, S},
title = {Retraction Note: Elucidating the promising role of traditional Chinese medicine in neuroprotection against oxidative stress encompassing Alzheimer's disease.},
journal = {Environmental science and pollution research international},
volume = {},
number = {},
pages = {},
doi = {10.1007/s11356-026-37499-0},
pmid = {41665770},
issn = {1614-7499},
}

@article {pmid41665751,
year = {2026},
author = {Voronova, AD and Karsuntseva, EK and Shishkina, VS and Chadin, AV and Fursa, GA and Gurin, PI and Kuznetsova, TV and Reshetov, IV and Shport, SV and Stepanova, OV and Chekhonin, VP},
title = {Clinical Trials of Cell Products for the Treatment of Alzheimer's Disease (Review).},
journal = {Bulletin of experimental biology and medicine},
volume = {},
number = {},
pages = {},
pmid = {41665751},
issn = {1573-8221},
abstract = {Existing approaches to the treatment of Alzheimer's disease are ineffective because they do not stop neurodegenerative processes in the brain and do not promote the regeneration of the nervous tissue. Cell therapy is a promising strategy for the treatment of this disease. This review discusses clinical studies of cell-based therapies for Alzheimer's disease, evaluates their therapeutic potential, and proposes strategies for developing safe, accessible, and effective cell products.},
}

@article {pmid41665706,
year = {2026},
author = {Giacomini, PS and Voss, P and Devonshire, V and Schneider, R and Macaron, G and Hussein, S and Blanchette, F and de Villers-Sidani, É},
title = {Eye tracking as a digital biomarker in neurodegenerative diseases.},
journal = {Journal of neurology},
volume = {273},
number = {2},
pages = {133},
pmid = {41665706},
issn = {1432-1459},
mesh = {Humans ; *Neurodegenerative Diseases/diagnosis/physiopathology/complications ; Biomarkers ; *Eye-Tracking Technology ; *Eye Movements/physiology ; },
abstract = {Oculomotor abnormalities are a common finding in neurodegenerative diseases due to degeneration of neural pathways and brain regions involved in controlling eye movements. Pathological changes to the dorsolateral prefrontal cortex, basal ganglia, superior colliculus and cerebellum produce subtle changes in eye-movement metrics that may not be detected by clinical examination. The present review addresses the potential use of eye-movement biomarkers in neurodegenerative conditions such as multiple sclerosis, Parkinson's disease, Alzheimer's disease and other dementias, and amyotrophic lateral sclerosis. Eye-movement metrics such as saccades, anti-saccades, fixation and smooth pursuit are prognostic of disease progression, can differentiate pathologic subtypes as an aid to diagnosis, and enable clinicians to evaluate early worsening of motor and cognitive function. The cost of medical technologies limits their optimal use and accessibility in clinical practice. The shortage of subspecialist neurologists further limits access to care. New eye-tracking technologies incorporated into widely-accessible digital devices such as smart phones and tablets now permit detailed assessments with minimal equipment requirements, providing an important non-invasive and potentially cost-effective method for patient evaluation in routine clinical practice and as an aid to treatment decision-making. Digital biomarkers can be readily employed by healthcare professionals such as family physicians, nurses and pharmacists to bridge the care gaps, potentially providing them with powerful tools that can be broadly adopted to improve the delivery of care to patients with neurodegenerative conditions.},
}

Humans
*Neurodegenerative Diseases/diagnosis/physiopathology/complications
Biomarkers
*Eye-Tracking Technology
*Eye Movements/physiology

@article {pmid41665145,
year = {2026},
author = {Baral, R and van Deventer, R and Lyubchenko, YL},
title = {Amyloid β-Cholesterol Interplay: Removal of Cholesterol From the Membranes to Catalyze Aggregation and Amyloid Pathology.},
journal = {Journal of neurochemistry},
volume = {170},
number = {2},
pages = {e70380},
doi = {10.1111/jnc.70380},
pmid = {41665145},
issn = {1471-4159},
support = {GM100156/NH/NIH HHS/United States ; },
mesh = {*Cholesterol/metabolism ; *Amyloid beta-Peptides/metabolism ; Humans ; *Peptide Fragments/metabolism ; *Cell Membrane/metabolism ; *Protein Aggregation, Pathological/metabolism/pathology ; Microscopy, Atomic Force ; Alzheimer Disease/metabolism/pathology ; Animals ; },
abstract = {The interplay between the cholesterol metabolism and assembly of Aβ42 (the 42-residue form of the amyloid-β peptide) peptides in pathological aggregates is considered one of the major molecular mechanisms in the development of Alzheimer's disease (AD). Numerous in vitro studies led to the finding that high cholesterol levels in membranes accelerate the production of Aβ aggregates. The molecular mechanisms explaining how cholesterol localized inside the membrane bilayer catalyzes the assembly of Aβ aggregates above the membrane remain unknown. We addressed this problem by combining different AFM modalities, including imaging and force spectroscopy, with fluorescence spectroscopy. Our combined studies revealed that Aβ42 was capable of removing cholesterol from the membrane. Importantly, physiologically low concentrations of Aβ42 demonstrate such ability. Extracted cholesterol interacts with Aβ42 and accelerates its on-membrane aggregation, which is a molecular mechanism explaining how cholesterol embedded in the membrane accelerates Aβ42 aggregation. The discovered ability of Aβ42 to remove cholesterol from membranes resulted in three major AD-related events. First, free cholesterol catalyzes the assembly of Aβ42 in aggregates, which is the mechanism by which physiologically important Aβ42 monomers are converted into their pathological form. Second, the release of cholesterol from membranes leads to its accumulation in the brain, which is one of the risk factors associated with disease development and progression. Third, cholesterol depletion decreases membrane stiffness, which can result in deterioration of the function of membrane-bound proteins, such as dendritic spine degeneration and, ultimately, synapse loss, a common pathological feature of AD.},
}

*Cholesterol/metabolism
*Amyloid beta-Peptides/metabolism
Humans
*Peptide Fragments/metabolism
*Cell Membrane/metabolism
*Protein Aggregation, Pathological/metabolism/pathology
Microscopy, Atomic Force
Alzheimer Disease/metabolism/pathology
Animals

@article {pmid41665021,
year = {2026},
author = {Elia, A and Parodi-Rullan, R and Vazquez-Torres, R and Carey, A and Zhao, H and Javadov, S and Fossati, S},
title = {Amyloid β Instigates Cardiac Neurotrophic Signaling Impairment, Driving Alzheimer's Associated Heart Disease.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e11924},
doi = {10.1002/advs.202511924},
pmid = {41665021},
issn = {2198-3844},
support = {PACure;CollaborativeResearchonAlzheimer'sDisease//Pennsylvania Department of Health/ ; 24POST1240115//American Heart Association/ ; AARG-20-685663/ALZ/Alzheimer's Association/United States ; R01NS104127//NIH National Institute of Neurological Disorders and Stroke/ ; R01AG062572//NIH National Institute on Aging/ ; SC1GM128210//National Institute of General Medical Sciences (NIGMS)/ ; },
abstract = {While a link between cardiovascular risk factors and increased Alzheimer's disease (AD) risk has been reported, it remains unclear whether AD pathology has a direct effect on cardiac function and myocardial innervation. AD and amyloidosis are known to impair neuronal function and affect brain neurotrophic factors (NGF and BDNF) expression. Amyloid aggregates and neuro-signaling impairments may also expose AD patients to peripheral nervous system deficits, promoting cardiac disorders. Here, we provide novel understanding of cardiac physiological impairment, amyloid pathology, neurotrophic factors loss, and impoverishment of cardiac neuronal fibers in Tg2576-AD mice hearts, human cardiomyocytes in culture, and human AD post-mortem left ventricular (LV) heart tissue. We reveal that Tg2576 animals exhibit increased myocardial fibrosis, amyloid β (Aβ) deposition, and brain/heart-axis neurotrophic deficiencies, resulting in myocardial denervation and cardiac dysfunction. Aβ oligomers challenge reduces BDNF expression in both human immortalized and iPSC-derived cardiomyocytes, by disrupting TrkB/CREB signaling. Analysis of human LV AD post-mortem tissue confirms cell and animal results. Our findings reveal potential pathways by which Aβ pathology may disrupt cardiac neurotrophic signaling and physiology, identifying a possible link between AD and heart degeneration.},
}

@article {pmid41664763,
year = {2026},
author = {Wang, AS and Marino, M and Helson, A and Abbasi, MH and Dally, J and Miulli, DE},
title = {Neuromodulation With Electromagnetic Field Stimulation via Gamma Oscillations Improved Mini-Mental State Examination Scores in Patients With Cognitive Impairment.},
journal = {Cureus},
volume = {18},
number = {1},
pages = {e101122},
pmid = {41664763},
issn = {2168-8184},
abstract = {BACKGROUND: Abnormalities in gamma oscillations have been found in neurological disorders that involve dementia, such as Alzheimer's disease. Neuromodulation via gamma stimulation has shown promising potential to enhance cognitive function in patients with Alzheimer's disease.

OBJECTIVE: In this pilot clinical trial, we describe recording and neuromodulation of brain electromagnetic field (EMF) at gamma oscillations, specifically 70 Hertz (Hz) to 100 Hz, and its effect on brain EMF waves, cognition, and memory as assessed with EMF recordings and Mini-Mental State Examination (MMSE) in patients with cognitive impairment. We hypothesize that EMF stimulation at 70-100 Hz will lead to a statistically significant improvement in MMSE compared with baseline. Additionally, we aim to refine EMF recording and stimulation protocols.  Methods: MMSE was performed before and after EMF recordings. We used a previously developed portable helmet system equipped with Mu-metal (MuMETAL, Magnetic Shield Corporation, Bensenville, IL) and copper shielding, embedded sensors, and EMF generators to record baseline brain EMF of patients with cognitive impairment, identify the sensor of interest and frequency of interest, deliver EMF stimulation at the frequency of interest at 10 Volts over 10 minutes, and record post-stimulation EMF.

RESULTS: Sixteen patients with cognitive impairment were included in this study. EMF recordings from six patients were used to refine analysis protocols, while ten new patients underwent stimulation. The mean pre-stimulation MMSE score was 13.8/30 points, and the mean post-stimulation MMSE score was 17.5/30 points (p=0.170).

CONCLUSIONS: In this pilot study, neuromodulation via EMF stimulation led to improvement in EMF waves and showed a trend toward cognitive and memory improvement without statistical significance in patients with cognitive impairment.},
}

@article {pmid41664707,
year = {2026},
author = {Xiang, Q and Shi, RL and Huang, YX and Liu, LN and Tao, JS and Li, XH and Li, XD},
title = {Oligodendrocyte: Development, Plasticity, Biological Functions, Diseases, and Therapeutic Targets.},
journal = {MedComm},
volume = {7},
number = {2},
pages = {e70618},
pmid = {41664707},
issn = {2688-2663},
abstract = {In the past few years, the incidence rate of central nervous system (CNS) diseases is still growing. Meanwhile, the molecular mechanism on the pathogenesis of neurological diseases remains elusive. Oligodendrocyte progenitor cells (OPCs) are distributed in the whole CNS and represent a population of migrating and proliferating adult progenitor oligodendrocytes that can be differentiated into oligodendrocytes (OLs). The main function of OLs is to produce myelin, the membrane wrapping tightly around the axon, which are associated with the myelination and remyelination. During regeneration, the new OLs from OPCs can regenerate lost myelin, which prevents axonal degeneration and restores its plasticity and function. Considering these energy-consuming processes, the high metabolic turnover OLs are susceptible to neurotoxic factors and its excitatory toxicity. Thus, the pathogenesis of OPC and OL are proven in neurological diseases, such as multiple sclerosis, Alzheimer's disease, major psychiatric diseases, and epilepsy. The current study reviewed the development, plasticity as well as application of OPCs and OLs researches on CNS diseases. Additionally, the effective methods and bioengineering technologies as well as biomaterials relevant to regenerative medicine are also discussed, which could provide the novel insight into the therapeutic treatment of those diseases, exploring new pathological clues, identifying the key molecules and targets as well as the potential biomarkers.},
}

@article {pmid41664541,
year = {2026},
author = {Cánovas, R and Fowler, CJ and Feizpour, A and Dóre, V and Bourgeat, P and Saad, ZS and Triana-Baltzer, G and Kolb, HC and Vandijck, M and Kollmorgen, G and Quijano-Rubio, C and Fripp, J and Laws, S and Bannon, AW and Blennow, K and Zetterberg, H and Rainey-Smith, S and Mathotaarachchi, S and Rowe, CC and Masters, CL and Doecke, JD and , },
title = {Plasma biomarker progression across the Alzheimer's disease amyloid beta and tau positron emission tomography trajectories.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {2},
pages = {e71145},
doi = {10.1002/alz.71145},
pmid = {41664541},
issn = {1552-5279},
support = {//AbbVie/ ; 2023-00356//Swedish Research Council/ ; 2022-01018//Swedish Research Council/ ; 2019-02397//Swedish Research Council/ ; 101053962//European Union's Horizon Europe research and innovation programme/ ; ALFGBG-71320//Swedish State Support for Clinical Research/ ; ADSF-21-831376-C//AD Strategic Fund/ ; ADSF-21-831381-C//AD Strategic Fund/ ; ADSF-21-831377-C//AD Strategic Fund/ ; ADSF-24-1284328-C//AD Strategic Fund/ ; 22HLT07//NEuroBioStand/ ; //Familjen Beiglers Stiftelse/ ; //Stiftelsen för Gamla Tjänarinnor/ ; FO2022-0270//Hjärnfonden/ ; //European Union's Horizon/ ; JPND2021-00694//European Union Joint Programme - Neurodegenerative Disease Research/ ; //National Institute for Health/ ; UKDRI-1003//UK Dementia Research Institute/ ; //Enigma Australia/ ; //Biogen/ ; //Eisai/ ; //Roche/ ; //Johnson and Johnson/ ; },
mesh = {Humans ; *tau Proteins/blood ; Positron-Emission Tomography ; *Amyloid beta-Peptides/blood ; *Alzheimer Disease/diagnostic imaging/blood ; *Biomarkers/blood ; Male ; Female ; Aged ; Disease Progression ; Brain/diagnostic imaging/metabolism ; Aged, 80 and over ; Phosphorylation ; },
abstract = {INTRODUCTION: With increased uptake in disease-modifying treatments for amyloid beta (Aβ) removal, it is important to measure performance of highly sensitive plasma biomarkers to detect the presence of Aβ and tau in cognitively impaired populations.

METHODS: In this study, we investigated a large set of plasma biomarkers for their capability to predict Aβ and tau positron emission tomography (PET) and their association with increasing Aβ and tau burden.

RESULTS: From the biomarkers assessed, tau phosphorylated at threonine 217 (pTau217) showed the largest increases across the full range of Aβ and tau levels. Furthermore, pTau217/Aβ42 had the smallest proportion of participants in the intermediate zone (∼4%) to predict Aβ status using a 90/90% dual cut-off for sensitivity and specificity, with < 20% of participants in the intermediate zone using the 95/95% dual cut-off.

DISCUSSION: While the studied biomarkers proved their utility to predict Aβ and tau PET at their respective thresholds, each has separate quantified responses to Aβ and tau aggregation.},
}

Humans
*tau Proteins/blood
Positron-Emission Tomography
*Amyloid beta-Peptides/blood
*Alzheimer Disease/diagnostic imaging/blood
*Biomarkers/blood
Male
Female
Aged
Disease Progression
Brain/diagnostic imaging/metabolism
Aged, 80 and over
Phosphorylation

@article {pmid41664517,
year = {2026},
author = {Silva Fernandes, A and Barbosa de Souza, Á and Benvindo de Souza, M and Madureira Almeida, L and Luiz Franco, O and Luiz Cardoso Bailão, EF and Borges, LL and Sérgio Nakao de Aguiar, A},
title = {DNA damage induced by fungicides triadimefon, triadimenol, and their mixture in human lymphocytes: cytogenotoxicity and computational analysis of metabolic pathways.},
journal = {Drug and chemical toxicology},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/01480545.2026.2626753},
pmid = {41664517},
issn = {1525-6014},
abstract = {Triadimefon (TF) and triadimenol (TN) are triazole fungicides widely used to prevent fungal infections in cereals, fruits, and other economically important crops. Their harmful effects on non-target organisms have been reported. This study investigated the cytogenotoxic effects of TF and TN, isolated and combined, at environmentally relevant concentrations (TF: 0.006, 0.012, and 0.024 mg/mL; TN: 1.5, 3.0, and 6.0 mg/mL; and 0.012 mg/mL TF + 3.0 mg/mL TN) on human lymphocytes using the trypan blue exclusion test and the comet assay. Additionally, in silico tools, BioTransformer and DIGEP-Pred, were employed to elucidate metabolic pathways more effectively for detoxifying these xenobiotics and to evaluate their putative effects on gene transcription, respectively. Exposure to TF and TN, either alone or in combination, did not affect lymphocyte viability at the tested concentrations. However, both compounds induced an increase in the percentage of DNA strand breaks after treatment. The in silico predictions suggested that the interaction with the cytochrome P450 isoforms (CYP1A2, CYP2A6, CYP2C9, and CYP2D6) differed for each compound analyzed. Gene expression prediction indicated that TF and TN may up-regulate genes involved with hormonal alterations, Alzheimer's disease risk, and cancer progression (SF1, SPON1, ADGRF5, and RORB). While they may down-regulate a gene involved with changes in heart rhythm and neurotoxicity (HCN1). In conclusion, our findings reinforced that the triazole fungicides TF and TN, while effective in agriculture, may pose risks to genomic stability in humans, highlighting the importance of biomonitoring studies in exposed populations.},
}

@article {pmid41664510,
year = {2026},
author = {Bouwman, MMA and Frigerio, I and Graaf, YG and van de Berg, WDJ and Jonkman, LE},
title = {Distinct regional patterns of synaptic vulnerability across hippocampal and parahippocampal subregions in Alzheimer's disease.},
journal = {Brain pathology (Zurich, Switzerland)},
volume = {},
number = {},
pages = {e70081},
doi = {10.1111/bpa.70081},
pmid = {41664510},
issn = {1750-3639},
support = {WE.03-2020-02//Alzheimer Nederland/ ; S-000438//LSH-TKI PPP/ ; },
abstract = {Synaptic loss in the (para)hippocampus is a major contributor to cognitive decline in Alzheimer's disease (AD), yet its regional specificity and pathological correlates remain poorly understood. Here, we quantified synaptophysin-positive puncta across hippocampal subregions (CA4, CA2, CA1, and subiculum) and parahippocampal cortex (entorhinal cortex, parahippocampal and fusiform gyrus) in postmortem tissue from 28 AD and 17 controls, and assessed relationships to neuropathological severity and cognitive decline. Amyloid-β, phosphorylated tau (p-tau) load and neurofilament light (NfL) immunoreactivity were quantified, and Clinical Dementia Rating scores were collected as a cognitive measure. Group differences were analyzed with linear mixed models; correlations between synaptic puncta, pathology and cognitive scores with linear regressions, corrected for age, sex and multiple comparisons. We found selective synaptic loss in the entorhinal cortex (-14%, p = 0.017) and parahippocampal gyrus (-14%, p = 0.021) in AD versus controls. Hippocampal synaptic density negatively correlated with amyloid-β in controls (r = -0.52, p < 0.001) and positively in AD (r = 0.25, p = 0.007), suggesting a disease-dependent shift. In AD, hippocampal, but not parahippocampal, subregions with higher p-tau burden showed greater synaptic density (r = 0.21, p = 0.003), raising questions about the role of p-tau in synaptic loss at late stages. Axonal damage (i.e., higher NfL load) in the parahippocampal cortex associated with synaptic loss locally and in interconnected subregions. Worse cognitive performance was strongly associated with synaptic loss in the CA1 (r = -0.64, p = 0.003), subiculum (r = -0.62, p = 0.012), entorhinal cortex (r = -0.60, p = 0.008), parahippocampal (r = -0.48, p = 0.041) and fusiform gyrus (r = -0.67, p = 0.002). These findings highlight the vulnerability of the entorhinal cortex and parahippocampal gyrus to synaptic loss in AD. Our results suggest that amyloid-β and p-tau pathology may play a limited role in synaptic loss at end-stage disease, and the strong link between synaptic loss in (para)hippocampal subregions and cognitive decline underscores the need for monitoring synaptic change in light of disease progression and evaluating therapeutic interventions.},
}

@article {pmid41664462,
year = {2026},
author = {Zawadzki, S and Suty, S and Okła, E and Ortega López, P and de la Mata, FJ and Waczulikova, I and Ionov, M and Bryszewska, M and Miłowska, K},
title = {Hemocompatibility of Carbosilane Dendrimers as a Therapeutic siRNA Delivery System across Blood-Brain Barrier.},
journal = {ACS applied materials & interfaces},
volume = {},
number = {},
pages = {},
doi = {10.1021/acsami.5c12952},
pmid = {41664462},
issn = {1944-8252},
abstract = {The development of nanocarriers offers a promising strategy for the delivery of therapeutics to the central nervous system. However, the clinical translation of nanosystems hinges on their interactions with blood components, which not only dictate their biodistribution and therapeutic efficacy but also may pose potential risks to hemostasis. In this study, we assess the hemocompatibility of a novel, third-generation PEGylated carbosilane dendrimer (G3Si PEG6000) and its dendriplex designed for siRNA delivery across the blood-brain barrier pertinent to Alzheimer's disease. Utilizing a comprehensive array of advanced analytical techniques, we assess cellular responses, cytokine expression, hemorheological properties, hematological parameters, and coagulation dynamics within a physiologically relevant environment. Our findings demonstrate that the investigated nanosystem elicits changes in blood rheology, immune recognition, and the intrinsic coagulation cascade, yet these effects remain below thresholds associated with clinically significant adverse outcomes. Hemolysis was ∼8-fold lower for dendriplexes than the dendrimer in PBS at the highest concentration (accordingly 3.5 ± 0.14% vs 27.46 ± 4.66%, 24 h), in 55% plasma, both formulations were nonhemolytic across all concentrations. Whole blood viscosity increased by up to ∼11% (dendrimer) and ∼16% (dendriplex) relative to the control. At 10 μM, the dendrimer approximately doubled the aPTT, whereas the corresponding dendriplex increased the aPTT by ∼30% of the control. Importantly, neither adverse effects on red blood cell and platelet indices nor toxicological responses in white blood cells were observed under the tested conditions. These findings not only support the translational potential of the studied nanosystem for therapy but also emphasize the critical role of the therapeutic cargo and the formation of a biomolecular corona in shaping the nanocarrier's biological identity and its subsequent interactions within the bloodstream. The results provide a compelling scientific basis for advancing this platform in further investigations.},
}

@article {pmid41664377,
year = {2026},
author = {Wen, H and Dong, Y and Wang, R},
title = {Hesperetin Early Intervention Reduces Β-Amyloid Production in APP/PS1 Mice by Decreasing Beta and Gamma-Secretase Enzyme.},
journal = {CNS & neurological disorders drug targets},
volume = {},
number = {},
pages = {},
doi = {10.2174/0118715273400444251015050402},
pmid = {41664377},
issn = {1996-3181},
abstract = {

Introduction: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by β-amyloid (Aβ) plaque accumulation and cognitive decline. Early intervention targeting Aβ production may mitigate AD progression. This study investigated the neuroprotective effects of hesperetin, a citrus flavonoid, in APPswe/PS1dE9 transgenic mice.

Methods: APPswe/PS1dE9 mice (3 months old) were administered hesperetin (20, 40, and 80 mg/ kg/day) for 6 months. Cognitive function was assessed using the Morris water maze and the Barnes maze. Neuronal morphology in the hippocampal CA1 region was examined using thionin staining. Aβ40, Aβ42, β-secretase, and γ-secretase levels in brain tissue and serum were measured by ELISA, and tau protein expression was analyzed by Western blotting.

Results: Hesperetin-treated mice exhibited improved learning and memory, reduced neuronal degeneration, and lower tau expression. Brain tissue showed decreased Aβ40, Aβ42, and secretase levels, whereas serum Aβ levels increased, suggesting enhanced Aβ clearance.

Discussion: Hesperetin may attenuate AD pathology by inhibiting β- and γ-secretase activity, reducing Aβ production, and promoting Aβ efflux to peripheral circulation.

Conclusion: Early hesperetin intervention demonstrates potential as a therapeutic strategy for AD by modulating Aβ metabolism and preserving cognitive function.

@article {pmid41664344,
year = {2026},
author = {Cao, J and Song, J and Yin, Z and Tang, Z},
title = {Lysine demethylase 1A alleviates Alzheimer disease progression by regulating the leucine carboxyl methyltransferase 1/protein phosphatase 2 catalytic subunit alpha/transcription factor EB pathway via O-GlcNAcase-mediated forkhead box transcription factor A2 O-GlcNAcylation modification.},
journal = {British journal of pharmacology},
volume = {},
number = {},
pages = {},
doi = {10.1111/bph.70289},
pmid = {41664344},
issn = {1476-5381},
support = {21042230044//2023 Postdoctoral Project in Heilongjiang Province/ ; //The Postdoctoral Fellowship Program of CPSF and Innovative Scientific Research Foundation of the First School of Harbin Medical University/ ; GZC20230639//National Postdoctoral Researcher Support Program, Category B/ ; },
abstract = {BACKGROUND AND PURPOSE: Lysine demethylase 1A (KDM1A; LSD1) plays anti-ferroptosis role and has been confirmed to be lowly expressed in Alzheimer disease (AD). This study explores whether LSD1 affects the progression of AD by regulating ferroptosis and related mechanisms involved.

EXPERIMENTAL APPROACH: AD mice (APP/PS1 double transgenic) were injected with adeno-associated virus expressing LSD1 overexpression vector, or siRNA against leucine carboxyl methyltransferase 1 (LCMT1)/transcription factor EB (TFEB). SH-SY5Y cells were treated with Aβ1-42 to establish an AD cell injury model. The levels of lipid peroxidation and ferroptosis-related markers were tested to evaluate ferroptosis. The protein levels of LSD1, O-GlcNAcase (OGA), forkhead box transcription factor A2 (FOXA2), LCMT1, protein phosphatase 2A catalytic subunit alpha (PP2A) and TFEB were detected by western blot. The mRNA levels of LSD1 and OGA were assessed using quantitative real-time PCR. Interactions between targets were measured by ChIP-qPCR, DNA pull down, co-immunoprecipitation and dual-luciferase reporter assay.

KEY RESULTS: LSD1 upregulation suppressed neuronal ferroptosis to attenuate AD progression in mice. Further, LSD1 overexpression alleviated Aβ1-42-induced cell injury by reducing OGA transcription and expression. OGA inhibited FOXA2 O-GlcNAcylation modification to promote its expression and transcriptional activity. Also, FOXA2 repressed LCMT1-mediated the activation of PP2A and TFEB. Furthermore, LSD1 alleviated AD process by inhibiting neuronal ferroptosis through the regulation of OGA/FOXA2/LCMT1/PP2A/TFEB axis.

CONCLUSIONS AND IMPLICATIONS: Overall, LSD1 restrained neuronal ferroptosis to alleviate the progression of AD by regulating LCMT1/PP2A/TFEB pathway via OGA-mediated FOXA2 O-GlcNAcylation modification, providing novel mechanistic insights into the deeper understanding of AD pathogenesis and the development of potential drug targets.},
}

@article {pmid41664331,
year = {2026},
author = {Siddiqui, S and Tufail, P and Khan, F and Khalid, MF and Khalid, F},
title = {Protocatechuic Acid Alleviates Neurodemyelination by Modulating PKCα-p38/MAPK Pathways in an LPC-Induced Model of Neurodegeneration.},
journal = {Current protein & peptide science},
volume = {},
number = {},
pages = {},
doi = {10.2174/0113892037385148251207081917},
pmid = {41664331},
issn = {1875-5550},
abstract = {INTRODUCTION: Neuroinflammation, axonal damage, and alterations in extracellular matrix (ECM) protein expression are hallmarks of neurodegenerative diseases. Therapies that enhance recovery from brain injury are of significant clinical value. Therefore, this study investigated the antiinflammatory properties of protocatechuic acid (PCA).

METHODS: Neuroglial cocultures were prepared from P0-P1 rats. Demyelination was induced using LPC (0.003%). The effects of PCA (10 and 25 μg) on neurite outgrowth were assessed using morphometry software. Expression of COX-2, NF-κβ, PKC-α, and p38/MAPK was examined through immunostaining, SDS-PAGE, and Western blotting. Expression intensities were quantified using ImageJ software. Sustained repetitive neuronal firing was evaluated using the patch-clamp technique.

RESULTS: PCA increased neurite outgrowth in LPC-treated cultures after 72 hours in vitro. LPCinduced upregulation of ECM proteins TN-C, LN, and CSPGs was significantly reduced by PCA treatment compared with LPC controls. Similarly, PCA decreased the expression intensities of the pro-inflammatory markers NF-κβ and COX-2 relative to LPC controls. Furthermore, PCA reversed the sustained neuronal firing pattern observed in untreated LPC-exposed neurons.

DISCUSSION: Purified bioactive compounds commonly present in everyday foods show therapeutic potential for Parkinson's and Alzheimer's diseases due to their lower toxicity compared with conventional drugs. Artificial intelligence tools, such as AlphaFold and RoseTTAFold, further support drug development by predicting PCA binding modes with PKCα and P38/MAPK, thereby contributing to the design of personalized therapeutics and advancing neuroscience research.

CONCLUSION: PCA alleviated neuroinflammation by reducing phosphorylation of PKCα and p38/MAPK.},
}

@article {pmid41664091,
year = {2026},
author = {van der Nulft, V and Stoppelenburg, A and Mahieu, LAI and Hoffstädt, HE and van der Steen, JT and van Vliet, LM and van der Linden, YM},
title = {Factors influencing readiness for advance care planning in dementia: a qualitative interview study.},
journal = {BMC palliative care},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12904-026-02012-4},
pmid = {41664091},
issn = {1472-684X},
support = {10200012110006/ZONMW_/ZonMw/Netherlands ; },
}

@article {pmid41664080,
year = {2026},
author = {García-González, J and Cote, AC and Garcia-Gonzalez, S and Liou, L and O'Reilly, PF},
title = {The gene expression landscape of disease genes.},
journal = {Genome biology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13059-026-03958-7},
pmid = {41664080},
issn = {1474-760X},
support = {30749//Brain & Behavior Research Foundation/ ; 1K99HG013547-01/HG/NHGRI NIH HHS/United States ; R01MH122866/NH/NIH HHS/United States ; },
abstract = {BACKGROUND: Fine-mapping and gene-prioritisation techniques applied to the latest genome-wide association study (GWAS) results have prioritised hundreds of genes as causally associated with disease. Here we leverage these recently compiled lists of high-confidence causal genes to interrogate where in the body disease genes operate, providing a more direct approach than previous studies, which have primarily relied on the enrichment of GWAS signals among genes with cell- or tissue-specific expression.

RESULTS: By integrating GWAS summary statistics, gene prioritisation results, and RNA-seq data from 46 tissues and 204 cell types, we directly analyse the gene expression of putative disease genes across the body in relation to 11 major diseases and cancers. In tissues and cell types with established disease relevance, disease genes show higher and more specific gene expression compared to control genes. Moreover, we detect elevated expression in tissues and cell types without previous links to the corresponding disease. While some of these results may be explained by cell types that span multiple tissues, such as macrophages in brain, blood, lung and spleen in relation to Alzheimer's disease (P-values < 10[-3]), the cause for others is unclear and warrants further investigation. To support functional follow-up studies of disease genes, we identify technical and biological factors influencing their expression. Finally, we highlight tissue-disease pairs in which significantly elevated expression is associated with increased odds of inclusion in drug development programmes.

CONCLUSIONS: We provide our systematic testing framework as an open-source, publicly available tool that can be utilised to offer novel insights into the genes, tissues and cell types involved in any disease, with the potential for informing drug development and delivery strategies.},
}

@article {pmid41663782,
year = {2026},
author = {Lee, JW and Hasegawa, T and Ikedo, A and Mizuno, K and Amizuka, N and Kong, SW},
title = {Lithium and the Brain-Bone Axis: A Bridge between Osteoporosis and Alzheimer's Disease.},
journal = {Current osteoporosis reports},
volume = {24},
number = {1},
pages = {7},
pmid = {41663782},
issn = {1544-2241},
support = {23K09116//Japan Society for the Promotion of Science/ ; R01NS129188//National Institute of Health/ ; },
mesh = {Humans ; *Alzheimer Disease/metabolism/drug therapy ; *Brain/metabolism/drug effects ; *Osteoporosis/metabolism/prevention & control/drug therapy ; Bone Density/drug effects ; *Bone and Bones/drug effects/metabolism ; Glycogen Synthase Kinase 3 beta/metabolism ; Wnt Signaling Pathway/drug effects ; *Lithium/pharmacology/therapeutic use ; Bipolar Disorder/drug therapy ; beta Catenin/metabolism ; *Lithium Compounds/pharmacology/therapeutic use ; Osteocalcin/metabolism ; },
abstract = {PURPOSE OF REVIEW: We evaluate the converging evidence positioning lithium as a systemic modulator of bone and brain health through shared molecular pathways. This review examines the molecular basis, preclinical data, and clinical observations suggesting that lithium-long established as first-line therapy for bipolar disorder-may simultaneously protect against osteoporosis and neurodegeneration as two clinical conditions increasingly recognized to share biological substrates.

RECENT FINDINGS: Lithium inhibits glycogen synthase kinase-3β (GSK-3β), stabilizes β-catenin, and activates Wnt signaling in neurons and osteoblasts, while also modulating calcium-inositol homeostasis and suppressing NF-κB-mediated inflammation. Large observational studies report lower dementia incidence and reduced fracture risk in long-term lithium users, together with increases in bone mineral density. Declining brain lithium concentrations in patients with Alzheimer's disease raise the hypothesis that lithium may act as an essential micronutrient rather than solely a pharmacological agent. Bidirectional brain-bone crosstalk involving osteocalcin signaling and sclerostin transport across the blood-brain barrier provides a mechanistic basis for these pleiotropic effects. Lithium offers a unique paradigm for understanding and potentially treating age-related decline in multiple organ systems at subclinical dosage and concentration. However, observational study limitations, optimal dose uncertainties, and toxicity related to long-term usage concerns necessitate rigorous randomized controlled trials before broader clinical recommendations can be made. Future research should focus on optimizing formulation and patient selection to realize lithium's dual protective potential for bone and brain while minimizing risk.},
}

Humans
*Alzheimer Disease/metabolism/drug therapy
*Brain/metabolism/drug effects
*Osteoporosis/metabolism/prevention & control/drug therapy
Bone Density/drug effects
*Bone and Bones/drug effects/metabolism
Glycogen Synthase Kinase 3 beta/metabolism
Wnt Signaling Pathway/drug effects
*Lithium/pharmacology/therapeutic use
Bipolar Disorder/drug therapy
beta Catenin/metabolism
*Lithium Compounds/pharmacology/therapeutic use
Osteocalcin/metabolism

@article {pmid41663779,
year = {2026},
author = {Roy, KK and Kumari, R and Upadhyay, AK and Mohanty, S},
title = {Tailoring treatments: pharmacogenomics in the management of neurodegenerative diseases.},
journal = {Acta neurologica Belgica},
volume = {},
number = {},
pages = {},
pmid = {41663779},
issn = {2240-2993},
abstract = {Neurodegenerative diseases like Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis are growing more common worldwide, yet treatment is still poor. Conventional therapies can have unforeseen side effects, produce poor medication reactions, and take longer to work. This persistent treatment gap highlights the need for novel approaches to these disorders' complex distinctions. Pharmacogenomics, which examines how genetic differences affect drug response, is a promising new subject and an urgent solution. Pharmacogenomics tailors medicine selection and administration to each patient's genetic profile, addressing the main causes of poor treatment response and preventable side effects. This research has enabled precision medicine that can improve neurodegenerative disease therapy and reduce harm. In this in-depth research, we examine neurodegenerative disease management issues, pharmacogenomics breakthroughs, and how incorporating genetics to clinical practice can improve outcomes. We examine the latest evidence that genetics affect drug breakdown, efficacy, and toxicity. We also discuss the challenges and opportunities of applying this knowledge. Pharmacogenomic approaches must be widely applied to make medicines for these awful disorders safer, more effective, and really suited to patient needs, according to our compilation.},
}

@article {pmid41663727,
year = {2026},
author = {Pusparani, Y and Lin, CY and Jan, YK and Liau, BY and Lin, FY and Furqon, EN and Talal, M and Pravin, SC and Tsai, ZR and Lung, CW},
title = {Evaluation of deep learning models for segmentation of hippocampus volumes from MRI images in Alzheimer's disease.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-38220-4},
pmid = {41663727},
issn = {2045-2322},
support = {NSTC 114-2923-E-468-001-MY3//National Science and Technology Council of Taiwan/ ; },
}

@article {pmid41663665,
year = {2026},
author = {Kang, IK and Lee, S and Moon, TK and Han, AR and Yu, DB and Jung, M and Kwak, C and Seo, JK and Rhee, HW and Kim, SW and Woo, HN and Mun, JY and Lee, H},
title = {Proximity labeling unveils potential roles of the Miro2-CISD1 network in mitochondrial dynamics and neuronal differentiation.},
journal = {Communications biology},
volume = {9},
number = {1},
pages = {195},
pmid = {41663665},
issn = {2399-3642},
mesh = {*Mitochondrial Dynamics ; Animals ; *Neurogenesis ; *Neural Stem Cells/metabolism/cytology ; *Cell Differentiation ; Humans ; *rho GTP-Binding Proteins/metabolism/genetics ; Mitochondria/metabolism ; *Neurons/metabolism/cytology ; Hippocampus/cytology/metabolism ; Mice ; *Mitochondrial Proteins/metabolism/genetics ; },
abstract = {Adult hippocampal neurogenesis, crucial for maintaining neural homeostasis, is integral to neurodegeneration. We previously identified Miro2 as a key regulator of mitochondrial dynamics and survival in hippocampal neural stem cells with potential relevance to Alzheimer's disease. Here, using TurboID-based proximity labeling, we explore Miro2's interaction networks and identify sixty-six unique interactors specific to hippocampal neural stem cells. Functional enrichment analysis reveals that these proteins are crucial for mitochondrial organization, transport, and neurodegeneration. CISD1 emerges as a significant interaction partner. Knockdown of Miro2 and CISD1 impairs mitochondrial trafficking in adult hippocampal stem cells, disrupted stem cell differentiation with increased cytotoxicity. Rescue experiments partially reverse cell death, and both Miro2 and CISD1 show increased expression and interaction during differentiation. These findings suggest the Miro2-CISD1 axis as a critical regulator of mitochondrial remodeling and neurogenesis, providing a framework for future studies on how mitochondrial dynamics contribute to neurodegenerative disease mechanisms.},
}

*Mitochondrial Dynamics
Animals
*Neurogenesis
*Neural Stem Cells/metabolism/cytology
*Cell Differentiation
Humans
*rho GTP-Binding Proteins/metabolism/genetics
Mitochondria/metabolism
*Neurons/metabolism/cytology
Hippocampus/cytology/metabolism
Mice
*Mitochondrial Proteins/metabolism/genetics