@article {pmid41082159,
year = {2025},
author = {Ntondini, TL and Naki, T and Alven, S},
title = {The therapeutic efficacy of nanoparticles in the treatment of alzheimer's disease.},
journal = {Acta neurologica Belgica},
volume = {},
number = {},
pages = {},
pmid = {41082159},
issn = {2240-2993},
abstract = {The build-up of beta-amyloid plaques in the brain leads to Alzheimer's disease (AD), a neurodegenerative condition. AD affects more than 30 million individuals globally every year. No cure for AD has been discovered yet. The available therapeutic options are administered to slow down the progress of the disease. The currently available treatment plans are used to relieve symptoms and improve cognitive abilities, thus slowing progression. Nanotechnology is highly effective and has demonstrated significant benefits across various medical applications. Nanoparticles have been explored as promising drug delivery systems for the targeted delivery of anti-AD therapeutics and for the precise diagnosis of the condition. Nanoparticles, such as dendrimers, lipid-based nanoparticles, polymer-based nanoparticles, and metal-based nanoparticles, have been designed and reported to inhibit Aβ aggregation, fibril formation, and disaggregating mature fibrils, prevent neuroinflammation and Aβ1-42-induced cell damage, treat oxidative stress and lower hallmark of Aβ, and display excellent capability to bypass blood-brain barrier (BBB). This review is focused on the preclinical therapeutic outcomes of nanoparticles and the challenges encountered in the treatment of AD. This review highlights the significant advancements of nanoparticles that are currently undergoing clinical trials for management of AD.},
}

@article {pmid41082137,
year = {2025},
author = {Aktan Süzgün, M and Tang, Q and Stefani, A},
title = {Sleep Abnormalities and Risk of Alzheimer's Disease.},
journal = {Current neurology and neuroscience reports},
volume = {25},
number = {1},
pages = {67},
pmid = {41082137},
issn = {1534-6293},
mesh = {Humans ; *Alzheimer Disease/epidemiology/physiopathology ; *Sleep Wake Disorders/complications/epidemiology/physiopathology ; Risk Factors ; },
abstract = {PURPOSE OF REVIEW: This review aimed at investigating sleep abnormalities as risk factors for Alzheimer's disease (AD), with a focus on their potential utility in early disease detection and risk modification.

RECENT FINDINGS: Impaired sleep quality, circadian misalignment, and disruptions in sleep architecture are significantly associated with an elevated risk of AD. Moreover, excessive or insufficient sleep, reductions in slow-wave and REM sleep, and fragmented rest-activity rhythms have been linked to early alterations in amyloid-β and tau biomarkers, even in cognitively unimpaired individuals. Various sleep disorders have also been identified as independent contributors to AD risk, particularly among genetically susceptible populations. Sleep and circadian disturbances, as well as changes in sleep architecture, represent easily detectable and modifiable risk factors for Alzheimer's disease. Integrating sleep and sleep-based metrics into preventive strategies may enhance early identification and offer novel avenues for intervention, modulating the risk of Alzheimer's disease.},
}

Humans
*Alzheimer Disease/epidemiology/physiopathology
*Sleep Wake Disorders/complications/epidemiology/physiopathology
Risk Factors

@article {pmid41081872,
year = {2025},
author = {Tran, HA and Weber, D and Grune, T},
title = {[Micronutrients in old age-physiological specificities and nutritional status].},
journal = {Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz},
volume = {},
number = {},
pages = {},
pmid = {41081872},
issn = {1437-1588},
abstract = {Aging is a biological and degenerative process with numerous changes in molecular and cellular mechanisms in various organ systems. These changes result in a progressive loss of anatomical structures and physiological functions. Among others, they occur in the cardiovascular system, gastrointestinal tract, skin, muscles, bones, respiratory tract, immune system, endocrine systems, and the brain. The alterations in aging can lead to diseases such as coronary heart disease, sarcopenia, osteoporosis, Alzheimer's disease, and cancer. To delay these age-related alterations and thus prevent diseases, a healthy lifestyle with a balanced diet is important. An adequate diet includes the sufficient intake of micronutrients. This article first provides an overview of physiological characteristics of aging and then addresses the supply of micronutrients in old age.In older age, the supply of vitamin D, vitamin B12, magnesium, iron, folate, and calcium may be critical. These micronutrients play a role in the immune system, bone metabolism, cell metabolism, energy production, and many other metabolic processes. Micronutrient deficiencies can enhance the aging process. Healthy older people should use the German Nutrition Society (DGE) reference values to meet their daily micronutrient needs. Older people with illnesses should follow the reference values of the guidelines for their specific illnesses to cover their micronutrient needs.},
}

@article {pmid41081870,
year = {2025},
author = {Zhang, J and Ou, J and Lu, X and Wang, T and Dang, W and Ding, L and Liu, Y and Xu, J and Yan, B and Yu, H},
title = {Sleep disorders and the risk of cognitive decline or dementia: an updated systematic review and meta-analysis of longitudinal studies.},
journal = {Journal of neurology},
volume = {272},
number = {10},
pages = {689},
pmid = {41081870},
issn = {1432-1459},
mesh = {Humans ; *Dementia/epidemiology/etiology ; *Cognitive Dysfunction/epidemiology/etiology ; *Sleep Wake Disorders/epidemiology/complications ; Longitudinal Studies ; Risk Factors ; },
abstract = {BACKGROUND: The evidence on the relationship between sleep disorders and the risk of cognitive decline or dementia remains inconsistent.

OBJECTIVES: This systematic review and meta-analysis aimed to provide updated evidence on the association between sleep disturbances and cognitive decline.

METHODS: PubMed, EMBASE, and Web of Science were systematically searched from their respective inceptions to 18 February 2025. Cohort studies investigating longitudinal associations between sleep disorders and cognitive decline or dementia were included. Pooled relative risks (RRs) with 95% confidence intervals were calculated. Sensitivity analyses were conducted to evaluate the robustness of the pooled estimates. Publication bias was assessed using Egger's and Begg's tests, and meta-regression analysis was performed to explore potential sources of heterogeneity across studies.

RESULTS: Seventy-six eligible cohort studies with eight types of sleep disturbances were included in the meta-analysis. Insomnia was associated with an increased risk of dementia (RR = 1.13). Both short sleep duration (7 h; RR = 1.27) and long sleep duration (8 h; RR = 1.23 for cognitive decline, RR = 1.43 for all-cause dementia, and RR = 1.66 for Alzheimer's disease (AD) were significant risk factors for cognitive decline and dementia. Excessive daytime sleepiness significantly increased the risks of vascular dementia (VD) (RR = 1.85), all-cause dementia (RR = 1.41), and cognitive decline (RR = 1.37). Sleep-related movement disorders indicated the strongest association, markedly increasing the risk of VD (RR = 2.53). Poor sleep quality was also a significant risk factor for AD (RR = 1.24), all-cause dementia (RR = 1.17), and cognitive decline (RR = 1.18).

CONCLUSION: This meta-analysis highlights sleep management as a pivotal modifiable factor in reducing the risk of all-cause cognitive decline. Systematic screening and early intervention for sleep disturbances should be prioritized as essential preventive strategies in clinical populations.},
}

Humans
*Dementia/epidemiology/etiology
*Cognitive Dysfunction/epidemiology/etiology
*Sleep Wake Disorders/epidemiology/complications
Longitudinal Studies
Risk Factors

@article {pmid41081724,
year = {2025},
author = {Lai, PH and Chang, TC and Zhan, HT and Chao, CY and Huang, MC and Mudiyanselage, SPK and Lin, SC},
title = {Impact of Specialty and Nonspecialty Palliative Care on Quality of Dying With Alzheimer's Disease or Related Dementias: A Systematic Review and Meta-Analysis.},
journal = {Medical care},
volume = {63},
number = {11},
pages = {851-865},
doi = {10.1097/MLR.0000000000002199},
pmid = {41081724},
issn = {1537-1948},
support = {EDAHP114032//E-Da Hospital, I-Shou University/ ; },
mesh = {Humans ; *Palliative Care/methods ; *Alzheimer Disease/therapy ; *Dementia/therapy ; *Terminal Care/standards ; Patient Satisfaction ; *Quality of Health Care ; Aged ; },
abstract = {BACKGROUND: Older adults with Alzheimer's disease and related dementias can benefit from palliative care (PC). Whether specialty and nonspecialty PC have the same effect on outcomes is unclear. We examined the effects of these 2 interventions on comfort, symptom management, satisfaction with care, and potentially burdensome transitions, including hospital admission, emergency department visit, intensive care unit admission in the end-of-life, and in-hospital death.

METHODS: This PRISMA-adherent systematic review involved a search of PubMed, Medline, EMBASE, Cochrane Library, ProQuest, and CINAHL for studies published from January 1, 2013, to November 4, 2024. Primary studies that reported at least one of the 7 patient-level outcomes were included: Comfort Assessment in Dying with Dementia (CAD-EOLD), Symptom Management at the End-of-Life (SM-EOLD), Satisfaction with Care at the End-of-Life in Dementia (SWC-EOLD), hospital admissions, emergency department visits, intensive care unit admissions, and in-hospital death.

RESULTS: Nineteen articles involving 142,772 participants were included. The evidence, comprising studies of adequate to strong quality, revealed that both specialty and nonspecialty PC did not differ in terms of comfort, symptom management, or satisfaction with care. However, both approaches significantly reduced the likelihood of intensive care unit admissions and in-hospital deaths. Specialty PC was associated with decreased emergency department visits (OR 0.53, 95% CI 0.28-1.00; I2=86%).

CONCLUSIONS: Future research is needed to understand factors influencing PC interventions that can improve comfort, symptom management, and care satisfaction for these individuals and their families.},
}

Humans
*Palliative Care/methods
*Alzheimer Disease/therapy
*Dementia/therapy
*Terminal Care/standards
Patient Satisfaction
*Quality of Health Care
Aged

@article {pmid41081630,
year = {2025},
author = {Halbgebauer, S and Fazeli, B and Klose, V and Nagel, G and Rosenbohm, A and Rothenbacher, D and Bachhuber, F and Jesse, S and Otto, M and Landwehrmeyer, GB and Abdelhak, A and Petzold, A and Ludolph, AC and Tumani, H},
title = {Age-Specific Control and Alzheimer Disease Reference Curves and z-Scores for Glial Fibrillary Acidic Protein in Blood.},
journal = {Clinical chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1093/clinchem/hvaf120},
pmid = {41081630},
issn = {1530-8561},
support = {577 631//German Research Council/ ; },
abstract = {BACKGROUND: Serum glial fibrillary acidic protein (GFAP) is a biomarker for astrocytic injury and astrogliosis. Concentrations are elevated in numerous neurological disorders, including a pronounced increase in Alzheimer disease (AD). However, GFAP levels in the serum also increase with age. Consequently, the integration of GFAP levels into clinical routine and their interpretation demands age-adjusted reference values.

METHODS: Serum from 1273 subjects (952 noninflammatory and nonneurodegenerative neurological controls and 321 subjects with AD) was analyzed for GFAP using the microfluidic Ella system. Age-dependent serum GFAP reference values were estimated by additive quantile regression analysis and visualized with percentiles and z-scores.

RESULTS: AD exhibited elevated serum GFAP levels in comparison to control patients (P < 0.0001). This remained the case when the newly generated age-corrected z-scores were applied (P < 0.0001). In the control cohort, a nonlinear elevation of serum GFAP with increasing age was observed (Spearman correlation coefficient 0.62, 95% CI 0.58-0.66, P < 0.0001). In contrast, the AD cohort exhibited a more linear increase (0.16, 95% CI 0.05-0.26, P = 0.004). Age-dependent cut-offs for serum GFAP were determined for different AD age groups. The calculated areas under the curve (AUCs; 0.97) demonstrated excellent diagnostic test performance in the early-onset age group. This effect was less marked in the elderly subjects (AUC 0.72).

CONCLUSIONS: Our novel GFAP z-scores enable the integration and interpretation of serum GFAP levels in clinical practice, moving from the group to individual level. They support both intra- and interindividual interpretation of single GFAP levels in neurological diseases with astrocytic pathology, including an accurate discrimination of AD.},
}

@article {pmid41081550,
year = {2025},
author = {Krunic, A and Bellio, TA and Cohen, BZ and Labadorf, A and Stein, TD and Lin, H and Mellott, TJ and Blusztajn, JK},
title = {Brain DNA Methylation Atlas of App[NL-G-F] Alzheimer's Disease Model Mice Across Age and Region Reveals Choline-Induced Resilience.},
journal = {Aging cell},
volume = {},
number = {},
pages = {e70241},
doi = {10.1111/acel.70241},
pmid = {41081550},
issn = {1474-9726},
support = {//NIH Office of Dietary Supplements/ ; P30 AG072978/NH/NIH HHS/United States ; R01 AG045031/NH/NIH HHS/United States ; R01 AG084624/NH/NIH HHS/United States ; R21 AG 059195/NH/NIH HHS/United States ; R21 AG056901/NH/NIH HHS/United States ; RF1 AG057768/NH/NIH HHS/United States ; RF1 AG078299/NH/NIH HHS/United States ; },
abstract = {Alzheimer's disease (AD) is the most common type of dementia. Current treatments for AD are inadequate, and there is a need to design preventive strategies that would improve the resistance or resilience to AD pathology. Because aberrant brain DNA methylation (DNAm) is associated with hallmarks of AD, we tested the hypothesis that a nutritional approach using choline, an essential nutrient and methyl donor, would modulate DNAm to ameliorate AD pathologies. Previous studies showed that perinatal choline supplementation (PCS) reduced AD-like neuropathology and inflammation while improving cognitive performance in AD mouse models. Here we investigated hippocampal and cerebral cortical DNAm patterns by reduced representation bisulfite sequencing from 3 to 12 months in wild-type (WT) and App[NL-G-F] AD model mice fed a 1.1 g/kg control or 5.5 g/kg PCS diet from conception to weaning. App[NL-G-F] mice showed extensive CpG DNAm changes, which were associated with the age-dependent progression of amyloidosis. PCS induced genotype-specific DNAm patterns and reversed DNAm changes in multiple genes in App[NL-G-F] mice. By associating DNAm with matched transcriptomics, we found that DNAm in App[NL-G-F] mice correlated with the expression of microglial genes, while DNAm-associated genes modulated by PCS were related to synaptic function. Moreover, we found that methylation levels of several CpGs were associated with levels of beta amyloidosis, relating epigenetic changes to neuropathology. Overall, our data suggest that DNAm in the brain serves as an epigenetic mechanism for abnormal gene expression in App[NL-G-F] mice and indicate that PCS may promote resilience to synaptic dysfunction through modulating DNAm.},
}

@article {pmid41081549,
year = {2025},
author = {Bellio, TA and Krunic, A and Campion, MS and Dupaguntla, R and Labadorf, A and Stein, TD and Lin, H and Mellott, TJ and Blusztajn, JK},
title = {Perinatal Choline Supplementation Promotes Resilience Against Progression of Alzheimer's Disease-Like Brain Transcriptomic Signatures in App[NL-G-F] Mice.},
journal = {Aging cell},
volume = {},
number = {},
pages = {e70148},
doi = {10.1111/acel.70148},
pmid = {41081549},
issn = {1474-9726},
support = {P30 AG072978/NH/NIH HHS/United States ; R01 AG045031/NH/NIH HHS/United States ; R21 AG 059195/NH/NIH HHS/United States ; R21 AG056901/NH/NIH HHS/United States ; RF1 AG057768/NH/NIH HHS/United States ; RF1 AG078299/NH/NIH HHS/United States ; //NIH Office of Dietary Supplements/ ; },
abstract = {Alzheimer's disease (AD)-the leading cause of dementia-has no cure, inadequate treatment options, and a limited understanding of prevention measures. We have previously shown that perinatal dietary supplementation with the nutrient choline ameliorates cognitive deficits and reduces amyloidosis across the brain in App[NL-G-F] AD model mice. Here, we analyzed transcriptomic abnormalities in these mice and tested the hypothesis that they may be attenuated by perinatal choline supplementation (PCS). Wild-type (WT) and App[NL-G-F] dams consumed a diet containing 1.1 (control) or 5 g/kg (supplemented) of choline chloride from 2 weeks prior to mating until weaning. At 3, 6, 9, or 12 months of age, the offspring RNA was sequenced in the hippocampus and cerebral cortex. As compared to WT, the App[NL-G-F] mice reared on the control diet had age-dependent upregulation of expression of mRNAs and lncRNAs related to inflammation and reduced expression of mRNAs related to neuronal function. As compared to App[NL-G-F] mice on the control diet, PCS App[NL-G-F] mice increased expression of synaptic genes and downregulated inflammation-related genes starting at 6 months in the cortex; increased expression of GABAergic function and ATP metabolism genes, and decreased expression of inflammatory genes in the hippocampus at 12 months. These changes counteracted the effects of App[NL-G-F] genotype seen in mice on the control diet. The expression of many of these choline-protected genes correlated with clinical dementia rating, inflammation, and tauopathy in human postmortem dorsolateral prefrontal cortex AD samples, indicating their relevance to the disease process. The results suggest that adequate choline intake could be a preventive strategy for AD.},
}

@article {pmid41081365,
year = {2025},
author = {Habibnia, M and Catalina-Hernandez, E and Cabrerizo-Idiazabal, M and Barnadas-Rodríguez, R and Lopez-Martin, M and Peralvarez-Marin, A},
title = {Biophysical analysis of angiotensin II and amyloid-β cross-interaction in aggregation and membrane disruption.},
journal = {FEBS letters},
volume = {},
number = {},
pages = {},
doi = {10.1002/1873-3468.70185},
pmid = {41081365},
issn = {1873-3468},
support = {PID2020-120222GB-I00//Agencia Estatal de Investigación/ ; PID2021-123682OB-I00//Agencia Estatal de Investigación/ ; },
abstract = {Amyloid-β (Aβ) aggregation is a hallmark of Alzheimer's disease. Endogenous peptides in the same environment may influence Aβ aggregation via direct interaction. This study explores the cross-interaction between Aβ and angiotensin II (AngII), a neuropeptide of the renin-angiotensin system, using biophysical assays and in silico modeling. Thioflavin T fluorescence, circular dichroism, and Congo Red assays show that AngII modestly reduces Aβ aggregation and membrane disruption in a dose-dependent manner. Liposome leakage assays confirm decreased membrane disruption. Modeling suggests AngII binds preferentially to disordered Aβ conformers. These findings indicate that AngII may modulate early amyloidogenic events and contribute to amyloid homeostasis, offering insights into the interplay between neuropeptides and amyloid pathology.},
}

@article {pmid41081092,
year = {2025},
author = {Zhang, R and Wang, R and Zhai, S and Shen, C and An, Y and Liu, Q},
title = {Bioinformatic analysis and experimental validation of hub autophagy-related genes as novel biomarkers for type 2 diabetes mellitus and Alzheimer's disease.},
journal = {PeerJ},
volume = {13},
number = {},
pages = {e20143},
pmid = {41081092},
issn = {2167-8359},
mesh = {*Alzheimer Disease/genetics/diagnosis ; *Diabetes Mellitus, Type 2/genetics/diagnosis ; *Autophagy/genetics ; Humans ; Animals ; *Computational Biology/methods ; Mice ; Biomarkers/metabolism ; Protein Interaction Maps/genetics ; Gene Expression Profiling ; Databases, Genetic ; Gene Regulatory Networks ; },
abstract = {BACKGROUND & OBJECTIVES: Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) share considerable similarities in their proposed patho mechanisms. Autophagy, an intrinsic cellular process involved in the degradation of dysfunctional organelles and abnormal proteins, has been implicated in the pathogenesis of both AD and T2DM. This study aims to identify potential shared biomarkers related to autophagy in AD and T2DM by analyzing hub differentially expressed autophagy-related genes (DEARGs) and examining their potential functions.

METHODS: Gene expression profiles for AD and T2DM were acquired from the Gene Expression Omnibus (GEO) database (training sets: GSE109887 for AD and GSE104674 for T2DM; validation sets: GSE122063 for AD and GSE64998 for T2DM). Autophagy-related genes (ARGs) were extracted from multiple databases. DEARGs were identified and integrated with module genes derived from weighted gene co-expression network analysis (WGCNA) to determine key shared ARGs. Then, the STRING database was used to construct a protein-protein interaction (PPI) network, from which hub genes were identified. These hub genes were validated using independent microarray datasets through differential expression analysis, and ROC curves were generated to assess their diagnostic value. Moreover, the expression of the hub genes was validated in brain tissues of T2DM mouse models using qRT-PCR.

RESULTS: A total of 33 shared DEARGs were identified, among which 12 were designated as hub genes (ANXA5, CCND1, MAP2K1, HSPB1, BNIP3, BAG3, YAP1, MET, FBXW7, CCL2, PFKFB3, CDKN1A) in both AD and T2DM patients. Validation using other datasets confirmed that ANXA5, BAG3, and CDKN1A remained significantly upregulated, while MET remained downregulated in both AD and T2DM patients. Additionally, PFKFB3 showed an inverse expression pattern between the two diseases. The diagnostic performance of these five hub genes was assessed using ROC curves, with all five exhibiting values of area under the curve (AUC) exceeding 0.7 for T2DM in both training and validation sets. However, only MET and PFKFB3 demonstrated good diagnostic efficacy in AD patients. In animal models, qRT-PCR analysis revealed that the expression of ANXA5, BAG3, and MET was consistent with the bioinformatics results. In contrast, the expression of PFKFB3 and CDKN1A did not differ significantly between db/db model mice and db/m control mice.

CONCLUSIONS: Our integrated bioinformatics analyses, supported by preliminary experimental validations, identified several hub ARGs shared between AD and T2DM. Among these, ANXA5, BAG3, and MET exhibited consistent expression trends across datasets and experimental models, while CDKN1A and PFKFB3 showed inconsistent expression patterns. These findings underscore the complexity of autophagy-related crosstalk in AD-T2DM comorbidity and highlight the need for further research to clarify their diagnostic and therapeutic potential.},
}

*Alzheimer Disease/genetics/diagnosis
*Diabetes Mellitus, Type 2/genetics/diagnosis
*Autophagy/genetics
Humans
Animals
*Computational Biology/methods
Mice
Biomarkers/metabolism
Protein Interaction Maps/genetics
Gene Expression Profiling
Databases, Genetic
Gene Regulatory Networks

@article {pmid41081083,
year = {2025},
author = {Arruda, GS and Morris, K and Martins, A and Wang, Y and Sloan-Dennison, S and Graham, D and Quinn, SD and Martins, ER and Krauss, TF},
title = {Ultrasensitive Alzheimer's disease biomarker detection with nanopillar photonic crystal biosensors.},
journal = {Optica},
volume = {12},
number = {10},
pages = {1587-1596},
pmid = {41081083},
issn = {2334-2536},
abstract = {The recent development of drugs able to mitigate neurodegenerative diseases has created an urgent need for biomarker tests that can be readily used by practitioners. Although biomarker detection directly in patients' blood is now possible, low-cost point-of-care tests remain a challenge because relevant biomarkers, especially amyloid- β (A β) peptides, are small, they occur at very low concentrations, and detecting a single marker is insufficient. Here, we demonstrate a photonic resonant sensor able to detect 0.2 pg/ml of A β 42 and A β 40 in 1% human blood serum, equivalent to 20 pg/ml in undiluted serum, which is the clinically required level. This high performance is achieved by combining gold nanoparticle amplification with a dielectric nanopillar photonic crystal structure in a dimer configuration, while also employing an immunoassay approach for high selectivity and specificity. The design combines high resonance Q-factor, amplitude, and sensitivity, ideally suited for sensing. We also show the detection of A β 42 and A β 40 peptides in the same channel, which is highly relevant for assessing disease progress and opens a route toward multiplexing. Together with the handheld operation we have demonstrated previously, these photonic innovations make a major contribution to the ability to detect and monitor the progression of neurodegenerative diseases such as Alzheimer's.},
}

@article {pmid41081035,
year = {2025},
author = {Ashford, MT and Aaronson, A and Jin, C and Camacho, MR and Eichenbaum, J and Ulbricht, A and Alaniz, R and Sorce, J and Kannan, S and Guerrero, L and Marquez, DX and Flenniken, D and Fockler, J and Truran, D and Mackin, RS and Mindt, MR and Paredes, AM and González, HM and Weiner, MW and Nosheny, RL},
title = {Digital efforts in Spanish for enrolling Latino adults in the Brain Health Registry.},
journal = {Alzheimer's & dementia (New York, N. Y.)},
volume = {11},
number = {4},
pages = {e70096},
pmid = {41081035},
issn = {2352-8737},
abstract = {INTRODUCTION: Previous culturally informed digital inclusion efforts in English effectively enrolled Latino adults into the Brain Health Registry (BHR), an online Alzheimer's disease (AD)-related registry. Because these efforts were in English only, we did not successfully reach individuals from the U.S. Latino community whose language preference is Spanish. The English-language effort had limited success enrolling Latino participants from diverse sociodemographic backgrounds (e.g., gender, education, nativity). Therefore, we tested the hypothesis that Spanish-language efforts would increase the sociodemographic diversity of enrolled Latino participants.

METHODS: The BHR is an online registry that collects longitudinal cognitive and health data. We worked in partnership with a Latino Community Science Partnership Board to develop Spanish-language, culturally informed digital inclusion efforts, including a Spanish translation of BHR, Facebook advertisements, and culturally informed recruitment websites. Here, we (1) report on the Spanish-language digital advertisement results, (2) compare the characteristics of participants enrolled through Spanish (July 2021 through June 2022) versus English (September 2020 to June 2022) advertisements, and (3) compare the characteristics of those using the BHR assessment portal in Spanish versus in English.

RESULTS: Culturally informed Spanish-language advertisements enrolled 1059 participants, including 986 who identify as Latino. Compared to participants enrolled through culturally informed English-language efforts (N = 6985), participants enrolled via Spanish-language efforts were significantly older, had less education, and had a higher percentage of male participants and those born outside the United States. Compared to participants who opted to use the BHR website in English (N = 37,199), those who opted to use the website in Spanish (n = 1088), were significantly younger, reported fewer years of education, and more frequently self-identified as male and Latino. However, these efforts failed to increase BHR task completion.

DISCUSSION: Culturally informed digital efforts in Spanish are effective at increasing sociodemographic diversity of a Latino, digital research cohort. Similar efforts can be adapted to other studies and settings to improve the generalizability of AD research.

HIGHLIGHTS: Implemented culturally informed, Spanish-language digital enrollment efforts.The efforts enrolled 986 Latino individuals in 12 months.Compared demographics of those enrolled through Spanish versus English advertising.Spanish efforts increased enrollment of older Latino adults born outside the United States.Efforts increased enrollment but did not increase completion of study tasks.},
}

@article {pmid41080744,
year = {2025},
author = {Franco, FN and de Cassia Cardoso, L and Silva, BNM and de Araújo, GR and Chaves, MM},
title = {The antioxidant effect of resveratrol on leukocytes from patients with Alzheimer is independent of SIRT1 signaling pathway.},
journal = {Biochemistry and biophysics reports},
volume = {44},
number = {},
pages = {102291},
pmid = {41080744},
issn = {2405-5808},
abstract = {Alzheimer's Disease (AD) is the most prevalent dementia in aging. Among its aspects is cognitive and functional decline, resulting from an increase in Reactive Oxygen Species (ROS) and Nitrogen (RNS). Resveratrol (RSV) is a polyphenolic compound that has been recognized as a potent antioxidant. The objective was to verify the oxidative profile of AD in leukocytes, correlating the main oxidative parameters with the functionality of these elderly individuals and verify the antioxidant effect of RSV. For this, ROS and RNS, the antioxidant enzymes catalase and glutathione peroxidase (GPx), as well as the action of the SIRT1 on leukocytes of elderly people without and with AD, in the presence and absence of RSV, were evaluated. It was observed that RSV, despite acting in the AD group, had its antioxidant power reduced compared to the group without AD. RSV was able to increase GPx in both groups. Analyzing SIRT1, we observe the silencing of this signaling pathway in leukocytes from AD. AD was more dependent on the Katz index. Therefore, we observed that oxidative stress predisposes to an increased loss of autonomy and independence in AD and that the antioxidant effect of RSV is reduced.},
}

@article {pmid41080679,
year = {2025},
author = {Mishra, K and Tripathi, S and Tiwari, AK and Rana, R and Yadav, P and Chourasia, MK},
title = {Cerium-based nanoparticles for neurodegeneration: emerging redox therapeutics beyond pharmaceuticals.},
journal = {RSC advances},
volume = {15},
number = {45},
pages = {37540-37569},
pmid = {41080679},
issn = {2046-2069},
abstract = {Delivering therapeutic agents across the blood-brain barrier (BBB) remains a formidable hurdle in the treatment of neurodegenerative diseases, which are primarily driven by mitochondrial dysfunction, oxidative stress, and neuroinflammation. Although our understanding of these disease mechanisms has advanced, effective treatments are still limited due to the restrictive nature of the BBB. In this context, nanotechnology has emerged as a promising approach, offering engineered nanocarriers capable of traversing the BBB and enabling targeted drug delivery to the brain. Amongst the various nanomaterials explored, cerium-based nanoparticles have gained particular attention as promising candidates for neurodegenerative disease therapy. Their multifunctionality stemming from reversible redox behaviour, enzyme-mimicking activity, sustained antioxidant effects, and anti-inflammatory properties, combined with their ability to penetrate the BBB and provide neuroprotection, positions them as a powerful platform for future therapeutic strategies. This review begins with a concise overview of the shared pathological mechanisms underlying neurodegenerative diseases, highlights BBB-related drug delivery challenges, and discusses nanocarrier strategies for brain targeting, focusing on cerium-based nanoparticles. We then delved into the structural features, synthesis techniques, and distinctive redox properties of cerium-based nanomaterials, with emphasis on cerium oxide and cerium vanadate. Their therapeutic potential is explored across Alzheimer's and Parkinson's diseases, as well as in stroke, multiple sclerosis, and glioblastoma. Key insights into their physicochemical properties, BBB permeability, and neuroprotective mechanisms are provided. We also address current limitations, including nanoparticle stability, toxicity, and translational barriers, and conclude with future directions for optimizing cerium-based nanozymes in neurotherapeutics.},
}

@article {pmid41080559,
year = {2025},
author = {Wang, Z and Chen, Y and Wang, J and Xiu, W and Zhang, G and Gao, Y and Li, A and Long, P and Deng, B and He, C and Lu, F},
title = {Pro-inflammatory S100A9 contributes to retinal ganglion cell degeneration in glaucoma.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1667097},
pmid = {41080559},
issn = {1664-3224},
mesh = {Animals ; *Calgranulin B/metabolism/blood/administration & dosage ; *Glaucoma/pathology/metabolism ; *Retinal Ganglion Cells/pathology/metabolism ; Humans ; Mice ; Disease Models, Animal ; Male ; Female ; Toll-Like Receptor 4/metabolism ; Microglia/metabolism ; Mice, Inbred C57BL ; Aged ; Middle Aged ; Intraocular Pressure ; Astrocytes/metabolism ; },
abstract = {S100A9 is a pro-inflammatory protein involved in neuroinflammation and central nervous system (CNS) neurodegenerative diseases, such as Alzheimer's and Parkinson's disease. Glaucoma, the leading cause of irreversible blindness, shares common pathogenic mechanisms with CNS disorders. These parallels suggest a potential role for S100A9 in glaucoma; however, its precise contribution remains unclear. In this study, we investigated the association between S100A9 and glaucoma by enrolling 121 patients with glaucoma, administering intravitreal injections of recombinant murine S100A9 (rmS100A9), and employing an elevated intraocular pressure (EIOP)-induced glaucoma mouse model. We found that circulating S100A9 levels were elevated in patients with glaucoma and positively associated with disease stage. Retinal S100A9 expression was significantly elevated and correlated with progressive retinal ganglion cell (RGC) loss in EIOP glaucoma mice. Furthermore, intravitreal injection of rmS100A9 led to direct RGC degeneration. Both enrichment analyses and experimental validation indicated that S100A9 may contribute to glaucomatous injury by promoting neuroinflammatory responses in retinal microglia and astrocyte via activation of the Toll-like receptor 4 (TLR4) pathway. These results raise the possibility that S100A9 as a potential target for future therapeutic exploration in glaucoma.},
}

Animals
*Calgranulin B/metabolism/blood/administration & dosage
*Glaucoma/pathology/metabolism
*Retinal Ganglion Cells/pathology/metabolism
Humans
Mice
Disease Models, Animal
Male
Female
Toll-Like Receptor 4/metabolism
Microglia/metabolism
Mice, Inbred C57BL
Aged
Middle Aged
Intraocular Pressure
Astrocytes/metabolism

@article {pmid41080460,
year = {2025},
author = {Hoegy, P and Chen, YH and Lu, Q},
title = {The role of small GTPases in Alzheimer's disease tau pathologies.},
journal = {Frontiers in cellular neuroscience},
volume = {19},
number = {},
pages = {1650400},
pmid = {41080460},
issn = {1662-5102},
abstract = {Microtubule-associated protein (MAP) tau stabilizes neuronal microtubules in axonal transport and contributes to healthy synapses. In Alzheimer's disease (AD), tau proteins become hyperphosphorylated, reduce microtubule binding, and aggregate into paired helical filaments (PHFs) in neurofibrillary tangles (NFTs). Although the steps of this dysregulation of tau are well established, the mechanisms by which each step is regulated remain incompletely understood. Misfolded protein aggregates, such as amyloid β-peptides (Aβ), are degraded by autophagy and lysosomal pathways, in which small GTPases play essential roles. However, how tau aggregates and spreads from nerve cells and whether small GTPases similarly play pivotal roles are not as clear. Here we review the recent evidence to propose that small GTPases are important in tau protein posttranslational phosphorylation, aggregation, and clearance. As such, small GTPases may prove to be important therapeutic targets that can reduce the AD tau burden.},
}

@article {pmid41080454,
year = {2025},
author = {Akhtar, M and Nabi, R and Ahmed, R},
title = {Response to "Letter to the editor related to the article "Trends in mortality due to ischemic heart diseases among patients with Alzheimer's disease in the United States from 1999 to 2020. International journal of cardiology. Cardiovascular risk and prevention, 25, 200390″.},
journal = {International journal of cardiology. Cardiovascular risk and prevention},
volume = {27},
number = {},
pages = {200518},
doi = {10.1016/j.ijcrp.2025.200518},
pmid = {41080454},
issn = {2772-4875},
}

@article {pmid41080393,
year = {2025},
author = {Panigrahi, B and Sarangi, PK},
title = {Transcranial Doppler in Dementia: A Promising Tool for Early Detection and Subtyping.},
journal = {Cureus},
volume = {17},
number = {9},
pages = {e91973},
pmid = {41080393},
issn = {2168-8184},
abstract = {Dementia remains a leading cause of morbidity among older adults, and early diagnosis is crucial for timely intervention, improved outcomes, and appropriate care planning. While advanced neuroimaging techniques are considered the gold standard for early detection and subtyping, their limited availability in many regions underscores the need for accessible alternatives. Transcranial Doppler (TCD) and transcranial sonography (TCS) offer low-cost, noninvasive, and portable approaches to assess cerebral hemodynamics and structural brain changes. As evidence continues to evolve, these sonographic tools hold promise as complementary approaches to conventional imaging, particularly where advanced modalities are unavailable.},
}

@article {pmid41080271,
year = {2025},
author = {Charles, AA and Thurmann, KE and O'Neill, AC and Wang, B and Suh, LJ and Culligan, MT and Meyer, JJ and Fischione, MA and Cevallos, ME},
title = {Abnormal Internal Carotid Artery Kinking in a Cadaver: Morphogenesis and a Potential Link to Alzheimer's Disease.},
journal = {Cureus},
volume = {17},
number = {9},
pages = {e91906},
pmid = {41080271},
issn = {2168-8184},
abstract = {We report the case of a 95-year-old female cadaver with a documented history of Alzheimer's disease (AD) and an anteroinferior kinking of the right internal carotid artery (ICA). On dissection, the right ICA bifurcated at the superior one-third of C3 and demonstrated a marked kink with an inferior deviation of 45° followed by superior redirection of 60°, consistent with morphologic criteria for kinking. A digital caliper was used to obtain vessel measurements. The right ICA lumen measured 4.2 mm in diameter with a focal wall thickness of 2.5 mm, exceeding the Mannheim consensus plaque threshold of 1.5 mm and consistent with advanced atherosclerosis. No histologic sections were available to confirm carotid plaque composition, and the diagnosis of AD was based on past medical history without neuropathologic staging. Nevertheless, the coexistence of severe ICA kinking and extensive plaque formation raises the possibility that chronic vascular insufficiency contributed to the decedent's cognitive decline. This interpretation remains speculative, particularly in the context of advanced age and likely coexisting vascular risk factors. This case underscores the importance of recognizing congenital and acquired ICA anomalies during morphologic and clinical evaluation. Quantitative assessment of ICA variation may help refine diagnostic considerations in dementia and support further investigation into the vascular contributions to neurodegeneration.},
}

@article {pmid41079997,
year = {2025},
author = {Ye, X and Yan, Y and Wang, Y and Shi, J},
title = {EEG-based minimum spanning tree analysis reveals network disruptions in Alzheimer's disease spectrum: an observational study.},
journal = {Frontiers in aging neuroscience},
volume = {17},
number = {},
pages = {1604345},
pmid = {41079997},
issn = {1663-4365},
abstract = {INTRODUCTION: Alzheimer's disease (AD) is characterized by disrupted brain connectivity, but the network changes across disease stages remain poorly understood. This observational cross-sectional study investigated alterations in functional brain networks across the AD continuum using minimum spanning tree (MST) analysis of resting-state EEG (rsEEG) data.

METHODS: We analyzed rsEEG data from 65 participants (30 healthy controls, 14 mild cognitive impairment due to AD [MCI-AD], 21 AD). Phase Lag Index (PLI)-based connectivity and MST metrics (such as diameter, eccentricity, and maximum degree) were computed across five frequency bands. Group differences were assessed using Kruskal-Wallis tests, and correlations with cognitive measures, disease severity, and cerebrospinal fluid (CSF) biomarkers were examined.

RESULTS: Significant alterations in rsEEG network topology were observed across HC, MCI-AD, and AD groups. AD patients showed increased theta band connectivity (higher mean PLI, diameter, and eccentricity) and decreased beta band connectivity (lower mean PLI and eccentricity) compared to HC. MCI-AD group exhibited higher delta band maximum degree and altered beta band network organization compared to HC and AD. These network changes correlated with cognitive performance and disease severity. Beta band mean PLI and theta band eccentricity effectively discriminated between AD/MCI-AD and HC. Significant correlations were also found between specific MST metrics and CSF biomarkers (t-Tau, p-Tau, Aβ1-42).

CONCLUSION: AD progression is characterized by frequency-specific alterations in brain network topology, particularly in theta and beta bands, detectable through rsEEG-based MST analysis. These findings suggest EEG-derived network measures may serve as potential biomarkers for early AD diagnosis and monitoring disease progression.},
}

@article {pmid41079994,
year = {2025},
author = {Pang, X and Ji, Y and Hu, C and Dai, Y and Hu, P and Wu, X and Wang, K},
title = {Correction: Altered dynamic functional network connectivity patterns in Alzheimer's disease: insights into neural dysfunction.},
journal = {Frontiers in aging neuroscience},
volume = {17},
number = {},
pages = {1693649},
doi = {10.3389/fnagi.2025.1693649},
pmid = {41079994},
issn = {1663-4365},
abstract = {[This corrects the article DOI: 10.3389/fnagi.2025.1617191.].},
}

@article {pmid41079992,
year = {2025},
author = {Cong, S and Wang, M and Yan, L and Sun, L and Zheng, B and Xie, J and Yu, T and Qian, Y},
title = {Current application status of non-invasive brain stimulation techniques in Alzheimer's disease: a bibliometric analysis.},
journal = {Frontiers in aging neuroscience},
volume = {17},
number = {},
pages = {1585885},
pmid = {41079992},
issn = {1663-4365},
abstract = {OBJECTIVE: Alzheimer's disease (AD) poses a significant global public health challenge. Non-invasive brain stimulation (NIBS) has emerged as a promising therapeutic strategy and constitutes a rapidly evolving research domain for AD intervention. This study aims to synthesize recent advancements in NIBS technologies for AD through comprehensive knowledge mapping. By mapping the research landscape, identifying key trends, and analyzing collaborative networks, we seek to explore emerging frontiers and translational potential of NIBS in AD research, thereby informing evidence-based clinical practice.

METHODS: Using the Science Citation Index Expanded (SCI-E) of Web of Science Core Collection (WOSCC) database. The analysis included an evaluation of publication trends, journal distribution statistics, country/region and institutional collaboration networks, author and co-cited author networks, co-citation document networks, as well as keywords and research hotspot analysis. Then CiteSpace, GraphPad Prism, VOSviewer, Microsoft Excel and NoteExpress were used for follow-up bibliometric analysis.

RESULTS: A total of 632 studies were included in this study. Research on NIBS applications in AD peaked during 2020-2021. The predominant journals disseminating NIBS-AD research were Journal of Alzheimer's Disease, Frontiers in Aging Neuroscience, and Clinical Neurophysiology. Italy, China, and the United States led in research contributions during this period. At the institutional level, Harvard Medical School and the University of Brescia published the most. There are 529 authors in this field, among which Professor Giacomo Koch maintains a continuous academic leadership position. Keyword analysis revealed high-frequency terms, "Alzheimer's disease," "transcranial magnetic stimulation," and "mild cognitive impairment." "Impairment" and "non-invasive brain stimulation" emerged as citation burst terms from 2022 onward, signaling current investigative priorities centered on NIBS-induced cognitive modulation, therapeutic target selection, and underlying neurophysiological mechanisms.

CONCLUSION: This study comprehensively reviews current research status, hotspots and trends of NIBS in AD. The results suggest that researchers should focus on the cognitive impact of NIBS technology on AD patients, the best therapeutic targets and potential mechanisms. Strengthening global collaboration among international, institutional and scientific researchers should be promoted to promote the in-depth development of this field.},
}

@article {pmid41079917,
year = {2025},
author = {Nakagawa, Y and Sugiyama, A and Hirano, S and Namiki, M and Kuwabara, S},
title = {Cognitive-predominant spinocerebellar ataxia type 8 with posterior cingulate cortex hypoperfusion mimicking early-onset Alzheimer's disease: A case report.},
journal = {Journal of Alzheimer's disease reports},
volume = {9},
number = {},
pages = {25424823251385561},
pmid = {41079917},
issn = {2542-4823},
abstract = {Spinocerebellar ataxia type 8 (SCA8) is an autosomal dominant neurodegenerative disorder caused by CTG/CAG repeat expansion in ATXN8OS/ATXN8 genes. The primary clinical feature is cerebellar ataxia, but approximately 30% of patients present with cognitive impairment, characterized by attentional disturbances and executive dysfunction. These cognitive deficits remain poorly understood, and no functional neuroimaging studies have been reported. We report a case of SCA8 presenting predominantly with cognitive impairment and showing marked hypoperfusion in the posterior cingulate cortex (PCC) on N-isopropyl-p-[[123]I]-iodoamphetamine single-photon emission computed tomography, closely resembling early-onset Alzheimer's disease. This case suggests PCC dysfunction may contribute to cognitive decline in SCA8.},
}

@article {pmid41079916,
year = {2025},
author = {Alba, LCO and Anlacan, VMM and Navarra, CJA and Jamora, RDG},
title = {YouTube as an educational resource: Evaluating the quality and reliability of videos for family caregivers of persons living with Alzheimer's disease dementia.},
journal = {Journal of Alzheimer's disease reports},
volume = {9},
number = {},
pages = {25424823251368887},
pmid = {41079916},
issn = {2542-4823},
abstract = {BACKGROUND: YouTube is increasingly used by patients and caregivers as a source of health information. However, the quality and reliability of content on Alzheimer's disease dementia (ADD) remain uncertain.

OBJECTIVE: This study aimed to determine whether YouTube videos on ADD provide reliable and high-quality information for caregivers and to assess whether the most popular videos are also the most trustworthy.

METHODS: In December 2024, YouTube was systematically searched for ADD-related videos. Two independent physicians reviewed each video, scoring it using modified DISCERN (mDISCERN) for reliability and the Global Quality Scale (GQS) for content quality. Videos were categorized by goal and assessed for quality, accuracy, comprehensiveness, and specific content.

RESULTS: There were 117 videos included in the study. Using the mDISCERN scale, 70 videos (59.8%) were deemed with good reliability, 33 videos (28.2%) have moderate reliability, and 14 videos (12%) have poor reliability. Using the GQS, 61 videos (51.1%) have high quality, 16 videos (28%) were assessed as excellent quality, 34 videos (29%) as moderate quality, and 7 videos (6%) as low quality. Videos from academic institutions, news agency and physicians exhibited higher mDISCERN and GQS scores compared to other groups and a significant correlation was seen between mDISCERN and GQS (p < 0.001).

CONCLUSIONS: The videos on ADD produced by healthcare professionals and academic institutions have high quality and good reliability, covering disease properties, treatment choices, and patient experiences. However, video popularity does not significantly correlate with content reliability and quality.},
}

@article {pmid41079831,
year = {2025},
author = {Elyasi, F and Aarabi, M and Adelani, M and Fariborzifar, A and Azizi, M},
title = {Neuroleptic Malignant Syndrome: A Case Report of the Oldest Man in Literature.},
journal = {Clinical case reports},
volume = {13},
number = {10},
pages = {e71206},
pmid = {41079831},
issn = {2050-0904},
abstract = {A diagnosis of neuroleptic malignant syndrome (NMS) was made in a 96-year-old man, representing the oldest documented case in the existing medical literature. Even at very low doses of antipsychotic medications, older adults are more likely to develop NMS. This increased susceptibility may exacerbate other risk factors, such as preexisting neurological disorders or the concurrent use of cholinesterase inhibitors.},
}

@article {pmid41079654,
year = {2025},
author = {Leech, G and Acosta, AL and Mahato, S and Barrett, PC and Hodges, RO and McFarland, SA and Storr, T},
title = {Photoactivatable Ru(ii) polypyridyl complexes as dual action modulators of amyloid-beta peptide aggregation and Cu redox cycling.},
journal = {Chemical science},
volume = {},
number = {},
pages = {},
pmid = {41079654},
issn = {2041-6520},
abstract = {The misfolding and aggregation of the amyloid-β (Aβ) peptide is a major hallmark of Alzheimer's disease (AD), yet therapeutic strategies targeting this process have faced long-standing challenges related to efficacy and specificity. Here, we investigate two photoactivatable Ru(ii) polypyridyl complexes (RuP) that operate as dual-action modulators of AD pathology by addressing both Aβ aggregation and Cu-Aβ associated ROS generation. The RuP contain an extended planar imidazo[4,5-f] [1,10]phenanthroline ligand, which is important for pre-association with the Aβ peptide via hydrophobic and π-π interactions, as well as sterically hindered ligands 6,6'-dimethyl-2,2'-bipyridyl (6,6'-dmb) for RuP1 and 2,9-dimethyl-1,10-phenanthroline (2,9-dmp) for RuP2, which cause steric strain at the metal center. Photoactivation of the RuP results in loss of either a 6,6'-dmb or 2,9-dmp ligand exposing cis-exchangeable coordination sites for binding to the Aβ peptide, which immediately redirects the Aβ peptide away from its β-sheet-rich fibrillization pathway, promoting the formation of amorphous, off-pathway aggregates that exhibit increased sensitivity to proteolytic degradation. We find that the photoactivated RuP are closely associated with the amorphous aggregates, and that this is a common endpoint regardless of Aβ peptide aggregation state (monomer, oligomer, or fibril). Importantly, we show that the ejected ligands also inhibit the redox cycling and ROS generation of Cu-Aβ species. Together, these results highlight the potential of photoactivatable RuP as multifunctional therapeutic candidates, offering a rational approach to intercepting Aβ aggregation and Cu-mediated oxidative stress, and advancing the design of light-responsive treatments for neurodegenerative diseases.},
}

@article {pmid41079483,
year = {2025},
author = {Ali, S and Piana, M and Pardini, M and Garbarino, S},
title = {Graph neural networks in Alzheimer's disease diagnosis: a review of unimodal and multimodal advances.},
journal = {Frontiers in neuroscience},
volume = {19},
number = {},
pages = {1623141},
pmid = {41079483},
issn = {1662-4548},
abstract = {Alzheimer's Disease (AD), a leading neurodegenerative disorder, presents significant global health challenges. Advances in graph neural networks (GNNs) offer promising tools for analyzing multimodal neuroimaging data to improve AD diagnosis. This review provides a comprehensive overview of GNN applications in AD diagnosis, focusing on data sources, modalities, sample sizes, classification tasks, and diagnostic performance. Drawing on extensive literature searches across PubMed, IEEE Xplorer, Scopus, and Springer, we analyze key GNN frameworks and critically evaluate their limitations, challenges, and opportunities for improvement. In addition, we present a comparative analysis to evaluate the generalizability and robustness of GNN methods across different datasets, such as ADNI, OASIS, TADPOLE, UK Biobank, in-house, etc. Furthermore, we provide a critical methodological comparison across families of GNN architectures (i.e., GCN, ChebNet, GraphSAGE, GAT, GIN, etc.) in the context of AD. Finally, we outline future research directions to refine GNN-based diagnostic methods and highlight their potential role in advancing AI-driven neuroimaging solutions. Our findings aim to foster the integration of AI technologies in neurodegenerative disease research and clinical practice.},
}

@article {pmid41079365,
year = {2025},
author = {Li, Y and Xu, X and Tang, L and , },
title = {GAP-43 is associated with faster amyloid-associated neurodegeneration and cognitive decline in Alzheimer's disease.},
journal = {Frontiers in neurology},
volume = {16},
number = {},
pages = {1629389},
pmid = {41079365},
issn = {1664-2295},
abstract = {BACKGROUND: It has been proposed that amyloid-β (Aβ) deposition may trigger neurodegeneration and cognitive decline. The elevated levels of presynaptic growth-associated protein 43 (GAP-43) in cerebrospinal fluid (CSF) were significantly associated with Alzheimer's disease (AD). To examine whether GAP-43 was associated with faster amyloid-associated neurodegeneration or cognitive decline, it was necessary to further explore whether Aβ deposition affected CSF GAP-43 through inflammation.

METHODS: A total of 671 participants from Alzheimer's Disease Neuroimaging Initiative (ADNI) were enrolled with available baseline CSF GAP-43, microglia activation [measured by CSF soluble triggering receptor expressed on myeloid cells (sTREM2) and progranulin (PGRN)], neurodegeneration (measured by CSF t-tau), and Aβ pathology (measured by amyloid-PET). To compare CSF GAP-43 levels across different Aβ and clinical stages, the analysis of variance (ANOVA) and Bonferroni post hoc tests were conducted. Multiple linear regression models were used to explore the association of CSF GAP-43 with sTREM2, PGRN, amyloid-PET, p-tau, t-tau and cognitive measures at baseline. Moreover, mediation models with 10,000 bootstrapped iterations were performed to investigate whether CSF GAP-43 was related to accelerated amyloid-associated neurodegeneration, then further contribute to cognitive decline, and how Aβ deposition affected CSF GAP-43 leading to neurodegeneration.

RESULTS: Compared with the amyloid- (A-) group, CSF GAP-43 was significantly higher at baseline in the amyloid+ (A+) group. When stratified by diagnosis, similar results were observed in A+ cognitively normal (CN) and A+ mild cognitive impairment (MCI), compared with A-CN or A-MCI participants. We found that baseline of CSF GAP-43 was positively related to CSF sTREM2, PGRN, amyloid-PET and t-tau, whereas it was negatively associated with cognition. Besides, CSF GAP-43 mediated the faster progression of amyloid-associated neurodegeneration and cognitive decline. Furthermore, the mediation analysis revealed that CSF sTREM2/PGRN was related to CSF t-tau mediated by CSF GAP-43 in the A+ group.

CONCLUSION: Our findings provided evidence that CSF GAP-43 was related to the accelerated amyloid-associated neurodegeneration, and further contributed to cognitive decline. We also demonstrated that Aβ deposition may act as a trigger for synaptic dysfunction by promoting inflammation.},
}

@article {pmid41079349,
year = {2025},
author = {Gallingani, C and Tondelli, M and Vannini, P and Zamboni, G},
title = {The association between anosognosia and neuropsychiatric symptoms in neurodegenerative dementias: a narrative review.},
journal = {Frontiers in neurology},
volume = {16},
number = {},
pages = {1649627},
pmid = {41079349},
issn = {1664-2295},
abstract = {Anosognosia, or unawareness of disease, is a common clinical feature in neurodegenerative dementias. Frequently reported as an early symptom, its presence has been associated with faster dementia progression and greater cognitive impairment. Similarly, neuropsychiatric symptoms (NPS) encompass non-cognitive behavioral and psychiatric disturbances that commonly affect individuals with dementia. Both aosognosia and NPS are clinically relevant in neurodegenerative diseases due to their significant implications in disease management and caregiver burden. In this narrative review, we examined studies investigating the direct relationship between anosognosia and NPS across different neurodegenerative dementias, including Alzheimer's Disease (AD), Frontotemporal Dementia (FTD) and α-synucleinopathies, such as Parkinson's Disease (PD) and Dementia with Lewy Bodies (DLB). A total of 46 studies were identified, the majority of which focused on AD. Despite considerable heterogeneity in participant selection, assessed domains, and measures of anosognosia and NPS investigated, consistent association emerged between anosognosia and global NPS scores as well as individual symptoms. Across studies, the most common finding was a negative association between anosognosia and depression and a positive association between anosognosia and apathy. Possible underlying mechanisms and shared neuroanatomical substrates of these findings are discussed. The review provides a deepened insight into key symptoms with critical implications for dementia research, clinical management, and caregiving strategies.},
}

@article {pmid41079223,
year = {2025},
author = {Hecker, J and Prokopenko, D and Lee, S and Lutz, SM and Tanzi, RE and Lange, C},
title = {FBAT DAP-G: fine-mapping of genetic associations in family-based studies using the Deterministic Approximation of Posteriors algorithm.},
journal = {Bioinformatics advances},
volume = {5},
number = {1},
pages = {vbaf233},
pmid = {41079223},
issn = {2635-0041},
abstract = {MOTIVATION: Family-based study designs enable genetic association analyses that are robust against population stratification and admixture. The Family-Based Association Test (FBAT) framework extended and generalized the Transmission Disequilibrium Test concept for trios (affected offspring and their parents) to general pedigrees, arbitrary phenotypes, and multi-variant analyses. Following the successful identification of disease susceptibility loci in classical family studies, FBAT approaches can be a valuable tool in modern large-scale biobanks that contain significant proportions of related individuals, often with heterogeneous genetic ancestries. However, recent methods for established downstream analyses, such as statistical fine-mapping, are primarily tailored towards genetic association results obtained from regression models in unrelated individuals, and suitable methodologies for FBAT results have not been established in the literature. Here, we introduce and implement a framework for statistical fine-mapping in FBAT-based family-based association studies.

RESULTS: Our approach is based on the established Deterministic Approximation of Posteriors algorithm and utilizes the association z-scores obtained from FBAT. We illustrate the method in simulation studies and an application to the Apolipoprotein E locus in a family-based association study of Alzheimer's Disease.

The fine-mapping approach FBAT DAP-G is implemented in the FBAT package https://github.com/FBATsw/FBAT/. The original code of DAP-G is available at https://github.com/xqwen/dap.},
}

@article {pmid41078767,
year = {2025},
author = {Reddi Sree, R and Kalyan, M and Anand, N and Mani, S and Gorantla, VR and Qoronfleh, MW and Sakharkar, MK and Song, BJ and Chidambaram, SB},
title = {Correction to "Newer Therapeutic Approaches in Treating Alzheimer's Disease: A Comprehensive Review".},
journal = {ACS omega},
volume = {10},
number = {39},
pages = {46197},
doi = {10.1021/acsomega.5c04637},
pmid = {41078767},
issn = {2470-1343},
abstract = {[This corrects the article DOI: 10.1021/acsomega.4c05527.].},
}

@article {pmid41078611,
year = {2025},
author = {Ye, S and Xu, W and Jiang, Z and Zhan, Y and Shen, Y and Su, L and Yang, K and Ju, B},
title = {Prediction of new-onset atrial fibrillation in sepsis patients by machine learning: A systematic review.},
journal = {Digital health},
volume = {11},
number = {},
pages = {20552076251384237},
pmid = {41078611},
issn = {2055-2076},
abstract = {AIMS: New-onset atrial fibrillation (NOAF) occurs in approximately 23% of patients with sepsis and is independently associated with increased mortality. Therefore, early prediction of NOAF has significant clinical value. However, current artificial intelligence (AI) models predominantly rely on tabular data. These unimodal AI models face limitations in predicting NOAF as they fail to fully utilize the predictive potential arising from the interplay of multimodal data.

METHODS: We reviewed current Machine Learning (ML) and Deep Learning (DL) approaches for atrial fibrillation (AF) prediction. It summarizes the selected features in ML models for predicting AF in ICU patients, and the advantages of time-window selection in DL models using electrocardiogram (ECG) signals. Notably, we compared these models in terms of feature selection, prediction horizons, and performance when applied to tabular data and ECG signal features. To enhance the predictive capability of ML for NOAF in patients with sepsis, we drew inspiration from multimodal models developed for other diseases, such as Alzheimer's disease, and proposed integrating tabular data and ECG signal data within a multimodal framework.

RESULTS: This study systematically analyzed the application of ML and DL in AF prediction. After screening, 12 studies (6 ML, 6 DL) were included. ML models, based on electronic medical records (EMR) or ECG features, achieved prediction windows ranging from minutes to hours with AUCs of 0.74-0.90. DL models processing raw ECG signals extended prediction windows to days, achieving AUCs of 0.74-0.96, with performance improving with larger datasets. A Transformer-based multimodal model (integrating clinical data and ECG) was proposed to enhance AF prediction in sepsis patients, though further validation is needed for cross-modal data fusion feasibility.

CONCLUSIONS: Transitioning from unimodal predictive models to multimodal frameworks that combine tabular clinical data and raw ECG signals is feasible within the current deep-learning framework. This approach has the potential to significantly improve the early prediction capabilities of NOAF in sepsis patients.},
}

@article {pmid41078583,
year = {2025},
author = {Frentz, I and Marcolini, S and Licher, S and De Deyn, PP and Ikram, MA},
title = {Dementia risk prediction in the general population: external validation of a prediction model in the population-based LifeLines Cohort Study.},
journal = {JAR life},
volume = {14},
number = {},
pages = {100028},
pmid = {41078583},
issn = {2534-773X},
abstract = {BACKGROUND: Models for dementia prediction in primary care are necessary to identify individuals at risk for developing dementia, but their implementation in clinical practice is partly limited due to lack of external validation or use of high-cost variables. We externally validated the predictive performance of a simple yet promising dementia risk prediction model.

METHODS: We assessed discriminative ability with a c-statistic with 95 % confidence interval, using age, history of stroke, subjective memory complaints and need for assistance with a relatively complex task as predictors. This was done on 10,007 individuals that participated in the Lifelines-cohort study. Assessment of dementia in the Lifelines Cohort Study is self-reported in the follow-up questionnaires.

RESULTS: Mean follow-up at LifeLines timepoint 1b was 1.5 years, mean follow-up at LifeLines timepoint 2a was 3.3 years and mean follow-up at LifeLines timepoint 3a was 9.1 years. Overall, 36 participants self-reported dementia development. Discriminative ability of the model overall dementia development yielded a c-statistic of 0.62 [95 % CI=0.48-0.70], and performed slightly better at follow-up 2a 0.67 [95 % CI=0.57-0.78]. However, calibration of the model in this external validation cohort was poor, with systematic overestimation of the predicted risk.

CONCLUSION: In this study the basic dementia risk prediction model overestimated the risk of dementia, but had reasonable discriminative ability in the Lifelines cohort. Within this validation cohort the potential of the model is underestimated due to low incidence of reported dementia. Further validation is required to determine the true value of the model. Studies assessing its implementation feasibility in primary care should also be conducted.},
}

@article {pmid41078543,
year = {2025},
author = {Vijayaram, S and Mahendran, K and Razafindralambo, H and Ringø, E and Kannan, S and Sun, YZ},
title = {Probiotics, gut microbiota, and brain health: Exploring therapeutic pathways.},
journal = {AIMS microbiology},
volume = {11},
number = {3},
pages = {501-541},
pmid = {41078543},
issn = {2471-1888},
abstract = {The gut microbiome plays a significant role in regulating gastrointestinal (GI) function and modulating the gut-brain axis, which describes the bidirectional communication between the GI tract and the central nervous system (CNS). Its involvement in digestion, immunity, and neurophysiology is well recognized. This study offers novel insights by focusing on psychobiotics, a class of probiotics with targeted neuroactive properties. These microorganisms influence brain function through defined mechanisms, including modulation of neuroinflammation, neurotransmitter production (GABA, serotonin), regulation of the hypothalamic-pituitary-adrenal (HPA) axis, and vagus nerve signaling. Our work critically examines recent advances in applications of psychobiotics for neurological disorders such as Parkinson's disease, Alzheimer's disease, multiple sclerosis, and autism spectrum disorder. By integrating evidence from microbiome research, neuroimmunology, and clinical studies, we identify promising microbial strains and mechanistic pathways with therapeutic potential. This study contributes original perspectives by highlighting underexplored microbe-host interactions and proposing targeted microbial interventions as adjuncts to conventional neurotherapies. Further research is needed to validate strain-specific effects, long-term efficacy, and safety profiles in clinical settings.},
}

@article {pmid41078393,
year = {2025},
author = {Dastgheib, ZA and Lithgow, BJ and Moussavi, ZK},
title = {Correction: Differential impact of repetitive transcranial magnetic stimulation on alzheimer's disease symptomology: evidence from electrovestibulography.},
journal = {Cognitive neurodynamics},
volume = {19},
number = {1},
pages = {164},
doi = {10.1007/s11571-025-10355-6},
pmid = {41078393},
issn = {1871-4080},
abstract = {[This corrects the article DOI: 10.1007/s11571-025-10310-5.].},
}

@article {pmid41078388,
year = {2025},
author = {Lee, BH and Barha, CK and Chaiton, J and Lieblich, SE and Wong, S and Hodges, TE and Splinter, TFL and Hsiung, GR and Murphy, KJ and Hayden, S and Galea, LAM},
title = {Previous parity differentially influences cognition in later life depending on dementia status.},
journal = {NPJ dementia},
volume = {1},
number = {1},
pages = {29},
pmid = {41078388},
issn = {3005-1940},
abstract = {Sex influences cognitive aging and dementia, yet research on the impact of female-specific factors, such as parity and fetal sex, on later-life cognition remains limited and equivocal. Inconsistencies in the literature may reflect varying effects across cognitive domains and dementia status. This study reviewed data from female participants of the University of British Columbia Hospital Clinic for Alzheimer and Related Dementias (UBCH CARD) to examine how parity and son-to-daughter ratio affect performance on medial temporal lobe-dependent (episodic memory) and prefrontal lobe-dependent (executive function) tasks depending on dementia status. Among females with dementia, higher parity was associated with reduced episodic memory but enhanced executive function performance, whereas a greater son-to-daughter ratio was associated with reduced executive function performance. These relationships were not observed in cognitively normal females or those diagnosed with mild cognitive impairment. These results emphasize the importance of integrating sex-specific factors into research and the development of precision therapeutics.},
}

@article {pmid41078387,
year = {2025},
author = {Zapata-Restrepo, LM and Miller, BL and Rivas, J and Possin, K and Valcour, V and Piña-Escudero, SD and Ibañez, A and Kosik, KS},
title = {Case of early onset Alzheimer's disease associated with a novel PSEN1 variant identified in Colombia.},
journal = {NPJ dementia},
volume = {1},
number = {1},
pages = {31},
pmid = {41078387},
issn = {3005-1940},
abstract = {Early-onset Alzheimer's disease (EOAD) is a rare form of dementia that often progresses more quickly than late-onset cases, and is more commonly associated with autosomal dominant mutations. A 47-year-old male presented with progressive cognitive and behavioral decline, a family history of EOAD, and was later found to have a novel pathogenic PSEN1 variant (c.519 G > T, p.Leu173Phe). Initial evaluations, including neuroimaging and laboratory tests, were unremarkable. Neuropsychological testing later revealed memory impairment, executive dysfunction, and neuropsychiatric symptoms. These features, alongside the identified mutation, are consistent with phenotypic presentations of EOAD involving the third transmembrane domain of PSEN1. Pharmacological treatment with cholinesterase inhibitors and antipsychotics yielded limited benefit. Notably, the extended follow-up time, of more than 10 years from the early symptomatic stage, is a unique and valuable feature of this case study, providing rare longitudinal insight into the natural course of genetically confirmed EOAD.},
}

@article {pmid41078217,
year = {2025},
author = {Paudel, P and Sah, A and Paudel, P},
title = {ApoE Polymorphism Analysis in Health and Disease of South Asian Populations: A Systematic Review and Meta-Analysis.},
journal = {Clinical genetics},
volume = {},
number = {},
pages = {},
doi = {10.1111/cge.70064},
pmid = {41078217},
issn = {1399-0004},
abstract = {This systematic review and meta-analysis assesses the distribution and health implications of apolipoprotein E (ApoE) ε2, ε3, and ε4 alleles, which play crucial roles in lipoprotein metabolism, in South Asian populations, with a focus on neurodegenerative diseases, movement disorders, traumatic brain injury, mental health disorders, cardiovascular disorders, metabolic disorders, and trauma-related disorders. A total of 53 studies identified through comprehensive searches in PubMed, Embase, and Google Scholar up to July 31, 2024, were included on the basis of predefined eligibility criteria after Risk of Bias Assessment via the New York Ottawa Scale. ε3/ε3 was found to be the most prevalent genotype, followed by ε3/ε4 and ε2/ε3. ε4-containing genotypes were associated with susceptibility to Alzheimer's disease, coronary artery disease, vascular dementia, and obesity, though high heterogeneity in some associations necessitates cautious interpretation, whereas the ε2/ε3 and ε2 alleles showed protective effects in some conditions. These studies had several limitations, including data gaps for specific health conditions, underrepresentation of some South Asian countries, and heterogeneity in outcomes. Despite gaps in the data for some countries and specific health conditions, this review reveals distinct South Asian patterns in ApoE polymorphism-disease associations, highlighting the need for targeted genetic research and tailored public health strategies to advance personalized medicine and healthcare policies in this region. There was no specific funding for this study. The study was registered in PROSPERO (registration number CRD42024575197).},
}

@article {pmid41078215,
year = {2025},
author = {Kosa, AC and Lopez-Gutierrez, L and Ando, K and Doeraene, E and Aydin, E and Lasri, H and Wathelet-Depauw, A and Pieters, K and Van Morckhoven, D and Imbault, V and Dubois, C and Bisteau, X and Stamatopoulos, B and Igoillo-Esteve, M and Brion, JP and Leroy, K},
title = {Differential effects of age and sex on tau pathology propagation in the htau mouse model: A neuropathological and proteomic study.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21},
number = {10},
pages = {e70784},
doi = {10.1002/alz.70784},
pmid = {41078215},
issn = {1552-5279},
support = {//Fondation Recherche Alzheimer/ ; //Belgian Fonds de la Recherche Scientifique Médicale/ ; //King Baudouin Foundation/ ; //Fondation Médicale Reine Elisabeth/ ; //ULB Génicot Fund/ ; //Jaumotte-Demoulin Fund/ ; //Foundation Simone and Pierre Clerdent/ ; FX47285//Fonds De La Recherche Scientifique - FNRS/ ; },
mesh = {Animals ; *tau Proteins/metabolism/genetics ; Female ; Male ; Disease Models, Animal ; Proteomics ; Humans ; *Brain/pathology/metabolism ; Mice ; Mice, Transgenic ; *Aging/pathology/metabolism ; *Alzheimer Disease/pathology/metabolism ; Sex Factors ; Age Factors ; *Sex Characteristics ; },
abstract = {INTRODUCTION: Aging is the main risk factor for Alzheimer's disease (AD), acting through still poorly understood mechanisms. AD is associated with the development of a tau pathology, a hallmark lesion propagating in the brain along neuroanatomically connected pathways. This study investigates changes in gene expression and patterns of tau pathology after induction of tau pathology propagation and the effects of age and sex on this propagation.

METHODS: Young and old humanized htau mice were intracerebrally injected with pathological tau from human AD brain to induce tau pathology.

RESULTS: Young and old htau male mice showed similar patterns of tau pathology propagation, whereas the density of tau pathology was increased in young compared to old female mice. Proteomic analysis demonstrated differential expression of proteins involved in endocytosis, autophagosome formation, and tau splicing.

DISCUSSION: The increased tau pathology formation in young female mice suggests that involvement of selected biological mechanisms could occur early in women during their midlife to explain their sensitivity to the development of tau pathology.

HIGHLIGHTS: Tau pathology induced by human PHF-tau is mainly composed of 3R-tau in htau mice. Splicing factors favoring 4R-tau are downregulated in mice with tau pathology. Tau pathology propagation is increased in young females compared to old females. Proteins implicated in endocytosis and autophagy are modified when tau pathology propagates. Some protein expressions are similarly modified in young females and during normal aging.},
}

Animals
*tau Proteins/metabolism/genetics
Female
Male
Disease Models, Animal
Proteomics
Humans
*Brain/pathology/metabolism
Mice
Mice, Transgenic
*Aging/pathology/metabolism
*Alzheimer Disease/pathology/metabolism
Sex Factors
Age Factors
*Sex Characteristics

@article {pmid41078145,
year = {2025},
author = {Wang, F and Liu, J and Bai, D and Li, L and Fedgchin, M and Henley, D and Li, H and Zhang, F},
title = {A Phase 1 Study of the Pharmacokinetics, Safety, and Tolerability of Posdinemab (JNJ-63733657) in Healthy Chinese Adults.},
journal = {Journal of clinical pharmacology},
volume = {},
number = {},
pages = {},
doi = {10.1002/jcph.70116},
pmid = {41078145},
issn = {1552-4604},
support = {//Johnson & Johnson/ ; },
abstract = {Posdinemab, a humanized immunoglobulin G1/κ monoclonal antibody, binds with high affinity to phosphorylated tau protein which is associated with Alzheimer's disease (AD) pathophysiology. Posdinemab reduced tau seeding in murine models and was well tolerated in Phase-1 clinical studies. This open-label, single-arm, Phase-1 study examined the effects of posdinemab with single intravenous dose (60 mg/kg) in healthy adults from China. The main objectives were to assess posdinemab serum pharmacokinetics (PK, primary), safety and tolerability (secondary), and presence of anti-drug antibodies (ADAs; secondary). Results were compared with Phase-1 European first-in-human (NCT03375697) and Japanese (NCT03689153) studies. Healthy Chinese participants (N = 10), mean age 60.0 (SD 3.80) years and 60% female, received posdinemab. Mean posdinemab serum Cmax was 1401 µg/mL, median tmax was 0.08 days, mean AUCinf was 18162 µg·day/mL, mean CL was 3.36 mL/day/kg, and mean elimination t1/2 was 17.5 days. Most participants (n = 8; 80%) experienced ≥1 treatment-emergent adverse event (TEAEs), most common (20%) of which were arthralgia and back pain. Four participants (40.0%) were positive for posdinemab ADAs post-dose with peak titers of 1:22.5 (n = 3) and 1:360 (n = 1). Serum posdinemab concentrations in ADA-positive and ADA-negative participants were generally comparable. In conclusion, PK profile of posdinemab in healthy participants from China was in the expected range and comparable to previous Phase-1 studies in Europe and Japan. There were no new safety concerns. These results support further global development of posdinemab in AD.},
}

@article {pmid41078087,
year = {2025},
author = {Alcalde-Herraiz, M and Woolf, B and Xie, J and Anderson, E and Gill, D and Tzoulaki, I and Winchester, LM and Yarmolinsky, J and Prieto-Alhambra, D and Newby, D},
title = {Phosphodiesterase-5 Inhibition and Alzheimer's Disease Risk: A Mendelian Randomisation Study.},
journal = {Aging cell},
volume = {},
number = {},
pages = {e70265},
doi = {10.1111/acel.70265},
pmid = {41078087},
issn = {1474-9726},
support = {//NIHR Oxford Biomedical Research Centre/ ; },
abstract = {While preclinical studies suggest that Phosphodiesterase 5 (PDE5) inhibition may reduce cognitive impairment, findings from observational studies on whether PDE5 inhibitors reduce Alzheimer's disease (AD) risk have been inconsistent. We performed a two-sample cis-Mendelian Randomisation (MR) analysis to estimate the causal effect of PDE5 inhibition on AD risk. The analysis was performed across four different genome-wide association studies (GWAS) of AD to enhance reliability through triangulation. Additionally, a sex-stratified MR analysis using data from UK Biobank was performed to assess potential sex-specific effects. No evidence of a causal association between PDE5 inhibition and AD risk was found in the main analyses. Similar findings were obtained in the sex-stratified analysis. Our study uses genetic data to triangulate the evidence and suggests that PDE5 inhibitors are unlikely to decrease the risk of AD. Further research is needed to thoroughly understand the impact of PDE5 inhibitors on the risk of Alzheimer's disease.},
}

@article {pmid41077614,
year = {2025},
author = {La Barbera, L and Krashia, P and Loffredo, G and Cauzzi, E and De Paolis, ML and Montanari, M and Saba, L and Spoleti, E and Ficchì, S and Zaccone, C and De Bardi, M and Palazzo, C and Marino, R and Latagliata, EC and Puglisi-Allegra, S and Borsellino, G and Keller, F and Lo Iacono, L and Viscomi, MT and Nobili, A and D'Amelio, M},
title = {Midbrain degeneration triggers astrocyte reactivity and tau pathology in experimental Alzheimer's Disease.},
journal = {Molecular neurodegeneration},
volume = {20},
number = {1},
pages = {105},
pmid = {41077614},
issn = {1750-1326},
support = {GR-2019-12370446//Ministero della Salute/ ; RF-2018-12365527//Ministero della Salute/ ; AARG-22-922961/ALZ/Alzheimer's Association/United States ; AARG-21-851219/ALZ/Alzheimer's Association/United States ; AARG-18-566270/ALZ/Alzheimer's Association/United States ; },
mesh = {Animals ; *Alzheimer Disease/pathology/metabolism ; Mice ; *Astrocytes/metabolism/pathology ; *tau Proteins/metabolism ; Mice, Inbred C57BL ; Mice, Transgenic ; Disease Models, Animal ; *Mesencephalon/pathology/metabolism ; Male ; Hippocampus/metabolism/pathology ; },
abstract = {BACKGROUND: Smaller midbrain volumes predict Alzheimer's Disease (AD) progression and faster conversion from Mild Cognitive Impairment (MCI) to dementia. Along with this, various midbrain-target areas are characterized by neuroinflammation since the MCI stage. The concomitance of neuroinflammation, Αβ and tau appears to be a strong predictor for conversion from MCI to dementia. Yet, how midbrain degeneration could cause disease progression, and what mechanisms are involved in triggering neuroinflammation in midbrain-target areas such as the hippocampus remain unexplored.

METHODS: Using adult C57BL/6N mice we generated a new mouse model carrying lesions in three midbrain nuclei, the dopaminergic Ventral Tegmental Area (VTA) and Substantia Nigra pars compacta (SNpc) and the serotonergic Interpeduncular Nucleus (IPN), to evaluate the consequences of dopamine and serotonin deprivation in midbrain-target areas. We characterized this model by performing stereological cell counts, analysis of monoaminergic fibers, monoamine levels, electrophysiology and behavioral tests. We then assessed hippocampal neuroinflammation by analyzing glia cell count, changes in morphology, NLRP3 inflammasome activation and cytokine levels, and microglia transcriptional profiling. In a separate set of experiments, we induced experimental midbrain lesion in Tg2576 transgenic mice overexpressing the Swedish mutant amyloid precursor protein, to evaluate the effect of monoamine deprivation on the hippocampus in concomitance with amyloid-β (Aβ) accumulation. The lesion performed in Tg2576 mice, as opposed to that in C57BL/6N mice, provides valuable insights into how neuroinflammation is influenced by Aβ accumulation versus the exclusive impact of impaired monoaminergic signaling.

RESULTS: The concomitant depletion of dopaminergic and serotonergic inputs within the hippocampus of C57BL/6N mice provokes a pronounced activation of microglia via the NLRP3-inflammasome pathway, accompanied by increased IL-1β expression. Pharmacological intervention with either dopaminergic (L-DOPA or A68930) or serotonergic (fluoxetine) agents abrogates this neuroinflammatory response. In the Tg2576 transgenic mouse model of amyloid pathology, which exhibits progressive Aβ deposition, superimposed midbrain degeneration markedly amplifies AD-like neuropathology. This includes exacerbation of microglial reactivity, robust astrocyte response, precocious Aβ plaque burden, and induction of pathological tau hyperphosphorylation. Notably, administration of L-DOPA or fluoxetine significantly attenuates both the astrocyte reactivity and tau hyperphosphorylation in the lesioned Tg2576 cohort.

CONCLUSIONS: These results highlight the pivotal role of midbrain damage for the amplification of neuroinflammatory cascades and AD pathology. Moreover, they offer mechanistic insight into the faster progression to dementia in patients with midbrain deficits. By translating these findings into clinical practice, we can advance towards a precision medicine approach in disease management.},
}

Animals
*Alzheimer Disease/pathology/metabolism
Mice
*Astrocytes/metabolism/pathology
*tau Proteins/metabolism
Mice, Inbred C57BL
Mice, Transgenic
Disease Models, Animal
*Mesencephalon/pathology/metabolism
Male
Hippocampus/metabolism/pathology

@article {pmid41077591,
year = {2025},
author = {Zhang, W and Shi, B and Xie, Y and Li, Y and Yang, J and Zhao, K},
title = {Remimazolam alleviates hippocampal neuronal injury in an in vitro Alzheimer's disease model by promoting PINK1/Parkin-mediated mitophagy.},
journal = {European journal of medical research},
volume = {30},
number = {1},
pages = {962},
pmid = {41077591},
issn = {2047-783X},
mesh = {*Ubiquitin-Protein Ligases/metabolism/genetics ; *Alzheimer Disease/drug therapy/metabolism/pathology ; *Mitophagy/drug effects ; *Protein Kinases/metabolism/genetics ; *Hippocampus/drug effects/pathology/metabolism ; Animals ; *Neurons/drug effects/metabolism/pathology ; Mice ; Neuroprotective Agents/pharmacology ; Reactive Oxygen Species/metabolism ; Amyloid beta-Peptides ; Mitochondria/drug effects/metabolism ; Apoptosis/drug effects ; Cell Line ; Humans ; },
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the pathological accumulation of amyloid-β (Aβ) plaques and hyperphosphorylated tau proteins. Remimazolam (RMZ), a novel ultra-short-acting benzodiazepine, exhibits neuroprotective effects by enhancing mitochondrial autophagy independently of traditional GABAergic mechanisms. This study investigates the protective role of RMZ against Aβ1-42-induced neuronal damage through PINK1/Parkin-mediated mitophagy. In hippocampal HT22 cells, RMZ significantly attenuated Aβ1-42-induced cytotoxicity, reduced apoptosis, suppressed reactive oxygen species (ROS) production, and decreased lactate dehydrogenase (LDH) release. Moreover, RMZ ameliorated mitochondrial membrane depolarization and tau hyperphosphorylation, while enhancing mitophagy, evidenced by an increased LC3-II/LC3-I ratio, elevated Beclin-1 expression, and decreased P62 levels. Mechanistically, RMZ upregulated PINK1 and Parkin expression, facilitating mitochondrial recruitment and clearance of damaged mitochondria. Importantly, knockdown of PINK1 abolished RMZ's protective effects, confirming the pathway's specificity. These findings suggest that RMZ promotes mitochondrial homeostasis and offers a promising strategy for AD therapy via PINK1/Parkin-mediated mitophagy.},
}

*Ubiquitin-Protein Ligases/metabolism/genetics
*Alzheimer Disease/drug therapy/metabolism/pathology
*Mitophagy/drug effects
*Protein Kinases/metabolism/genetics
*Hippocampus/drug effects/pathology/metabolism
Animals
*Neurons/drug effects/metabolism/pathology
Mice
Neuroprotective Agents/pharmacology
Reactive Oxygen Species/metabolism
Amyloid beta-Peptides
Mitochondria/drug effects/metabolism
Apoptosis/drug effects
Cell Line
Humans

@article {pmid41077117,
year = {2025},
author = {Elamin, SA and Al Shibli, AN and Shaito, A and Al-Maadhadi, MJMB and Zolezzi, M and Pedersen, S},
title = {Anti-amyloid monoclonal antibody therapies in Alzheimer's disease - a scoping review.},
journal = {Neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neuroscience.2025.10.011},
pmid = {41077117},
issn = {1873-7544},
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder affecting millions worldwide, and with advancements in the medical field, Anti-amyloid monoclonal antibodies (AA mAbs) targeting amyloid-β have emerged as potential disease-modifying agents altering AD pathology. This scoping review mapped the characteristics, patterns, and gaps in clinical trials investigating the efficacy and safety of AA mAbs in AD treatments, with focus on cognitive, functional, biochemical, imaging, and safety outcomes. It highlighted patterns, gaps, and limitations of the existing literature. A systematic search of PubMed/MEDLINE, Embase, Scopus, and Web of Science was conducted for studies published since inception to February 2022, and eligible studies that investigated efficacy and safety outcomes of AA mAbs in treatment of AD were included. A majority of the included trials reported a combination of cognitive, functional, biochemical, and imaging outcomes. Across the sample, reductions in amyloid burden were frequently reported (10 trials), with a smaller subset of studies reporting significant cognitive and functional improvements (4 trials), primarily lecanemab and aducanumab in addition to one pooled analysis of solanezumab. ARIA-E and ARIA-H were frequently reported among the safety concerns, particularly in high-dose and APOE ε4 carrier populations. Notable limitations were observed in the reviewed literature including a disconnect between biomarker changes and consistent clinical benefits and, importantly, limited population diversity and patient-reported outcomes. This review highlights the need for rigorous, diverse, and patient-centered research. Addressing these gaps is critical in ensuring safe, effective, and equitable treatment for all patients living with Alzheimer's disease.},
}

@article {pmid41077116,
year = {2025},
author = {Escobar-López, M and Salazar-Varas, R},
title = {Analysis of EEG coherence according to the onset of Alzheimer's disease.},
journal = {Neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neuroscience.2025.09.049},
pmid = {41077116},
issn = {1873-7544},
abstract = {Alzheimer's disease (AD) is one of the most common neurodegenerative diseases, the effects of which can be slowed down by an early and correct diagnosis. Greater diagnostic accuracy depends on a better understanding of the disease. In this regard, electroencephalography is a promising low-cost tool to explore brain activity and support the diagnosis of AD. When analyzing EEG signals, age is a factor that is not usually taken into account despite being one of the main risk factors. In this work, an analysis of brain connectivity is proposed in the different frequency bands by analyzing the study groups (healthy control and Alzheimer's disease) in two separate processes according to the age of the patients (U65 and A65). The results obtained suggest that changes in brain connectivity due to AD are different depending on whether AD is present before or after the age of 65 years. Furthermore, it is observed that theta, high Alpha and high Beta are more affected for the U65 group, mainly in the frontal and parietal areas; and low Alpha, low Beta and, especially gamma are more affected for the A65 group in the frontotemporal and frontoparietal areas. Therefore, the importance of dividing the analysis by age lies in its ability to identify changes in brain connectivity based on the age at which AD occurs. Finally, using the information obtained in the analysis, a classification framework is performed to validate the EEG coherence analysis with an overall performance of 87.8% accuracy, 88.8 % sensitivity, and 87.2 % specificity.},
}

@article {pmid41076749,
year = {2025},
author = {Kunath, N and Ramfjord, HAB and Kvisvik, EV and Konyves-Kolonics, M and Rolfseng Grøntvedt, G and Serysheva, II and Komorowski, L and Wildemann, B and Jarius, S},
title = {ITPR1 autoantibody-associated autoimmunity as a cause of newly emerging cognitive decline mimicking Alzheimer's disease: Case report and brief review of the literature.},
journal = {Journal of neuroimmunology},
volume = {409},
number = {},
pages = {578774},
doi = {10.1016/j.jneuroim.2025.578774},
pmid = {41076749},
issn = {1872-8421},
abstract = {BACKGROUND: Since its first description in 2014, anti-inositol 1,4,5-trisphosphate receptor type 1 (ITPR1, also termed IP3R1) autoimmunity has been recognized as causing a clinically heterogeneous spectrum of symptoms. While first described in patients with autoimmune cerebellar ataxia, this facultative paraneoplastic disease has been associated also with peripheral neuropathy, dysautonomia, sleep disorders, neuropsychiatric/psychotic symptoms, and cognitive decline.

METHODS: Retrospective case study.

RESULTS: We report the case of a 58-year-old patient who was admitted with acute confusion, rapidly progressive cognitive decline, and hallucinations. A history of mild cognitive impairment over several years and low cerebrospinal fluid (CSF) amyloid beta-42 and elevated CSF tau protein were suggestive of Alzheimer's disease (AD). However, pleocytosis, intrathecal IgG synthesis and blood-CSF barrier dysfunction prompted screening for antineuronal antibodies, which revealed ITPR1-IgG1/anti-Sj antibodies in both serum and CSF. Brain MRI showed limbic hyperintensities and hippocampal atrophy. No neoplastic disease was found. Immunosuppressive treatment stabilized the disease course but did not lead to symptom improvement.

CONCLUSIONS: This case underscores the clinical importance of CSF analysis and testing for anti-neural autoantibodies, including less common reactivities, in case of rapid cognitive decline even in patients with known or suspected neurodegenerative disease, such as AD, with ITPR1 representing a novel autoimmune target antigen.},
}

@article {pmid41076604,
year = {2025},
author = {Ebadpour, N and Abavisani, M and Karav, S and Kesharwani, P and Sahebkar, A},
title = {Exosome/Extracellular Vesicles-Based Therapeutics in Alzheimer's Disease: Neuroprotective Roles and Future Perspectives.},
journal = {Journal of molecular neuroscience : MN},
volume = {75},
number = {4},
pages = {137},
pmid = {41076604},
issn = {1559-1166},
mesh = {*Alzheimer Disease/therapy/metabolism ; Humans ; *Exosomes/metabolism/transplantation ; *Extracellular Vesicles/metabolism/transplantation ; Animals ; },
abstract = {Alzheimer's disease (AD), a progressive neurodegenerative disorder, is marked by memory loss, cognitive decline, and characteristic pathological features including β-amyloid (Aβ) plaques, tau tangles, and neuroinflammation. Despite extensive research, effective therapies remain elusive. Exosome/EVs-based therapeutics have emerged as a promising avenue for AD treatment. Neuron-derived exosomes/extracellular vesicles (EVs) (NDEs) and stem cell-derived exosomes/EVs exhibit neuroprotective effects by promoting Aβ degradation, modulating tau pathology, and reducing inflammation. Notably, NDEs carry insulin-degrading enzyme (IDE) and cellular prion proteins (PrPC), aiding Aβ clearance. However, exosomes also present challenges, such as the potential propagation of pathogenic tau and complement-mediated neurotoxicity. Neural and mesenchymal stem cell-derived exosomes further demonstrate therapeutic efficacy by altering amyloid precursor protein processing and activating PI3K/Akt/mTOR signaling to reduce AD pathology. Despite these advancements, clinical translation requires a deeper understanding of exosome/EVs biology, improved isolation techniques, and personalized strategies. Continued research may establish exosomes as a transformative approach in AD therapy.},
}

*Alzheimer Disease/therapy/metabolism
Humans
*Exosomes/metabolism/transplantation
*Extracellular Vesicles/metabolism/transplantation
Animals

@article {pmid41076410,
year = {2025},
author = {De Lucia, N and Petraglia, L and Komici, K and Bencivenga, L and Rengo, G and Maldonato, NM and Femminella, GD and , },
title = {Mild Behavioral Impairment as a Predictor of Functional Status.},
journal = {The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jagp.2025.09.003},
pmid = {41076410},
issn = {1545-7214},
abstract = {OBJECTIVES: Mild behavioral impairment (MBI) occurs in absence of dementia, but no studies explored whether MBI may limit the individuals' ability to complete everyday tasks necessary to live independently. In this study we elucidated on the relevance of specific behavioral markers on functional decline in both cognitively normal (CN) older adults and with mild cognitive impairment (MCI), and evaluated whether individuals with MBI present worse cognition and neurodegenerative dysfunctions compared to subjects without MBI.

DESIGN: Observational cross-sectional study.

SETTING: Alzheimer's Disease Neuroimaging Initiative (ADNI) database.

PARTICIPANTS: Amnesic MCI (aMCI; n = 232) participants and CN (n = 418) individuals.

MEASUREMENTS: Neuropsychological assessment, volumetric MR brain scan, Flortaucipir PET for in vivo assessment of regional tau deposition, functional assessment questionnaire (FAQ), and neuropsychiatric inventory.

RESULTS: MBI occurred in 53.5% aMCI and 19.6% CN. In aMCI, the most prevalent behaviors were affective dysregulation (34.4%), impulse dyscontrol (30.6%), and decreased drive/motivation (15.9%), whereas affective dysregulation (13.1%) and impulse dyscontrol (10.2%) were most prevalent in CN. In aMCI, affective dysregulation, decreased drive, social inappropriateness and abnormal perception MBI domains significantly predicted the FAQ score, whereas only decreased drive/motivation MBI domain showed a predicted role on FAQ in CN. No effects of MBI were detected on regional tau deposition or brain volumes in aMCI.

CONCLUSIONS: Our findings suggest that the occurrence of MBI might predict a high risk of dysfunction in daily life in both aMCI and CN. An early detection of functional impairment may improve the success of disease-modifying interventions.},
}

@article {pmid41076363,
year = {2025},
author = {Kong, J and So, M and Park, H and Kim, YT and Kim, H and Pahk, K and Kang, SH and Do, S and Lim, DK and Lee, CN and Kim, JB},
title = {Electroencephalography functional network for screening amyloid positivity in mild cognitive impairment: a cross-sectional study.},
journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology},
volume = {},
number = {},
pages = {2111374},
doi = {10.1016/j.clinph.2025.2111374},
pmid = {41076363},
issn = {1872-8952},
abstract = {OBJECTIVE: Monoclonal antibodies targeting amyloid-β (Aβ) show disease-modifying potential in Alzheimer's disease (AD), making early identification of Aβ-positive individuals at the mild cognitive impairment (MCI) stage essential. Functional network metrics derived from electroencephalography (EEG) may reflect Aβ-related network disruption and serve as viable screening tools.

METHODS: This study included patients with cognitive decline who underwent [18]F-flutemetamol PET/CT, EEG, and neuropsychological testing at Korea University Anam Hospital (2020-2024). Participants were categorized into subjective cognitive decline (SCD), MCI, or dementia. Resting-state EEG was analyzed using the weighted phase lag index to compute functional connectivity, followed by graph theoretical analysis to assess global network properties. Machine learning models were used to classify Aβ status in the MCI group based on EEG-derived features.

RESULTS: Among 100 participants (19 SCD, 55 MCI, 26 dementia), 53 were Aβ-positive. In MCI, Aβ-positive individuals (n = 28) showed significantly reduced delta-band network strength, global/local efficiency, clustering coefficient, and transitivity (all p < 0.05). Classification models reached an AUC of up to 0.850.

CONCLUSIONS: Resting-state EEG network analysis provides a non-invasive, cost-effective approach for screening Aβ positivity in MCI.

SIGNIFICANCE: EEG-based global network measures may aid in early AD diagnosis and patient selection for anti-Aβ therapies.},
}

@article {pmid41076120,
year = {2025},
author = {Guan, T and He, J and Zeng, L and Zhou, R and Chi, K and Yang, Y and Xiao, X and Pan, L and Liang, H and Luo, Z and Li, R and Wang, J and Gao, X and Tai, R and Chen, H and Ye, J and Ke, Y and Deng, Z and Wei, Q and Zhang, K and Ou, C},
title = {Rural-urban disparities in cardiovascular and other competing risk of death among cancer patients.},
journal = {Journal of advanced research},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jare.2025.10.011},
pmid = {41076120},
issn = {2090-1224},
abstract = {INTRODUCTION: Rural-urban disparity of cancer is a major public health problem, with an unclear gap in noncancer death. It is important to evaluate rural-urban disparities in cardiovascular diseases (CVDs) and other competing death among cancer patients.

OBJECTIVES: Observing urban-rural disparities and trends in noncancer deaths in the U.S. cancer population.

METHODS: To address rural-urban disparities, we used proportions of deaths, age-adjusted mortality rates (AAMR), cumulative mortality rates, subdistribution hazard ratio (sHR), standardized mortality ratios (SMRs), absolute excess risks (AERs) and mediation analysis.

RESULTS: Between 1990 and 2017, there were 2,022,482 patients of 24 cancer sites, with a median follow-up of 11·8 years. Rural proportions of noncancer and CVD deaths in cancer patients were higher than urban ones. Rural AAMR of noncancer and CVD deaths surpassed urban one in cancer patients, who had higher cumulative mortality rates than urban counterparts in noncancer (sHR:1·21, 95 % confidence interval [CI]:1·19-1·22), CVDs (sHR:1·25, 95 % CI: 1·23-1·28), diabetes mellitus (sHR:1·24, 95 % CI:1·15-1·34), Alzheimer's disease (sHR:1·30, 95 % CI:1·21-1·39), pneumonia and influenza (sHR:1·30, 95 % CI:1·21-1·39) and chronic obstructive pulmonary disease and allied cond (sHR:1·32, 95 % CI:1·26-1·39). Compared with the general population, both rural (SMR:4·58, AER:218·03) and urban (SMR: 3·74, AER: 166·61) cancer patients had higher risks of noncancer death. Mediation analyses identified median household income and SEER stages as the mediators.

CONCLUSION: Rural cancer patients had higher risks of noncancer death than urban counterparts, especially CVD-related deaths. Future targeted policy and public health interventions are needed to diminish the rural-urban gap in such death disparities.},
}

@article {pmid41076066,
year = {2025},
author = {Rolfsen, ML and Mart, MF and Kieffer, H and Krasinski, D and Girard, TD and Ferrante, LE and Owens, RL and Fuentes, AL and Brummel, N and Sevin, CM and Kress, JP and Singh, J and Nagi, S and Shaw, K and Qian, E and Jackson, JC and Hughes, CG and Pandharipande, P and Patel, M and Elasy, T and Ely, EW},
title = {Post Intensive Care Syndrome Awareness and Communication: Surveys of ICU Providers and Patients.},
journal = {Chest},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.chest.2025.08.048},
pmid = {41076066},
issn = {1931-3543},
abstract = {BACKGROUND: Survivors of critical illness often experience new or worsening impairments in various domains of health following discharge, collectively referred to as the Post Intensive Care Syndrome (PICS). While this condition is common, it remains unclear whether providers are routinely communicating about survivorship and PICS to patients and families, and whether patients are remembering these conversations.

RESEARCH QUESTION: How often do Intensive Care Unit (ICU) providers discuss the concept of PICS with at-risk patients or families, and how often do patients remember being told about the concept of PICS?

STUDY DESIGN AND METHODS: We distributed online surveys to ICU healthcare providers at nine U.S. institutions and to patients who survived critical illness in the preceding year at a single site.

RESULTS: We collected a convenience sample of 382 provider responses and 148 patient responses. The providers were registered nurses (53.7%), physician fellows or attendings (33%), and advanced practice providers (13.4%). Patients had predominantly been admitted to surgical (41.1%), cardiovascular (41.1%), and medical (14.4%) ICUs. We found that 73.8% of providers reported having previously heard the term "Post Intensive Care Syndrome." In comparison, only 16.6% of patients remembered ever being told the term. When asked how often they would discuss with patients or families the possibility of any new or worsening impairments following critical illness, less than a third (29.9%) of providers said they do so at least half the time. Only about a third (35.6%) of patients remembered such conversations.

INTERPRETATION: Awareness of PICS is inconsistent among providers and low among patients. Few ICU team members report routinely talking to patients or families about the common, disabling impairments that often occur following critical illness. Few patients remember being told about the possibility of PICS. Further investigation is needed to determine how best to improve this communication gap.},
}

@article {pmid41076002,
year = {2025},
author = {Pantiya, P and Chattipakorn, N and Chattipakorn, SC},
title = {Exploring the role of CD147 in cerebrovascular and Alzheimer's pathologies: Insights into mechanisms and interventions.},
journal = {Experimental neurology},
volume = {},
number = {},
pages = {115498},
doi = {10.1016/j.expneurol.2025.115498},
pmid = {41076002},
issn = {1090-2430},
abstract = {Cluster of Differentiation 147 (CD147), a multifunctional transmembrane glycoprotein, has been identified as a key regulator in the pathophysiology of cerebrovascular diseases and Alzheimer's disease (AD). In cerebrovascular conditions, CD147 contributes to neurological dysfunction by modulating pathways related to extracellular matrix remodeling, angiogenesis, and neuroinflammation. In AD, CD147 exhibits a complex, context-dependent role. Upregulation of CD147 has been implicated in increased amyloid-beta (Aβ) production and impaired energy metabolism, both of which contribute to cognitive decline. Paradoxically, other studies suggest that CD147 may exert neuroprotective effects by promoting Aβ degradation and preserving blood-brain barrier (BBB) integrity. These contradictory findings highlight the dualistic nature of CD147's functions, suggesting it may act as both a pathogenic and protective factor in AD. As evidence regarding its roles continues to grow, a more integrated understanding is needed to determine whether CD147 should be pursued as a viable biomarker or therapeutic target in cerebrovascular and neurodegenerative diseases. Therefore, this review aims to comprehensively synthesize current findings from clinical data, animal models, and in vitro studies to elucidate CD147's functions in cerebrovascular disease and AD. Additionally, we explore emerging therapeutic strategies targeting CD147-related pathways, which may offer promising avenues for neuroprotection.},
}

@article {pmid41075965,
year = {2025},
author = {Oppenheimer, H and Shadrin, A and Andersen, JØ and Schindler, LS and Crestol, A and Andreassen, OA and Westlye, LT and de Lange, AG and van der Meer, D and Barth, C},
title = {Investigating Shared Cardiovascular Factors and Genetic Overlap of Pregnancy-Related Disorders, Major Depressive Disorder, and Alzheimer's Disease.},
journal = {Biological psychiatry},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.biopsych.2025.09.018},
pmid = {41075965},
issn = {1873-2402},
abstract = {BACKGROUND: Pregnancy-related disorders, such as hypertensive disorders of pregnancy (HDP) and postpartum depression, have consequences for maternal health, increasing risk for major depressive disorder (MDD) and Alzheimer's disease (AD). Observational studies show intertwined pathophysiologies and shared cardiovascular factors. However, genetic links of cardiovascular factors with pregnancy-related disorders, MDD, and AD, as well as the genetic mechanisms between the disorders, have not been fully established.

METHODS: Using summary statistics from female-specific genome-wide association studies, we estimated genetic correlations and causal associations, using Mendelian randomization, between cardiovascular factors (C-reactive protein, HDL-cholesterol, LDL-cholesterol, and triglycerides), pregnancy-related disorders (HDP and postpartum depression), MDD, and AD. For significant associations, BMI, as a known confounder, was included in multivariable Mendelian randomization analyses. Further, we applied causal mixture models (MiXeR) to explore polygenic overlap between pregnancy-related disorders, MDD, and BMI.

RESULTS: We found widespread genetic correlations between cardiovascular factors, pregnancy-related disorders, and MDD. Using Mendelian randomization, higher triglycerides and lower HDL-cholesterol were causally linked to higher HDP risk, and higher LDL-cholesterol to higher AD risk. When including BMI, only the effect of triglycerides on HDP remained significant. Trivariate MiXeR estimated substantial polygenic overlap of pregnancy-related disorders with MDD and BMI.

CONCLUSIONS: Using multiple genetic approaches, our findings indicate some shared cardiovascular factors associated with pregnancy-related disorders, MDD, and AD, partly driven by BMI. BMI should be further explored as a modifiable factor genetically linked to pregnancy-related, mental, and brain disorders. Our findings highlight the relevance of early prevention of genetically interconnected disorders across the female lifespan.},
}

@article {pmid41075952,
year = {2025},
author = {Li, D and Xue, A and Guan, Y and Qiu, Q and Ren, Y and Zhang, N},
title = {Investigation of Kai-Xin-San in alleviating cognitive impairment in aβ transgenic Caenorhabditis elegans through mitochondrial function regulation.},
journal = {Fitoterapia},
volume = {},
number = {},
pages = {106921},
doi = {10.1016/j.fitote.2025.106921},
pmid = {41075952},
issn = {1873-6971},
abstract = {Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline, mitochondrial dysfunction, and amyloid β-protein (Aβ) accumulation, with limited safe and effective treatments available. Kai-Xin-San (KXS), a traditional Chinese medicine formula (Panax ginseng, Poria cocos, Polygala tenuifolia, Acorus calamus), has shown potential in alleviating AD symptoms, but its mechanisms, especially mitochondrial regulation-related ones, remain unclear. Using Aβ-overexpressing Caenorhabditis elegans (Aβ-C. elegans) as an AD model, this study evaluated KXS's pharmacodynamic effects via serotonin sensitivity and chemotaxis assays, identified its absorbed components via UPLC-Q/TOF-MS, predicted anti-AD mechanisms via bioinformatics (GO/KEGG) and metabolomics, and assessed mitochondrial function via ROS, ATP, SOD, MDA, JC-1 assays, as well as RT-qPCR/Western blotting of mitochondrial pathways. Results showed that 10 mg/mL KXS significantly reduced Aβ-C. elegans paralysis by 27.1 % (P < 0.01) and improved associative learning (P < 0.01); 20 KXS components were characterized in vivo, and KXS reduced ROS/MDA, elevated ATP/SOD (P < 0.01), restored mitochondrial membrane potential, regulated mitochondrial biogenesis/autophagy (hmg-5, bec-1, lgg-1) and fission genes (drp-1, fis-1), and activated the AMPK/SIRT1 pathway (aak-1, sir-2.1, SIRT1/p-AMPK), thereby improving cognitive impairment in Aβ-C. elegans. This finding clarifies its neuroprotective mechanism and provides evidence for its potential as a therapeutic candidate for AD.},
}

@article {pmid41075879,
year = {2025},
author = {Kučinskas, G and Kozeleková, A and Králová, K and Volko, V and Šedo, O and Hritz, J},
title = {14-3-3ζ protein prevents formation of GSK3β-phosphorylated Tau protein fibrils.},
journal = {International journal of biological macromolecules},
volume = {},
number = {},
pages = {148222},
doi = {10.1016/j.ijbiomac.2025.148222},
pmid = {41075879},
issn = {1879-0003},
abstract = {Alzheimer's Disease remains one of the challenges in modern-day medicine, lacking any blockbuster therapy. Despite understanding the pathology and identifying neurofibrillary tangles as a hallmark of the disease, the molecular mechanisms behind it still remain unclear. Understanding post-translational modifications (PTMs) and 14-3-3 protein role can be crucial in uncovering tauopathies progression. Our study was focused on the phosphorylation of recombinant full-length Tau by Glycogen synthase kinase-3 beta (GSK3β). We targeted phosphorylation, particularly at the C terminus and residues identified as AD phospho-biomarkers. Additionally, our study investigated the effect of 14-3-3ζ (highly abundant in the human brain) on the fibrillisation of Tau phosphorylated by GSK3β. Using our optimised fibrillisation conditions, we compared Tau fibril formation both in the presence and absence of 14-3-3ζ protein. Notably, 14-3-3ζ protein significantly inhibited fibril formation under these conditions. This conclusion was supported by both quantitative measurements using the Thioflavin T (ThT) assay and qualitative assessments through visualisation techniques, including negative-stain electron microscopy (NS-EM) and atomic force microscopy (AFM). Besides, chemical cross-linking and nuclear magnetic resonance spectroscopy (NMR) revealed direct interaction between 14 and 3-3ζ and GSK3β-phosphorylated Tau, proposing the molecular mechanism of inhibition. These findings suggest that 14-3-3ζ may exert a protective role in Alzheimer's Disease by modulating Tau aggregation.},
}

@article {pmid41075819,
year = {2025},
author = {Sinvani, L and Izard, S and Perrin, A and Liu, Y and Chiuzan, C and Slotnick, S and Affoo, R and Rogus-Pulia, N and Makhnevich, A},
title = {Nil per os on Admission and Dehydration Are Risk Factors for Delirium in Hospitalized Older Adults With Dementia and Dysphagia.},
journal = {Journal of the American Medical Directors Association},
volume = {},
number = {},
pages = {105912},
doi = {10.1016/j.jamda.2025.105912},
pmid = {41075819},
issn = {1538-9375},
abstract = {OBJECTIVES: Patients with Alzheimer's disease and related dementias (ADRD) experience oral intake restriction. The objective of this study was to determine whether nil per os (NPO) and dysphagia diets (thickened liquids) are associated with delirium in patients with ADRD and whether dehydration mediates these relationships.

DESIGN: Retrospective cohort study.

SETTING AND PARTICIPANTS: Data were obtained from a large integrated health system in New York (11 hospitals) and included hospitalized older adults (aged ≥65 years) with ADRD admitted between 2017 and 2022 with clinical suspicion of dysphagia.

METHODS: The main variables were NPO on admission (≥24 vs <24 hours; cohort 1) and prescription of thickened liquids (vs thin liquids; cohort 2). The primary outcome was new delirium developed 48 hours after admission. Multivariable logistic regression was used to determine the association between NPO time and new delirium while adjusting for all prespecified covariates of interest. The relationship between thickened liquids and new delirium was assessed similarly to NPO time.

RESULTS: Of 11,933 patients, the average age ± SD was 85.8 ± 7.92 years. In a multivariable model of cohort 1, NPO (odds ratio [OR], 1.398; 95% CI, 1.273-1.536; P < .001) and dehydration (OR, 1.837; 95% CI, 1.678-2.012; P < .001) were associated with higher odds of new delirium. In a multivariable model of cohort 2, thickened liquids were associated with decreased odds of new delirium (OR 0.867; 95% CI: 0.796, 0.945; P = .001), whereas NPO (OR, 1.480; 95% CI, 1.340-1.634; P < .001) and dehydration (OR, 1.804; 95% CI, 1.634-1.991; P < .001) were associated with increased odds of new delirium. Dehydration did not mediate the relationship between restriction and new delirium.

CONCLUSIONS AND IMPLICATIONS: Limiting NPO and preventing dehydration could lower delirium risk and improve outcomes for patients with ADRD. Future research is needed to confirm these results.},
}

@article {pmid41075815,
year = {2025},
author = {Wu, JY and Lin, YM and Hsu, WH and Liu, TH and Tsai, YW and Huang, PY and Chuang, MH and Yu, T and Lai, CC},
title = {Glucagon-Like Peptide-1 Receptor Agonists and Dementia Risk Reduction in Older Adults With Type 2 Diabetes: A Retrospective Cohort Study.},
journal = {Journal of the American Medical Directors Association},
volume = {},
number = {},
pages = {105901},
doi = {10.1016/j.jamda.2025.105901},
pmid = {41075815},
issn = {1538-9375},
abstract = {OBJECTIVE: To evaluate the effect of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on dementia risk compared with dipeptidyl peptidase-4 inhibitors (DPP-4is) among older adults with type 2 diabetes (T2D).

DESIGN: Retrospective cohort study using an active-comparator, new-user design with propensity score matching.

SETTING AND PARTICIPANTS: Data were obtained from the TriNetX Global Collaborative Network, which includes electronic health records from 134 health care organizations worldwide. Participants were adults aged ≥65 years with T2D who initiated GLP-1RA or DPP-4i therapy between January 2017 and November 2024.

METHODS: Eligible participants were matched 1:1 on baseline characteristics using propensity score matching (PSM). The primary outcome was incident dementia. Secondary outcomes included prescriptions for dementia-related drugs, Alzheimer's disease, and vascular dementia. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazards models, and subgroup and sensitivity analyses were performed.

RESULTS: After PSM, 82,689 patients were included in each treatment group. GLP-1RA use was associated with a lower risk of dementia compared with DPP-4i (HR, 0.58; 95% CI, 0.55-0.61; P < .0001). Stratified analyses revealed consistent risk reductions across age, sex, and GLP-1RA type. In addition, GLP-1RA was also associated with lower risks of dementia-related drug prescriptions (HR, 0.76; 95% CI, 0.70-0.81), Alzheimer's disease (HR, 0.62; 95% CI, 0.56-0.70), and vascular dementia (HR, 0.62; 95% CI, 0.55-0.70). Sensitivity analyses supported the robustness of these findings.

CONCLUSIONS AND IMPLICATIONS: GLP-1RA use in older adults with T2D is associated with a significantly lower risk of dementia compared with DPP-4i. These findings suggest the potential neuroprotective benefits of GLP-1RAs and highlight their importance in managing T2D with a view toward reducing dementia risk. Further studies are warranted to explore the underlying mechanisms and validate these observations in randomized controlled trials.},
}

@article {pmid41075678,
year = {2025},
author = {Del Puerto, JMAR and Matias-Guiu, JA},
title = {Functional cognitive disorders and Alzheimer's disease: Friend or foe?.},
journal = {Journal of the neurological sciences},
volume = {478},
number = {},
pages = {123711},
doi = {10.1016/j.jns.2025.123711},
pmid = {41075678},
issn = {1878-5883},
}

@article {pmid41075540,
year = {2025},
author = {Zhou, J and Huang, N and Huang, T and Ma, J},
title = {Investigating the longitudinal relationship between Vitamin D levels, sleep duration, and dementia risk: insights from the UK Biobank.},
journal = {Psychiatry research},
volume = {353},
number = {},
pages = {116759},
doi = {10.1016/j.psychres.2025.116759},
pmid = {41075540},
issn = {1872-7123},
abstract = {BACKGROUND: Dementia, particularly Alzheimer's disease (AD) and vascular dementia (VD), presents a growing global burden. Modifiable risk factors, including vitamin D levels and sleep duration, have been implicated, but their associations with dementia risk remain unclear.

METHODS: We analyzed data from the UK Biobank, a prospective cohort of over 500,000 individuals aged 40-69 years. Serum 25-hydroxyvitamin D [25(OH)D] levels and self-reported sleep duration were categorized into three groups each: <25, ≥25 to <50, and ≥50 nmol/L for vitamin D; <6, ≥6 to <9, and ≥9 h for sleep. Cox proportional hazards models were used to examine the independent and joint effects of vitamin D and sleep duration on incident dementia, adjusting for demographic, lifestyle, and medical confounders.

RESULTS: A significant interaction between low vitamin D levels and abnormal sleep duration was observed. Individuals with 25(OH)D < 25 nmol/L and either short (<6 h) or long (≥9 h) sleep had the highest risk for all-cause dementia, AD, and VD. However, low vitamin D alone was not independently associated with dementia over 20 years of follow-up.

CONCLUSIONS: This study identifies a synergistic effect between vitamin D deficiency and atypical sleep duration on dementia risk. Addressing both factors may enhance prevention strategies. These findings support the need for further trials to evaluate causal relationships and intervention efficacy.},
}

@article {pmid41075395,
year = {2025},
author = {De Simone, MS and Bonarota, S and Serra, L and Rodini, M and Caruso, G and Giove, F and Caltagirone, C and Carlesimo, GA},
title = {Long-term associative memory and spatial pattern separation impairments in individuals with subjective cognitive decline: A neuropsychological and medial temporal lobe subregions volumetric analysis.},
journal = {Cortex; a journal devoted to the study of the nervous system and behavior},
volume = {192},
number = {},
pages = {196-212},
doi = {10.1016/j.cortex.2025.09.009},
pmid = {41075395},
issn = {1973-8102},
abstract = {Subjective cognitive decline (SCD) has been proposed as a potential preclinical stage of Alzheimer's disease (AD) dementia. This study aimed to investigate whether objective impairments could be identified in SCD on highly demanding memory tasks and their possible associations with medial temporal lobe (MTL) volumes. The performance of 31 individuals with SCD and 29 healthy elderly with no worries of cognitive decline (HC) was compared on two experimental tasks assessing respectively face-name-occupation associative memory and spatial pattern separation. The diagnostic power of these tests in classifying cognitive status was assessed. In addition, a sub-group of 20 SCD and 19 HC underwent a 3T-MRI. Volumes of individual hippocampal subfields and surrounding cortices within the MTL were calculated and compared between the two groups. Finally, possible associations between brain volumes and performance on experimental tasks were evaluated. While traditional neuropsychological tests showed no significant between-group differences, SCDs obtained significantly lower scores than HCs on experimental tasks. These measures also correctly classified group membership with good overall accuracy. Volumetric data revealed significant between-group differences in specific hippocampal subfields (particularly CA1 and dentate gyrus) and surrounding cortices (particularly entorhinal and perirhinal cortices). Furthermore, lower scores on experimental tasks significantly correlated with reduced volumes in specific MTL sub-regions (particularly CA1 and perirhinal cortices). These findings provide the first evidence in SCD of an association between objective memory impairments in associative memory and spatial pattern separation and volume reductions in specific MTL sub-regions known to be primarily vulnerable to AD neuropathology.},
}

@article {pmid41075250,
year = {2025},
author = {Houmam, S and Siodlak, D and Pham, KD and Salinas-Salinas, C and Ocañas, SR and Freeman, WM and Rice, HC},
title = {Protocol to sequentially isolate mouse oligodendrocytes, microglia, endothelial cells, astrocytes, and neurons via magnetic cell sorting.},
journal = {STAR protocols},
volume = {6},
number = {4},
pages = {104139},
doi = {10.1016/j.xpro.2025.104139},
pmid = {41075250},
issn = {2666-1667},
abstract = {Isolation of specific brain cell types is essential to study cell-type-specific differences in complex neurological diseases such as Alzheimer's disease. Here, we present a protocol for isolating oligodendrocytes, microglia, endothelial cells, astrocytes, and neurons from a single mouse brain. We describe steps for tissue homogenization, debris removal, and sequential sorting. We then detail procedures for validating cell purity and viability using flow cytometry and quantitative reverse-transcription PCR (RT-qPCR). This protocol is well suited for a range of downstream applications, including genomics, transcriptomics, and proteomics.},
}

@article {pmid41078896,
year = {2025},
author = {Guo, X and Gao, F and Pan, B and Gao, F and Zhang, J and Wang, S and Niu, Q},
title = {Causal association of plasminogen activators and their inhibitors with Alzheimer's disease: a Mendelian randomization study.},
journal = {Archives of medical science : AMS},
volume = {21},
number = {4},
pages = {1323-1331},
pmid = {41078896},
issn = {1734-1922},
abstract = {INTRODUCTION: Alzheimer's disease (AD) is the most common cause of dementia and contributes to a huge burden of disease worldwide. Observational studies have found that tissue plasminogen activator (t-PA) inhibits the development of AD, but little is known about urokinase plasminogen activator (u-PA) or plasminogen activator inhibitor-1 (PAI-1). At present, the causal relationship is not clear. Therefore, this study intended to explore the relationship between plasminogen activators and their inhibitors with Alzheimer's disease through the Mendelian randomization method, so as to provide a reference for the prevention and control of Alzheimer's disease.

MATERIAL AND METHODS: To investigate causal pathways, we conducted a two-sample Mendelian randomization study using pooled statistics from genome-wide association studies. Inverse-variance weighted (IVW), Mendelian randomization-Egger (MR-Egger), weighted-median, Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) and Mendelian randomization-robust adjusted profile score (MR-RAPS) methods were used to evaluate the robustness of the results.

RESULTS: In the outcome of AD (more controls excluded), the IVW effect of PAI-1 OR (95% CI) was found as follows: 1.543 (1.010-2.356), whose interval does not include 1 and p = 0.0448, which suggested that PAI-1 was positively correlated with the risk of AD (more controls excluded). The IVW model, weighted median, MR-PRESSO and MR-RAPS all showed similar results (all odds ratios [ORs] > 1), and the two outcomes were consistent.

CONCLUSIONS: Our results showed that gene-predicted PAI-1 in Mendelian stochastic analysis was associated with an increased risk of AD.},
}

@article {pmid41075221,
year = {2025},
author = {Kucharczyk, P and Szczepanik, K and Parzęcka, K and Żerańska, A and Michalak, M and Kusy, B and Domaradzki, O and Bieńkowski, W and Charkot, J},
title = {Exploring the Neurological Impacts of the Ketogenic Diet: A Comprehensive Review.},
journal = {Wiadomosci lekarskie (Warsaw, Poland : 1960)},
volume = {78},
number = {8},
pages = {1664-1669},
doi = {10.36740/WLek/208442},
pmid = {41075221},
issn = {0043-5147},
mesh = {*Diet, Ketogenic ; Humans ; *Nervous System Diseases/diet therapy ; },
abstract = {OBJECTIVE: Aim: This review aims to conduct an analysis of potential therapeutic effects, mechanisms of action, and consequences of the ketogenic diet in the context of the mentioned neurological disorders.

PATIENTS AND METHODS: Materials and Methods: A review of scientific literature available in the PubMed and Google Scholar databases was conducted, utilizing key terms.

CONCLUSION: Conclusions: The presented work provides an integrated compilation of currently available studies analyzing the impact of the ketogenic diet and underscores the importance of continuing research to achieve a fuller understanding of the mechanisms of action of this diet and its potential therapeutic benefits.},
}

*Diet, Ketogenic
Humans
*Nervous System Diseases/diet therapy

@article {pmid41075024,
year = {2025},
author = {Abedimanesh, N and Miri, SA and Mohammadi, A and Shahmohammadi, F and Danafar, H and Eskandari, MR and Hejazi, S and Andalib, S and Motlagh, B},
title = {Protective and therapeutic effects of betanin nanoparticles in an alzheimer's rat model: modulation of behavior and expression of AQP4, BDNF, SIRT6, and Seladin-1.},
journal = {Metabolic brain disease},
volume = {40},
number = {7},
pages = {286},
pmid = {41075024},
issn = {1573-7365},
support = {A-12-898-19//The Vice Chancellor for Research of Zanjan University of Medical Sciences, Zanjan, Iran/ ; },
mesh = {Animals ; *Brain-Derived Neurotrophic Factor/genetics/metabolism/biosynthesis ; *Alzheimer Disease/drug therapy/metabolism ; Rats ; *Nanoparticles/administration & dosage ; *Sirtuins/genetics/biosynthesis/metabolism ; *Neuroprotective Agents/administration & dosage/pharmacology/therapeutic use ; Male ; *Aquaporin 4/genetics/biosynthesis/metabolism ; *Betacyanins/administration & dosage/therapeutic use/pharmacology ; *Nerve Tissue Proteins/biosynthesis/genetics/metabolism ; Disease Models, Animal ; Hippocampus/metabolism/drug effects ; Microfilament Proteins/biosynthesis/genetics/metabolism ; Antioxidants ; Behavior, Animal/drug effects ; Maze Learning/drug effects ; },
abstract = {Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive decline, oxidative stress, and neuroinflammation. Betanin, a natural antioxidant, has shown neuroprotective potential, but its clinical use is limited by poor bioavailability. This study investigates the effects of betanin-loaded nanomicelles, designed to enhance brain delivery, in a scopolamine-induced rat model of AD. Nanomicelles were synthesized and characterized using TEM, DLS, and FT-IR. Rats received either pre- or post-treatment with betanin nanomicelles, free betanin, donepezil, or saline. Cognitive performance was assessed using the Morris Water Maze. Gene expression levels of AQP4, BDNF, SIRT6, and Seladin-1 were measured using real-time PCR, and antioxidant activity was evaluated by assessing glutathione (GSH) and glutathione reductase (GR) in hippocampal tissue. Betanin nanomicelles improved spatial memory, increased BDNF and SIRT6 expression, and reduced AQP4 levels, indicating potential neuroprotection. Seladin-1 expression was notably elevated in the pre-treatment group, suggesting support for neuronal survival. Antioxidant assays showed restoration of GSH and GR activity. These findings suggest that betanin nanomicelles may enhance cognitive function and modulate neuroprotective pathways more effectively than free betanin, supporting their potential as a novel therapeutic strategy for AD.},
}

Animals
*Brain-Derived Neurotrophic Factor/genetics/metabolism/biosynthesis
*Alzheimer Disease/drug therapy/metabolism
Rats
*Nanoparticles/administration & dosage
*Sirtuins/genetics/biosynthesis/metabolism
*Neuroprotective Agents/administration & dosage/pharmacology/therapeutic use
Male
*Aquaporin 4/genetics/biosynthesis/metabolism
*Betacyanins/administration & dosage/therapeutic use/pharmacology
*Nerve Tissue Proteins/biosynthesis/genetics/metabolism
Disease Models, Animal
Hippocampus/metabolism/drug effects
Microfilament Proteins/biosynthesis/genetics/metabolism
Antioxidants
Behavior, Animal/drug effects
Maze Learning/drug effects

@article {pmid41074965,
year = {2025},
author = {Liu, Y and Zhong, R and Wu, X and Zhang, J and Kou, Z},
title = {Global hotspots and trends in AMPA receptor research (2000-2025): a bibliometric and visualization analysis.},
journal = {Naunyn-Schmiedeberg's archives of pharmacology},
volume = {},
number = {},
pages = {},
pmid = {41074965},
issn = {1432-1912},
abstract = {AMPA receptors (AMPARs) are critical excitatory ionotropic glutamate receptors involved in synaptic transmission, plasticity, and various neurological disorders. From 2000 to present (up to 2025), extensive research has explored their roles in brain function and disease, yet a comprehensive bibliometric analysis of this field is lacking. This study aims to provide a systematic bibliometric overview of AMPAR research from 2000 to present, identifying key trends, influential contributors, and emerging hotspots to guide future investigations. Data were retrieved from Web of Science, PubMed, and Scopus, encompassing 37,000 distinct publications. Bibliometric tools (CiteSpace, VOSviewer, and Bibliometrix) were employed to analyze publication trends, country/institution contributions, journal metrics, author productivity, and keyword clusters. The United States led in publication output (6,142 articles) and citations (410,626), followed by China and Japan. The Journal of Neuroscience and Neuron were the top journals, while Huganir RL was the most cited author. Research hotspots evolved from fundamental AMPAR properties (e.g., subunit composition) to disease associations (e.g., Alzheimer's, depression) and therapeutic strategies (e.g., AMPAR modulators). Keyword analysis revealed four themes: biochemical properties, physiological functions, pathological roles, and therapeutic targets. AMPAR research has transitioned from basic neurophysiology to translational applications, with growing emphasis on neurological and psychiatric disorders. Future directions include elucidating native AMPAR complexes, trafficking dynamics, and precision therapeutics. This study highlights the field's progression and underscores the need for interdisciplinary collaboration to address unresolved challenges.},
}

@article {pmid41074918,
year = {2025},
author = {Al-Amin, MM and Kim, B and Karahan, H and Tate, MD and Walsh, SP and Puntambekar, SS and Bissel, SJ and Lamb, BT and Wang, N and Kim, J},
title = {Apolipoprotein ε4 exacerbates white matter impairment in a mouse model of Aβ amyloidosis by decreasing actively myelinating oligodendrocytes.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21},
number = {10},
pages = {e70791},
pmid = {41074918},
issn = {1552-5279},
support = {//Indiana University/ ; //Strategic Research Initiative fund/ ; //Precision Health Initiative fund/ ; R01AG077829/NH/NIH HHS/United States ; R01AG071281/NH/NIH HHS/United States ; R21AG072738/NH/NIH HHS/United States ; RF1AG074543/NH/NIH HHS/United States ; 5T32AG071444//National Institute of Aging, Alzheimer's Disease & ADRD/ ; AARF-21-852175//Alzheimer's Association Fellowship/ ; F31AG074673/AG/NIA NIH HHS/United States ; },
mesh = {Animals ; *Oligodendroglia/pathology/metabolism ; *Apolipoprotein E4/genetics/metabolism ; Disease Models, Animal ; *White Matter/pathology/diagnostic imaging/metabolism ; Mice, Transgenic ; Mice ; *Amyloidosis/pathology/genetics/diagnostic imaging/metabolism ; *Amyloid beta-Peptides/metabolism ; *Myelin Sheath/pathology/metabolism ; Magnetic Resonance Imaging ; Humans ; Apolipoprotein E3/genetics/metabolism ; Neurites/pathology ; Brain/pathology/diagnostic imaging ; Corpus Callosum/pathology/diagnostic imaging ; },
abstract = {INTRODUCTION: The ε4 allele of the apolipoprotein E (APOE) gene is a risk factor for the development of Alzheimer's disease (AD). APOE4 isoform is associated with increased white matter lesions in humans. To identify the underlying mechanisms of white matter impairment associated with APOE4, we investigated the effects of APOE4 and APOE3 on multiple readouts of the white matter microstructural integrity.

METHODS: Using magnetic resonance imaging and immunohistochemistry approaches, we analyzed white matter tracts in 5xFAD mice expressing APOE3 (5xFAD;APOE3) or APOE4 (5xFAD;APOE4).

RESULTS: APOE4 significantly decreased fractional anisotropy, axial diffusivity, and neurite density index, while increasing radial diffusivity and isotropic volume fraction within major white matter tracts. Myelination was reduced in the corpus callosum of 5xFAD;APOE4 mice. Mechanistically, APOE4 reduced populations of mature and actively myelinating oligodendrocytes.

DISCUSSION: Our results suggest that a decrease in the number of actively myelinating oligodendrocytes may explain myelin loss, leading to white matter impairments.

HIGHLIGHTS: A robust neurite orientation dispersion and density imaging (NODDI) approach to study the effect of apolipoprotein E (APOE) isoforms on the white matter in 5xFAD mice. APOE4 reduces neurite density and increases water accumulation in the white matter. APOE4 disrupts structural connectivity and reduces the betweenness centrality. APOE4 decreases the number of actively myelinating oligodendrocytes. A reduction in myelinating oligodendrocyte populations may lead to myelin loss.},
}

Animals
*Oligodendroglia/pathology/metabolism
*Apolipoprotein E4/genetics/metabolism
Disease Models, Animal
*White Matter/pathology/diagnostic imaging/metabolism
Mice, Transgenic
Mice
*Amyloidosis/pathology/genetics/diagnostic imaging/metabolism
*Amyloid beta-Peptides/metabolism
*Myelin Sheath/pathology/metabolism
Magnetic Resonance Imaging
Humans
Apolipoprotein E3/genetics/metabolism
Neurites/pathology
Brain/pathology/diagnostic imaging
Corpus Callosum/pathology/diagnostic imaging

@article {pmid41074913,
year = {2025},
author = {Jacobs, T and Brien, CO and Figueredo, L and Gogola, A and Gaggi, NL and Hurwitz, B and Pirraglia, E and Herzog, S and Ramos-Cejudo, J and Shepherd, TM and Palta, P and Fortea, J and Wisniewski, TM and Betensky, RA and Lopresti, B and Mielke, MM and Convit, A and Osorio, RS and , },
title = {Body mass index and blood volume influence plasma biomarkers and positron emission tomography classification in preclinical Alzheimer's disease.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21},
number = {10},
pages = {e70765},
pmid = {41074913},
issn = {1552-5279},
support = {W81XWH-12-2-0012//U.S. Department of Defense/ ; U01AG024904/NH/NIH HHS/United States ; R01AG056031/NH/NIH HHS/United States ; R01AG056531/NH/NIH HHS/United States ; R01AG056682/NH/NIH HHS/United States ; R01AG068248/NH/NIH HHS/United States ; R01AG070821/NH/NIH HHS/United States ; R01AG079282/NH/NIH HHS/United States ; R01AG080609/NH/NIH HHS/United States ; R01AG055624/NH/NIH HHS/United States ; R01AG056850/NH/NIH HHS/United States ; R21AG056974/NH/NIH HHS/United States ; R01AG061566/NH/NIH HHS/United States ; R01AG081394/NH/NIH HHS/United States ; R61AG066543/NH/NIH HHS/United States ; AG080769-01/NH/NIH HHS/United States ; U24AG082930/NH/NIH HHS/United States ; P30AG066468/NH/NIH HHS/United States ; P01AG025204/NH/NIH HHS/United States ; P30AG066512/NH/NIH HHS/United States ; //Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas/ ; INT21/00073//Instituto de Salud Carlos III/ ; PI20/01473//Instituto de Salud Carlos III/ ; PI23/01786//Instituto de Salud Carlos III/ ; //Department de Salut de la Generalitat de Catalunya/ ; IIBSP-DOW-2020-151//Fundación Tatiana Pérez de Guzmán el Bueno/ ; H2020-SC1-BHC-2018-2020//Horizon 2020 Framework Programme/ ; //BrightFocus Foundation/ ; //Life Molecular Imaging/ ; },
mesh = {Humans ; *Alzheimer Disease/blood/diagnostic imaging/classification/diagnosis ; *Positron-Emission Tomography ; Male ; Female ; *Body Mass Index ; *Biomarkers/blood ; Aged ; *Blood Volume/physiology ; Amyloid beta-Peptides/blood ; tau Proteins/blood ; Aged, 80 and over ; Brain/diagnostic imaging ; },
abstract = {INTRODUCTION: Blood-based biomarkers (BBMs) are promising tools for Alzheimer's disease (AD) diagnosis, but their accuracy may be affected by body mass index (BMI) and blood volume (BV) through dilution. We investigated how BMI and BV influence BBM concentrations and PET prediction.

METHODS: Data from 241 cognitively unimpaired participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) were examined to evaluate the influence of BMI/BV on BBMs (Aβ42/40, p-Tau181, p-Tau217, glial fibrillary acidic protein [GFAP], neurofilament light chain [NfL]) and BBM-based PET predictions.

RESULTS: Elevated BMI/BV associated with lower BBM concentrations, especially for p-Tau217 and NfL, independent of brain amyloid burden. BMI-stratified thresholds improved amyloid PET prediction, with higher BBM thresholds and area under the curve (AUC) values seen in normal weight compared to overweight or obese participants. Drastic BMI/BV declines due to weight loss increased BBM variability and systematic PET misclassification.

DISCUSSION: Adjusting for BMI/BV in BBM-based diagnostics appears to improve accuracy and reliable detection of AD pathology, especially in preclinical stages.

HIGHLIGHTS: Body mass index (BMI) and blood volume (BV) significantly influenced plasma BBM concentrations in cognitively unimpaired (CU) individuals. Blood-based biomarkers (BBMs) associated more strongly with BV than with BMI. Dilution effects were independent of brain amyloid burden. BMI-stratified BBM thresholds improved amyloid positron emission tomography (PET) classification accuracy. Declines in BMI/BV resulted in PET prediction bias and systematic errors.},
}

Humans
*Alzheimer Disease/blood/diagnostic imaging/classification/diagnosis
*Positron-Emission Tomography
Male
Female
*Body Mass Index
*Biomarkers/blood
Aged
*Blood Volume/physiology
Amyloid beta-Peptides/blood
tau Proteins/blood
Aged, 80 and over
Brain/diagnostic imaging

@article {pmid41074912,
year = {2025},
author = {Ye, R and Goodheart, AE and Locascio, JJ and Peterec, EC and Stancu, P and Wang, Y and Gomperts, SN},
title = {APOE ε4 linked effects on clinical features and neuropathology in dementia with Lewy bodies.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21},
number = {10},
pages = {e70795},
pmid = {41074912},
issn = {1552-5279},
support = {R21NS109833/NS/NINDS NIH HHS/United States ; U01AG016976/NS/NINDS NIH HHS/United States ; P30AG062421/AG/NIA NIH HHS/United States ; //Michael J. Fox Foundation for Parkinson's Research/ ; W81XW1810516//Department of Defense CDMRP/ ; },
mesh = {Humans ; *Lewy Body Disease/genetics/pathology ; *Apolipoprotein E4/genetics ; Male ; Female ; Aged ; Hallucinations/genetics/pathology ; Alzheimer Disease/pathology/genetics ; Aged, 80 and over ; *Brain/pathology ; Lewy Bodies/pathology ; },
abstract = {INTRODUCTION: Apolipoprotein E (APOE) ε4 is a strong genetic risk factor for Alzheimer's disease (AD) neuropathologic changes, but its contribution to clinical features and pathology in dementia with Lewy bodies (DLB) is less clear.

METHODS: Using the National Alzheimer Coordinating Center dataset, we investigated APOE ε4-associated effects on DLB core clinical features and neuropathology.

RESULTS: In analyses of APOE ε4 carriers, dosage, and genetic risk score, APOE ε4 was associated with lower odds of fluctuating cognition and parkinsonism and higher odds of visual hallucinations. APOE ε4 was associated with greater neocortical Lewy body pathology, partially mediated by AD co-pathology. The severity of fluctuating cognition was associated with Lewy body pathology stage after controlling for AD co-pathology. Visual hallucinations were associated with both Lewy body and AD pathologies.

DISCUSSION: Core clinical features of DLB are sensitive to APOE haplotype. Targeting APOE biology may elucidate DLB pathogenesis and inform therapeutic development.

HIGHLIGHTS: Core clinical features of dementia with Lewy bodies were sensitive to apolipoprotein E (APOE) haplotype. APOE ε4 was associated with a higher likelihood of hallucinations yet a lower likelihood of cognitive fluctuations. APOE ε4 was associated with greater severity of Lewy body pathology, partially mediated by Alzheimer's disease (AD) co-pathology. Whereas fluctuating cognition was primarily linked to Lewy body pathology, visual hallucinations were associated with both Lewy body and AD neuropathologic changes.},
}

Humans
*Lewy Body Disease/genetics/pathology
*Apolipoprotein E4/genetics
Male
Female
Aged
Hallucinations/genetics/pathology
Alzheimer Disease/pathology/genetics
Aged, 80 and over
*Brain/pathology
Lewy Bodies/pathology

@article {pmid41074907,
year = {2025},
author = {Luo, W and Minhas, DS and Rubenstein, ED and Situ, DN and Royse, SK and Ances, BM and Christian, BT and Cohen, AD and Handen, BL and Klunk, WE and Tudorascu, DL and Zaman, S and Laymon, CM and , },
title = {Development and evaluation of image preprocessing pipelines for the Centiloid method on Down Syndrome data.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21},
number = {10},
pages = {e70712},
doi = {10.1002/alz.70712},
pmid = {41074907},
issn = {1552-5279},
support = {U01 AG051406/AG/NIA NIH HHS/United States ; U01 AG051412/AG/NIA NIH HHS/United States ; U19 AG068054/AG/NIA NIH HHS/United States ; //Investigation of Co-occurring conditions across the Lifespan to Understand Down Syndrome/ ; P50 AG008702/AG/NIA NIH HHS/United States ; P30 AG062421/AG/NIA NIH HHS/United States ; P50 AG16537//Alzheimer's Disease Research Centers Program/ ; P50 AG005133/AG/NIA NIH HHS/United States ; P50 AG005681/AG/NIA NIH HHS/United States ; P30 AG062715/AG/NIA NIH HHS/United States ; P30 AG066519/AG/NIA NIH HHS/United States ; P30 AG066468/AG/NIA NIH HHS/United States ; P30 AG072973/AG/NIA NIH HHS/United States ; P50 HD105353/HD/NICHD NIH HHS/United States ; UL1 TR001873/TR/NCATS NIH HHS/United States ; UL1 TR002373/TR/NCATS NIH HHS/United States ; UL1 TR001414/TR/NCATS NIH HHS/United States ; UL1 TR001857/TR/NCATS NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; UL1 TR002366/TR/NCATS NIH HHS/United States ; U24 AG21886//National Centralized Repository for Alzheimer Disease and Related Dementias/ ; //DS-Connect/ ; /AG/NIA NIH HHS/United States ; NIHR203312//National Institute for Health and Care Research (NIHR) Cambridge Biomedical Research Centre/ ; //NIHR Applied Research Collaboration East of England/ ; },
mesh = {Humans ; *Down Syndrome/diagnostic imaging ; *Magnetic Resonance Imaging/methods ; Positron-Emission Tomography/methods ; *Image Processing, Computer-Assisted/methods ; *Brain/diagnostic imaging/metabolism ; Male ; Female ; Middle Aged ; },
abstract = {BACKGROUND: Centiloid provides a standardized process to quantify brain amyloid in which a subject's T1 magnetic resonance imaging (MRI) and amyloid positron emission tomography (PET) scans are registered and warped to Montreal Neurological Institute 152 space using prescribed procedures. The method has a high failure rate in Down syndrome (DS) subjects from the Neurodegeneration in Aging Down Syndrome (NiAD) project. We evaluate imaging preprocessing methods (PMs) to improve the DS success rate.

METHODS: PMs were constructed from combinations of image origin reset, filtering, MRI bias correction, and MRI skull stripping. Centiloid results were evaluated for adherence to standards using The Global Alzheimer's Association Interactive Network dataset. PMs were also evaluated using the NiAD dataset to judge their suitability for the DS population. DS PM evaluation procedures were developed corresponding to those specified for non-DS populations.

RESULTS: Five accepted PMs improved the Centiloid-processing success rate in the DS cohort from 61.3% to 95.6%.

DISCUSSION: The identified combinations of preprocessing steps substantially improved the success rate of Centiloid processing in DS.

HIGHLIGHTS: Image preprocessing pipeline is proposed for Centiloid analysis of DS. Preprocessing pipelines are evaluated for adherence to Centiloid standards. Pipelines are evaluated for improvement in yield of usable imaging data. Preprocessing of amyloid imaging data resulted in a large yield improvement.},
}

Humans
*Down Syndrome/diagnostic imaging
*Magnetic Resonance Imaging/methods
Positron-Emission Tomography/methods
*Image Processing, Computer-Assisted/methods
*Brain/diagnostic imaging/metabolism
Male
Female
Middle Aged

@article {pmid41074749,
year = {2025},
author = {Huo, M and Mroz, EL and Monin, JK and Hinton, L},
title = {Support that people living with Alzheimer's disease provide to their spousal caregivers: a qualitative study on dyadic perspectives.},
journal = {Aging & mental health},
volume = {},
number = {},
pages = {1-11},
doi = {10.1080/13607863.2025.2569657},
pmid = {41074749},
issn = {1364-6915},
abstract = {OBJECTIVES: Research extensively examines spousal caregiving in dementia, but it remains unclear how both partners perceive the support that caregivers receive from their spouses with Alzheimer's disease (AD). We present a qualitative investigation of pleasant and stressful experiences in both partners when such support occurs.

METHOD: Seventy-two couples managing mild-to-moderate AD responded to open-ended prompts about their pleasant and stressful experiences when people living with AD (PLWD) provided support to their spousal caregivers. We applied descriptive content analysis to examine these responses.

RESULTS: PLWD had pleasant experiences when perceiving their support to caregivers enhanced caregivers' well-being and promoted their own feelings of self-worth. Caregivers had pleasant experiences when support they received promoted their own well-being, reflected PLWD's preserved capabilities, and made PWLD happy. Regarding stressful experiences, PLWD noted that at times they could not help as much as they wished or were expected to, which, for some, promoted their sense of uselessness or a lack of caregiver appreciation. Caregivers had stressful experiences primarily due to frustration with the poor quality of support they received.

CONCLUSION: Findings inform the development of dyadic interventions for facilitating, while addressing the challenges of, mutual, changing support dynamics among spouses coping with AD.},
}

@article {pmid41074715,
year = {2025},
author = {Ajith, TA and Sreejith, JK},
title = {Microbiota-gut-brain axis and probiotics: potential therapeutic strategies for treating Alzheimer's disease.},
journal = {Nutritional neuroscience},
volume = {},
number = {},
pages = {1-17},
doi = {10.1080/1028415X.2025.2567429},
pmid = {41074715},
issn = {1476-8305},
abstract = {The gut-brain axis explains that changes in the intestinal microbiota influence Alzheimer's disease (AD). Short-chain fatty acids produced by the gut microbiome regulate the permeability of the gut and blood-brain barrier. Furthermore, they upregulate brain-derived neurotrophic factor, promote angiogenesis and neurogenesis, and control tau and Aβ proteins, microglial activity, apoptosis, oxidative damage, M1/M2 polarization of microglia, and neuroinflammation, which eventually improves cognitive impairment. This effect is mediated by modification of serotonin, dopamine, and γ-aminobutyric acid levels. Compared to healthy controls, mild cognitive impairment and AD were associated with low levels of Firmicutes and Bifidobacterium and high levels of Proteobacteria and Bacteroidetes. Lactobacillus and Bifidobacterium species were effective in improving cognitive function. More longitudinal research is needed to investigate precision medicine in patients with dysbiosis in the preclinical stages of the disease. This review describes the role of the gut microbiome and probiotics in AD.},
}

@article {pmid41074666,
year = {2025},
author = {Ye, Y and Sun, YHR and Oglesby, IK and Zheng, Y and Greene, CM},
title = {miR-17-5p: bridging the gap between disease mechanisms and therapeutic innovations.},
journal = {Epigenomics},
volume = {},
number = {},
pages = {1-16},
doi = {10.1080/17501911.2025.2572285},
pmid = {41074666},
issn = {1750-192X},
abstract = {MicroRNA-17-5p (miR-17-5p) is a regulatory molecule underpinning a range of diseases and for which various innovative therapeutic strategies across diverse pathologies are possible. Encoded by the miR-17-92 cluster, miR-17-5p exerts pleiotropic functions across cancers, inflammatory conditions, and genetic disorders such as cystic fibrosis (CF). Its capacity to fine-tune processes including autophagy, epithelial-mesenchymal transition, inflammation, and immune modulation places miR-17-5p at the nexus of disease progression and therapeutic intervention. In cancer, miR-17-5p exhibits context-dependent duality, acting as a tumor promoter or suppressor by regulating proliferation, metastasis, and therapeutic resistance pathways. In inflammatory and genetic diseases, including CF and neurodegenerative disorders, miR-17-5p orchestrates immune homeostasis, autophagy, and tissue remodeling, contributing to either disease exacerbation or resolution. Recent advances in RNA delivery technologies including nanocarriers, exosome-based systems, and receptor-targeted delivery platforms have unlocked new possibilities for miR-17-5p modulation with enhanced precision and minimized off-target effects. These innovations hold promise for restoring cellular homeostasis in CF, Alzheimer's disease, and cancers by precisely tuning miR-17-5p expression to match disease-specific requirements. This review highlights the versatile role of miR-17-5p in diverse pathological processes and emphasizes its promise as a biomarker and therapeutic target, offering a path toward more personalized and effective treatments across multiple disease areas.},
}

@article {pmid41074651,
year = {2025},
author = {Olchanyi, MD and Augustinack, J and Haynes, RL and Lewis, LD and Cicero, N and Li, J and Destrieux, C and Folkerth, RD and Kinney, HC and Fischl, B and Brown, EN and Iglesias, JE and Edlow, BL},
title = {Automated MRI Segmentation of Brainstem Nuclei Critical to Consciousness.},
journal = {Human brain mapping},
volume = {46},
number = {14},
pages = {e70357},
doi = {10.1002/hbm.70357},
pmid = {41074651},
issn = {1097-0193},
support = {DP2 HD101400/HD/NICHD NIH HHS/United States ; R01NS128961//NIH National Institute of Neurological Disorders and Stroke/ ; R21NS109627//NIH National Institute of Neurological Disorders and Stroke/ ; RF1NS115268//NIH National Institute of Neurological Disorders and Stroke/ ; U01NS086625//NIH National Institute of Neurological Disorders and Stroke/ ; U01NS132181//NIH National Institute of Neurological Disorders and Stroke/ ; U01NS137484//NIH National Institute of Neurological Disorders and Stroke/ ; U24NS135561//NIH National Institute of Neurological Disorders and Stroke/ ; U54NS115322//NIH National Institute of Neurological Disorders and Stroke/ ; RF1MH123195//NIH National Institute of Mental Health/ ; T32EB001680//NIH National Institute of Biomedical Imaging and Bioengineering/ ; W81XWH2210999//US Department of Defense/ ; R01AG070988//NIH National Institute on Aging/ ; U19AG024904//NIH National Institute on Aging/ ; ARUK-IRG2019A-003//Alzheimer's Research UK Interdisciplinary Grant/ ; 677697//European Research Council Starting Grant/ ; //Rappaport Foundation/ ; //MIT-Takeda Fellowship/ ; //James S. McDonnell Foundation/ ; //MIT/MGH Brain Arousal State Control Innovation Center (BASCIC) Project/ ; //Chen Institute MGH Research Scholar Award/ ; //NIH Blueprint for Neuroscience Research/ ; //McDonnell Center for Systems Neuroscience, Washington University/ ; //Northern California Institute for Research and Education/ ; /CAPMC/CIHR/Canada ; //Foundation for the National Institutes of Health (FNIH)/ ; //AbbVie/ ; /ALZ/Alzheimer's Association/United States ; //Alzheimer's Drug Discovery Foundation/ ; //Araclon Biotech/ ; //BioClinica Inc./ ; //Biogen/ ; //Bristol-Myers Squibb Company/ ; //CereSpir Inc./ ; //Cogstate/ ; //Eisai Inc./ ; //Elan Pharmaceuticals Inc./ ; //Eli Lilly and Company/ ; //EuroImmun/ ; //F. Hoffmann-La Roche Ltd./ ; //Genentech Inc./ ; //Fujirebio/ ; //GE Healthcare/ ; //IXICO Ltd./ ; //Janssen Alzheimer Immunotherapy Research & Development LLC/ ; //Johnson & Johnson Pharmaceutical Research & Development LLC/ ; //Lumosity/ ; //Lundbeck/ ; //Merck & Co. Inc./ ; //Meso Scale Diagnostics LLC/ ; //NeuroRx Research/ ; //Neurotrack Technologies/ ; //Novartis Pharmaceuticals Corporation/ ; //Pfizer Inc./ ; //Piramal Imaging/ ; //Servier/ ; //Takeda Pharmaceutical Company/ ; //Transition Therapeutics/ ; },
mesh = {Humans ; *Brain Stem/diagnostic imaging/physiology/anatomy & histology ; *Consciousness/physiology ; *Magnetic Resonance Imaging/methods ; Adult ; Male ; Female ; *Image Processing, Computer-Assisted/methods ; Middle Aged ; Brain Injuries, Traumatic/diagnostic imaging/pathology ; Bayes Theorem ; Reproducibility of Results ; Aged ; Atlases as Topic ; Algorithms ; },
abstract = {Although substantial progress has been made in mapping the connectivity of cortical networks responsible for conscious awareness, neuroimaging analysis of subcortical networks that modulate arousal (i.e., wakefulness) has been limited by a lack of robust segmentation procedures for ascending arousal network (AAN) nuclei in the brainstem. Automated segmentation of brainstem AAN nuclei is an essential step toward elucidating the physiology of human consciousness and the pathophysiology of disorders of consciousness. We created a probabilistic atlas of 10 AAN nuclei built on diffusion MRI scans of 5 ex vivo human brain specimens imaged at 750 μm isotropic resolution. The neuroanatomic boundaries of AAN nuclei were manually annotated with reference to 200 μm 7 Tesla MRI scans in all five specimens and nucleus-specific immunostains in two of the scanned specimens. We then developed a Bayesian segmentation algorithm that utilizes the probabilistic atlas as a generative model and automatically identifies AAN nuclei in a resolution- and contrast-adaptive manner. The segmentation method displayed high accuracy when applied to in vivo T1 MRI scans of healthy individuals and patients with traumatic brain injury, as well as high test-retest reliability across T1 and T2 MRI contrasts. Finally, we show through classification and correlation assessments that the algorithm can detect volumetric changes and differences in magnetic susceptibility within AAN nuclei in patients with Alzheimer's disease and traumatic coma, respectively. We release the probabilistic atlas and Bayesian segmentation tool to advance the study of human consciousness and its disorders. Trial Registration: ClinicalTrials.gov: NCT03504709.},
}

Humans
*Brain Stem/diagnostic imaging/physiology/anatomy & histology
*Consciousness/physiology
*Magnetic Resonance Imaging/methods
Adult
Male
Female
*Image Processing, Computer-Assisted/methods
Middle Aged
Brain Injuries, Traumatic/diagnostic imaging/pathology
Bayes Theorem
Reproducibility of Results
Aged
Atlases as Topic
Algorithms

@article {pmid41074442,
year = {2025},
author = {Chaplygina, A and Zhdanova, D},
title = {Modulation of Mitochondrial Dynamics in Primary Hippocampal Cultures of 5xFAD Mice by Mdivi-1, MFP, and Exogenous Zinc.},
journal = {Frontiers in bioscience (Landmark edition)},
volume = {30},
number = {9},
pages = {44648},
doi = {10.31083/FBL44648},
pmid = {41074442},
issn = {2768-6698},
support = {23-25-00485//Russian Science Foundation (RSF)/ ; },
mesh = {Animals ; *Mitochondrial Dynamics/drug effects ; *Hippocampus/metabolism/drug effects/cytology ; Mice, Transgenic ; *Zinc/pharmacology ; Reactive Oxygen Species/metabolism ; *Quinazolinones/pharmacology ; Amyloid beta-Peptides/metabolism ; Mitochondria/metabolism/drug effects ; Mice ; *Alzheimer Disease/metabolism/pathology ; Cells, Cultured ; Neurons/metabolism/drug effects ; Lipofuscin/metabolism ; Humans ; *Mitochondrial Proteins/metabolism ; Peptide Fragments/metabolism ; Astrocytes/metabolism/drug effects ; },
abstract = {BACKGROUND: Mitochondrial dynamics-the balance between fission, fusion, and mitophagy-are essential for maintaining cellular homeostasis and are increasingly implicated in the pathogenesis of Alzheimer's disease (AD).

METHODS: Here, we investigated the effects of targeted modulation of mitochondrial fission and fusion on mitochondrial morphology and metabolic status in primary hippocampal cultures derived from 5xFAD transgenic mice. Mitochondrial dynamics were modulated using the fission inhibitor Mitochondrial Division Inhibitor 1 (Mdivi-1), the fusion promoter mitochondrial fusion promoter M1 (MFP M1), and exogenous zinc as a fission activator. We evaluated mitochondrial morphology, lipofuscin accumulation, beta-amyloid (Aβ42) levels, and reactive oxygen species (ROS). The general condition of the cultures was assessed morphologically using neuronal and astrocytic markers.

RESULTS: Modulating mitochondrial dynamics altered mitochondrial morphology, decreased Aβ42, lipofuscin, and ROS levels, and improved cellular organization. Treatments with MFP and Mdivi-1 promoted mitochondrial hyperfusion without complete network integration and were associated with reduced astrogliosis and increased neuronal density. In contrast, zinc induced dose-dependent mitochondrial fragmentation and astrocytic clasmatodendrosis, with lower concentrations enhancing Aβ clearance and higher concentrations inducing toxicity.

CONCLUSIONS: Mitochondrial fusion and fission significantly influence lipofuscin and amyloid accumulation in 5xFAD cultures, underscoring their potential as therapeutic targets in neurodegenerative diseases. We propose that mitochondrial morphology acts as a key regulator of both cellular homeostasis and disease pathology.},
}

Animals
*Mitochondrial Dynamics/drug effects
*Hippocampus/metabolism/drug effects/cytology
Mice, Transgenic
*Zinc/pharmacology
Reactive Oxygen Species/metabolism
*Quinazolinones/pharmacology
Amyloid beta-Peptides/metabolism
Mitochondria/metabolism/drug effects
Mice
*Alzheimer Disease/metabolism/pathology
Cells, Cultured
Neurons/metabolism/drug effects
Lipofuscin/metabolism
Humans
*Mitochondrial Proteins/metabolism
Peptide Fragments/metabolism
Astrocytes/metabolism/drug effects

@article {pmid41074418,
year = {2025},
author = {Jang, H and Lee, S and Kim, YJ and Lee, J and Kim, SW and Son, Y and Kim, JS and Park, JH and Youn, B and Moon, C},
title = {Progressive Hippocampal Neuroarchitecture Changes in the 5×FAD Alzheimer's Disease Mouse Model.},
journal = {Journal of integrative neuroscience},
volume = {24},
number = {9},
pages = {40831},
doi = {10.31083/JIN40831},
pmid = {41074418},
issn = {0219-6352},
support = {RS-2022-NR069130//National Research Foundation (NRF) of Korea/ ; RS-2022-NR070407//National Research Foundation (NRF) of Korea/ ; RS-2023-00219517//National Research Foundation (NRF) of Korea/ ; //Korea Institute of Planning and Evaluation for Technology in Food, Agriculture and Forestry (IPET)/ ; RS-2024-00398561//Agriculture and Food Convergence Technologies Program for Research Manpower development/ ; },
mesh = {Animals ; *Alzheimer Disease/pathology/metabolism/physiopathology ; Disease Models, Animal ; Mice ; *Neuronal Plasticity/physiology ; *Hippocampus/pathology/metabolism ; Mice, Transgenic ; Male ; Dendritic Spines/pathology ; Disease Progression ; Behavior, Animal/physiology ; Mice, Inbred C57BL ; tau Proteins/metabolism ; },
abstract = {BACKGROUND: Neuroplasticity and synaptic homeostasis are essential in regulating neuronal activity and behavioral functions within the hippocampus. Alzheimer's disease (AD) is characterized by progressive cognitive decline, pathological accumulation of amyloid β (Aβ) plaques and tau neurofibrillary tangles, neuroinflammation, and synaptic dysfunction. However, the temporal progression of neuroplasticity-related impairments in the hippocampus, a region particularly vulnerable to AD pathology, is not completely understood.

METHODS: This study examined age-dependent changes in behavioral performance and hippocampal structural plasticity in the 5×FAD (five familial Alzheimer's disease) mouse model at 3, 6, and 12 months of age.

RESULTS: The 5×FAD mice exhibited progressive impairments in fine motor coordination and hippocampal-dependent working memory compared to control. Corresponding increases were observed in the accumulation of Aβ and phosphorylated tau, glial activation, and inflammatory cytokine production in the hippocampus across all time points. Golgi staining revealed significant age-related reductions in dendritic complexity, including fiber crossing counts, total dendritic length, and branch points in the cornu ammonis 1 (CA1) and dentate gyrus (DG) hippocampal subregions. Dendritic spine density and morphology exhibited significant alterations in the CA1 apical/basal and DG subregions with advancing age. Furthermore, the expression of synaptic proteins, including activity-regulated cytoskeleton-associated protein (Arc) and postsynaptic density protein-95 (PSD-95), significantly declined at 6 and 12 months of age.

CONCLUSIONS: Our findings suggest a potential relationship between AD-related protein pathology, neuroinflammation, and structural plasticity impairments in the hippocampus. Collectively, these changes may contribute to disrupted synaptic transmission and behavioral deficits associated with AD pathology.},
}

Animals
*Alzheimer Disease/pathology/metabolism/physiopathology
Disease Models, Animal
Mice
*Neuronal Plasticity/physiology
*Hippocampus/pathology/metabolism
Mice, Transgenic
Male
Dendritic Spines/pathology
Disease Progression
Behavior, Animal/physiology
Mice, Inbred C57BL
tau Proteins/metabolism

@article {pmid41074409,
year = {2025},
author = {Potokiri, A and Wang, H},
title = {Proteostasis and Neuroinflammation in Alzheimer's Disease.},
journal = {Journal of integrative neuroscience},
volume = {24},
number = {9},
pages = {39826},
doi = {10.31083/JIN39826},
pmid = {41074409},
issn = {0219-6352},
support = {RF1 AG072510/AG/NIA NIH HHS/United States ; },
mesh = {Humans ; *Alzheimer Disease/metabolism/immunology ; *Proteostasis/physiology ; *Neuroinflammatory Diseases/metabolism/immunology ; Animals ; },
abstract = {Alzheimer's disease (AD) is the most common cause of dementia in older adults, marked by a gradual and irreversible deterioration of cognitive abilities, including memory and thinking skills. AD is highly heterogeneous, with variations in amyloid and tau pathology, symptoms, proteostasis, neuroinflammation, and genetics. Dysregulated proteostasis and neuroinflammation, though usually protective, contribute significantly to disease progression. Proteostasis refers to the network that maintains the integrity of both intracellular and extracellular proteins, while neuroinflammation is the biological response to harmful stimuli. Proteostasis stress can activate immune responses and cause excessive inflammation, while impaired microglia and astrocyte function can further disrupt proteostasis and worsen disease progression. While numerous reviews on AD exist, this review focuses on the complex interplay between proteostasis and neuroinflammation in AD and their integral roles in disease pathology. Additionally, we will explore current and promising therapeutics targeting these processes, potential biomarkers, and the clinical trials conducted over the past 5 years, particularly those that address neuroinflammation and proteostasis, as identified through a PubMed search.},
}

Humans
*Alzheimer Disease/metabolism/immunology
*Proteostasis/physiology
*Neuroinflammatory Diseases/metabolism/immunology
Animals

@article {pmid41074172,
year = {2025},
author = {Chen, J and Zhang, X and Sun, J and Zhi, Y and Xie, Z and Guan, Y and Zhang, Z and Wu, C},
title = {Photothermal nano-agents: an innovative trident weapon for accurate and effective treatment of alzheimer's disease.},
journal = {Journal of nanobiotechnology},
volume = {23},
number = {1},
pages = {650},
pmid = {41074172},
issn = {1477-3155},
support = {82404876//National Natural Science Foundation of China/ ; 2024M760845//China Postdoctoral Science Foundation/ ; 2025T181064//China Postdoctoral Special Funding Project/ ; 232301420087//The Joint Fund of Science and Technology Development Program of Henan Province/ ; HN2025064//Postdoctoral funding in Henan Province/ ; },
mesh = {*Alzheimer Disease/therapy ; Humans ; *Photothermal Therapy/methods ; Animals ; Blood-Brain Barrier/metabolism/drug effects ; tau Proteins/metabolism ; Amyloid beta-Peptides/metabolism ; Infrared Rays ; *Nanoparticles/chemistry/therapeutic use ; Brain/metabolism ; Phototherapy/methods ; },
abstract = {Alzheimer's disease (AD) is a degenerative neurological illness for which effective therapy alternatives are currently lacking. Photothermal therapy (PTT) employs the localized thermal effects of nano-photothermal agents (NPTAs) under near-infrared (NIR) light for the treatment of diverse conditions. PTT presents numerous benefits for AD therapy, including operational flexibility, non-invasiveness, spatiotemporal modulation, and synergistic multimodal treatment approaches. The primary mechanisms of PTT for AD treatment encompass the following facets: Initially, localized heat impacts may transiently disrupt the blood-brain barrier (BBB), facilitating the trans-BBB transport of therapeutic medicines. Secondly, the photothermal action can efficiently dissociate Aβ aggregates and Tau protein while inhibiting Aβ aggregation, hence diminishing neurotoxicity and reinstating cognitive function. Third, during PTT, NPTAs can achieve imaging of biomarkers such as Aβ and Tau at the site of AD lesions and actively monitor the therapy process. Despite being in its nascent stages for AD treatment and encountering numerous challenges, such as poor biocompatibility, inadequate penetration of deep brain tissue by NIR light, and cumulative toxicity risks, PTT remains a promising therapeutic strategy to overcome the limitations of AD treatment. This study elucidates the pathophysiology of AD, the processes by which NPTAs enter the brain, and the mechanism of NPTAs in AD theranostics, with a particular focus on current developments in NIR-activated NPTAs for AD treatment. It further discusses the challenges in this emerging field and proposes future research directions, thereby facilitating the clinical translation of PTT-based strategies in AD treatment.},
}

*Alzheimer Disease/therapy
Humans
*Photothermal Therapy/methods
Animals
Blood-Brain Barrier/metabolism/drug effects
tau Proteins/metabolism
Amyloid beta-Peptides/metabolism
Infrared Rays
*Nanoparticles/chemistry/therapeutic use
Brain/metabolism
Phototherapy/methods

@article {pmid41073674,
year = {2025},
author = {Woo, MS and Therriault, J and Hosseini, SA and Wang, YT and Macedo, AC and Rahmouni, N and Aumont, É and Servaes, S and Tissot, C and Fernandez-Arias, J and Trudel, L and Hall, B and Bezgin, G and Quispialaya-Socualaya, K and Goncalves, M and Chan, T and Stevenson, J and Zheng, Y and Mitchell, S and Hopewell, R and Pola, I and Tan, K and Di Molfetta, G and Lussier, FZ and Massarweh, G and Vitali, P and Soucy, JP and Gauthier, S and Ashton, NJ and Blennow, K and Pascoal, TA and Zetterberg, H and Benedet, AL and Rosa-Neto, P},
title = {Glia inflammation and cell death pathways drive disease progression in preclinical and early AD.},
journal = {EMBO molecular medicine},
volume = {},
number = {},
pages = {},
pmid = {41073674},
issn = {1757-4684},
support = {MOP-11-51-31; RFN 152985, 159815, 162303//Canadian Government | Canadian Institutes of Health Research (CIHR)/ ; MOP-11-51-31 -team 1//Canadian Consortium of Neurodegeneration and Aging/ ; NIRG-12-92090, NIRP-12-259245//Alzheimer's Association (AA)/ ; #ADSF-21-831376-C, #ADSF-21-831381-C, #ADSF-21-831377-C, and #ADSF-24-1284328-C//Alzheimer's Association (AA)/ ; ZEN-21-848495, SG-23-1038904 QC//Alzheimer's Association (AA)/ ; CFI Project 34874; 33397//Brain Canada Foundation/ ; 2020-VICO-279314//FRQ | Fonds de Recherche du Québec - Santé (FRQS)/ ; IT27627//Mitacs Graduate Fellowship/ ; F225864C02//Max E Binz Fellowship-Medicine/ ; M159875C51//Grad Excellence Award in Neurology and Neurosurgery/ ; 2023_EKMS.03//Else Kröner Fresenius Foundation/ ; WO 2835/1-1//Deutsche Forschungsgemeinschaft (DFG)/ ; S0199/10110/2025//Corona-Stiftung (Corona Foundation)/ ; #2023-00356, #2022-01018 and #2019-02397//Swedish Research Council/ ; #2017-00915 and #2022-00732//Swedish Research Council/ ; 101053962//European Union Horizon Europe research and innovation programme/ ; #ALFGBG-71320//Swedish State Support for Clinical Research/ ; #201809-2016862//Alzheimer Drug Discovery Foundation, USA/ ; #22HLT07//European Partnership on Metrology (EPM)/ ; #FO2022-0270//Swedish State/ ; #ALZ2022-0006, #FO2024-0048-TK-130 and FO2024-0048-HK-24//Swedish State/ ; 860197//European Union's Horizon 2020 research and innovation programme Marie Sklodowska-Curie grant/ ; JPND2021-00694//European Union Joint Programme - Neurodegenerative Disease Research/ ; UKDRI-1003//UK Dementia Research Institute (UK DRI)/ ; #AF-930351, #AF-939721, #AF-968270, and #AF-994551//Swedish Alzheimer Foundation/ ; #ALZ2022-0006, #FO2024-0048-TK-130 and FO2024-0048-HK-24//Swedish State/ ; #ALFGBG-965240 and #ALFGBG-1006418//ALF agreement/ ; JPND2019-466-236//European Union Joint Programme for Neurodegenerative Disorders/ ; },
abstract = {Accumulation of amyloid-β (Aβ) and neurofibrillary tangles (NFTs) are followed by the activation of glia cells and infiltration of peripheral immune cells that collectively accelerate neurodegeneration in preclinical AD models. Yet, the role of neuroinflammation for neuronal injury and disease progression in preclinical and early symptomatic AD remains elusive. Here, we combined multiplexed immunoassays and SomaScan proteomics of the cerebrospinal fluid (CSF) with MRI and PET brain imaging of people across the AD continuum to identify pathways that are associated with AD progression. Unbiased clustering revealed that glia-mediated inflammation, activation of cell death pathways (CDPs) and synaptic pathologies were among the earliest Aβ-induced changes, and were associated with disease progression in preclinical AD. Mediation analysis revealed that activation of CDPs were decisive drivers of inflammation in early symptomatic AD. The cycle of glia-mediated neuroinflammation and neuronal injury characterizes preclinical AD and has implications for novel treatment approaches.},
}

@article {pmid41073581,
year = {2025},
author = {Lanskey, JH and Jafarian, A and Hughes, LE and Karadag, M and Kocagoncu, E and Rouse, MA and Adams, NE and Naessens, M and Raymont, V and Woolrich, M and Singh, KD and Henson, RN and Rowe, JB},
title = {Alzheimer's disease and memantine effects on NMDA-receptor blockade: non-invasive in vivo insights from magnetoencephalography.},
journal = {Molecular psychiatry},
volume = {},
number = {},
pages = {},
pmid = {41073581},
issn = {1476-5578},
support = {ARUK-PG2017B-19//Alzheimer's Research UK (ARUK)/ ; 220258/WT_/Wellcome Trust/United Kingdom ; SUAG/092 G116788; SUAG/096 G116788//RCUK | MRC | Medical Research Foundation/ ; },
abstract = {To accelerate new treatments for Alzheimer's disease, there is the need for human pathophysiological biomarkers that are sensitive to treatment and disease mechanisms. In this proof-of-concept study, we assess new biophysical models of non-invasive human MEG imaging to test the pharmacological and disease modulation of NMDA-receptor inhibition. Magnetoencephalography was recorded during an auditory mismatch negativity paradigm from (1) neurologically-healthy people on memantine or placebo (n = 19, placebo-controlled crossover design); (2) people with Alzheimer's disease at baseline and 16-months (n = 42, amyloid-biomarker positive, longitudinal observational design). Optimised dynamic causal models inferred voltage-dependent NMDA-receptor blockade using Parametric Empirical Bayes to test group effects. The mismatch negativity amplitude was attenuated when Alzheimer's disease was more severe (lower baseline mini-mental state examination) and after follow-up (versus baseline). Memantine increased NMDA-receptor inhibition, compared to placebo. Alzheimer's disease reduced NMDA-receptor inhibition in proportion to severity and over time. In line with preclinical studies, we confirm in humans that memantine and Alzheimer's disease have opposing effects on NMDA-receptor inhibition. The ability to infer such receptor dynamics and pharmacology from non-invasive physiological recordings has wide applications, including the assessment of other neurological disorders and novel drugs intended for symptomatic or disease-modifying treatments.},
}

@article {pmid41073395,
year = {2025},
author = {Baik, K and Kang, M and Park, YJ and Chung, SJ and Oh, K and Koh, SB and Kang, SH},
title = {Twelve-year nationwide cohort study identifying risk factors for conversion from mild cognitive impairment to Alzheimer's disease.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {35418},
pmid = {41073395},
issn = {2045-2322},
support = {NRF-2022R1F1A1063966//National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT)/ ; grant number: 2022R1I1A1A01056956//Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Education/ ; No. O2400251//Korea University Guro Hospital (KOREA RESEARCH-DRIVEN HOSPITAL) grant/ ; },
mesh = {Humans ; *Alzheimer Disease/epidemiology/etiology ; *Cognitive Dysfunction/epidemiology ; Male ; Aged ; Female ; Risk Factors ; Aged, 80 and over ; Middle Aged ; Retrospective Studies ; Republic of Korea/epidemiology ; Disease Progression ; Incidence ; Proportional Hazards Models ; Adult ; },
abstract = {Mild cognitive impairment (MCI) is a pre-dementia phase preceding dementia of the Alzheimer's type (DAT). Despite numerous studies exploring the risk factors for the conversion from MCI to DAT, the results have been heterogeneous. This study aimed to investigate the incidence of the conversion from MCI to DAT and the risk factors contributing to DAT conversion in Korean patients with MCI. A 12-year nationwide retrospective study was conducted. We enrolled patients with MCI aged ≥ 40 years between 2009 and 2015 and followed them up until 2020. The incidence of DAT conversion based on age at MCI diagnosis and its risk factors were analyzed using Cox proportional hazards regression. The conversion rate of DAT in patients with MCI increased during the age range of 70 to 90 years, and approached a plateau near the age of 100 years. Being underweight (hazard ratio [HR] 1.279, 95% confidence interval [CI] 1.223-1.338) was associated with a higher risk of DAT conversion. Cardiometabolic diseases (diabetes, HR 1.373, 95% CI 1.342-1.406; coronary heart disease, HR 1.047, 95% CI 1.015-1.079; and hemorrhagic stroke, HR 1.342, 95% CI 1.296-1.390;) increased the risk of DAT conversion, whereas hypertension, ischemic stroke, and dyslipidemia did not. Depression (HR 1.736, 95% CI 1.700-1.773) and physical inactivity (HR 1.193, 95% CI 1.161-1.227) were related to the increased risk. Mild (HR 0.860, 95% CI 0.830-0.891) to moderate (HR 0.880, 95% CI 0.837-0.926) alcohol consumption, high income (HR 0.947, 95% CI 0.925-0.970), and urban residence (HR 0.889, 95% CI 0.872-0.907) were associated with the decreased risk of DAT conversion. Multiple modifiable risk factors were closely associated with an increased risk of DAT conversion. Our results may help in designing preventive strategies to mitigate the risk of DAT conversion in patients with MCI.},
}

Humans
*Alzheimer Disease/epidemiology/etiology
*Cognitive Dysfunction/epidemiology
Male
Aged
Female
Risk Factors
Aged, 80 and over
Middle Aged
Retrospective Studies
Republic of Korea/epidemiology
Disease Progression
Incidence
Proportional Hazards Models
Adult

@article {pmid41073371,
year = {2025},
author = {Liu, RY and Yin, KF and He, SY and Su, WM and Duan, QQ and Wen, XJ and Chen, T and Shen, C and Li, JR and Cao, B and Chen, YP},
title = {Viral infections and the risk of neurodegenerative diseases: a comprehensive meta-analysis and systematic review.},
journal = {Translational psychiatry},
volume = {15},
number = {1},
pages = {388},
pmid = {41073371},
issn = {2158-3188},
mesh = {Humans ; *Neurodegenerative Diseases/epidemiology/virology ; *Virus Diseases/epidemiology/complications ; *Amyotrophic Lateral Sclerosis/epidemiology/virology ; *Parkinson Disease/epidemiology/virology ; Risk Factors ; *Alzheimer Disease/epidemiology/virology ; },
abstract = {BACKGROUND: Viral infections have been implicated in the pathogenesis of neurodegenerative diseases (NDs); however, evidence linking specific viruses to Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) remains inconclusive. This study conducted a meta-analysis and systematic review to investigate these associations.

METHODS: Thorough searches were conducted across Embase, PubMed, Cochrane Library, Web of Science and Scopus until May 18, 2025, to identify observational studies investigating the relationship between viral infections and the risk of NDs, including AD, PD, and ALS. Meta-analyses were executed using a random-effects model with Stata MP18.0.

RESULTS: A total of 34,417 articles were identified, of which 73 met the eligibility criteria for inclusion in the meta-analysis, and 48 were included in the systematic review. The analysis demonstrated that infections with cytomegalovirus (CMV) (odds ratio [OR] = 1.41; 95% confidence interval [CI]: 1.03, 1.93), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (OR = 1.88; 95% CI: 1.53, 2.32), hepatitis C virus (HCV) (OR = 1.39; 95% CI: 1.14, 1.69), and human herpesvirus (HHV) (OR = 1.24; 95% CI: 1.02, 1.51) were associated with an increased risk of AD. Regarding PD, infections with hepatitis B virus (HBV) (OR = 1.18; 95% CI: 1.04, 1.35) and HCV (OR = 1.29; 95% CI: 1.18, 1.41) were identified as risk factors. Conversely, no significant correlation was found between any viral infection and the risk of ALS.

CONCLUSION: This meta-analysis supports the role of select viral infections in AD and PD pathogenesis. However, no association was found between viral infections and ALS, warranting further large, multicenter, and longitudinal studies to elucidate mechanisms and confirm causality.},
}

Humans
*Neurodegenerative Diseases/epidemiology/virology
*Virus Diseases/epidemiology/complications
*Amyotrophic Lateral Sclerosis/epidemiology/virology
*Parkinson Disease/epidemiology/virology
Risk Factors
*Alzheimer Disease/epidemiology/virology

@article {pmid41073365,
year = {2025},
author = {Hazelton, JL and Migeot, J and Gonzalez-Gomez, R and Altschuler, F and Duran-Aniotz, C and Wen, O and Galván Rial, DS and Barttfeld, P and Medel, V and González Campo, C and Castro-Laguardia, AM and Hernández, H and Gonzalez-Silva, C and Castaner, O and Hu, K and Li, P and Behrens, MI and Bruno, MA and Cardona, JF and Custodio, N and Santamaria-Garcia, H and Garcia, AM and Godoy, ME and Avila-Funes, JA and Maito, M and Matallana, DL and Miller, B and Lopera, F and Okada de Oliveira, M and Pina-Escudero, SD and Possin, KL and de Paula France Resende, E and Reyes, P and Slachevsky, A and Sosa, AL and Takada, LT and Yokoyama, JS and Ibanez, A},
title = {Cardiovascular risk factors and the allostatic interoceptive network in dementia.},
journal = {Cardiovascular research},
volume = {},
number = {},
pages = {},
doi = {10.1093/cvr/cvaf185},
pmid = {41073365},
issn = {1755-3245},
abstract = {AIMS: Cardiovascular risk factors, such diabetes, hypertension, blood pressure, obesity, and smoking, are linked with allostatic-interoception - the continuous monitoring of internal bodily states in anticipation of environmental demands. These risk factors are associated with dementia risk. How these factors affect brain networks vulnerable to neurodegeneration and involved in allostatic-interoception, such as the Allostatic-Interoceptive Network (AIN), is unknown. We investigated the relationship between cardiovascular risk and AIN structure and function in frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD).

METHODS AND RESULTS: We recruited 1501 participants (304 with FTLD, 512 with AD, and 685 healthy controls) from the Multi-Partner Consortium to Expand Dementia Research in Latin America (ReDLat). A cardiovascular risk score was calculated based on: age, sex, diabetes, hypertension, systolic blood pressure, body mass index, and smoking status. Cardiovascular risk was associated with gray matter integrity and functional connectivity in age- and sex-matched patient-control groups focusing on predefined regions of interest within the AIN.Higher cardiovascular risk was associated with reduced structural integrity and functional connectivity within the AIN in both FTLD and AD. FTLD patients showed more extensive structural and functional connectivity disruptions throughout the AIN. In AD patients, structural reductions in the AIN were prominent, with functional connectivity restricted to the hippocampus, parahippocampal gyrus, and orbitofrontal regions.

CONCLUSIONS: Cardiovascular risk factors appear to adversely impact the AIN structure and function, with disease-specific patterns of vulnerability. Results underscore the importance of integrating cardiovascular health into models of neurodegenerative disease and managing cardiovascular health to support brain integrity in dementia.},
}

@article {pmid41073025,
year = {2025},
author = {Zhang, X and Cao, J and Chen, X and Gan, N and Huang, S},
title = {Nanoflower-structured MnO2/Au composites with enhanced catalytic performance for colorimetric assay of α-glucosidase.},
journal = {Analytica chimica acta},
volume = {1376},
number = {},
pages = {344632},
doi = {10.1016/j.aca.2025.344632},
pmid = {41073025},
issn = {1873-4324},
mesh = {*Manganese Compounds/chemistry ; *Colorimetry/methods ; *Oxides/chemistry ; *Gold/chemistry ; *alpha-Glucosidases/metabolism/analysis/blood ; Humans ; Catalysis ; Benzidines/chemistry ; Limit of Detection ; *Nanocomposites/chemistry ; *Nanostructures/chemistry ; Biocatalysis ; },
abstract = {BACKGROUND: α-Glucosidase (α-Glu) is an essential hydrolase that catalyzes the final step of carbohydrate digestion, playing a central role in glucose metabolism. Abnormal α-Glu activity is closely associated with type II diabetes, obesity, and Alzheimer's disease, making its precise monitoring critical for disease diagnosis and therapeutic evaluation. However, conventional detection methods often depend on natural enzymes or sophisticated nanomaterials, which face challenges of high cost, instability, and complicated operation. Thus, developing a simple, robust, and cost-effective strategy for sensitive α-Glu detection is of great significance.

RESULTS: In this study, a simple, low-cost, and sensitive colorimetric assay for α-Glu activity was developed based on nanozyme catalysis. Flower-like MnO2/Au composites were synthesized via a mild and facile method, exhibiting remarkable oxidase-like activity. The MnO2/Au nanozyme could efficiently catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) by dissolved oxygen, producing a distinct blue color as the initial signal. In the presence of α-Glu, its substrate α-arbutin was hydrolyzed to generate hydroquinone, a strong reductant that rapidly reduced oxidized TMB (blue) to its colorless form, resulting in a visible signal decrease. This "color-on/color-off" mechanism enabled sensitive α-Glu detection without the need for natural enzymes or additional oxidants. The method demonstrated a low detection limit (0.005 U/mL), wide linear range, and excellent reproducibility. Recovery experiments in spiked human serum showed satisfactory results (97.7-103.2 %), confirming the robustness of the assay in complex biological matrices.

SIGNIFICANCE: Compared with conventional methods, the proposed nanozyme-based strategy integrates ease of synthesis, mild reaction conditions, and cost-effectiveness with reliable analytical performance, highlighting its potential for rapid clinical screening and inhibitor discovery. This work not only expands the application of MnO2-based nanozymes in biosensing but also provides a versatile platform for detecting hydrolytic enzyme activity through product-triggered signal modulation.},
}

*Manganese Compounds/chemistry
*Colorimetry/methods
*Oxides/chemistry
*Gold/chemistry
*alpha-Glucosidases/metabolism/analysis/blood
Humans
Catalysis
Benzidines/chemistry
Limit of Detection
*Nanocomposites/chemistry
*Nanostructures/chemistry
Biocatalysis

@article {pmid41073019,
year = {2025},
author = {Li, A and Yu, Y and Zhang, Z and Wufuer, R and Wang, D and Zhang, L},
title = {Pd-modified MXene enabled electrochemical sensing platform for ratiometric detection of acetylcholinesterase inhibitors via modulation effect of Prussian blue.},
journal = {Analytica chimica acta},
volume = {1376},
number = {},
pages = {344625},
doi = {10.1016/j.aca.2025.344625},
pmid = {41073019},
issn = {1873-4324},
mesh = {*Ferrocyanides/chemistry ; *Electrochemical Techniques/methods ; *Cholinesterase Inhibitors/analysis ; *Palladium/chemistry ; Acetylcholinesterase/metabolism ; Humans ; Limit of Detection ; *Nanocomposites/chemistry ; *Metal Nanoparticles/chemistry ; Electrodes ; Nitrites ; Transition Elements ; },
abstract = {BACKGROUND: Sensitive detection of acetylcholinesterase (AChE) inhibitors is crucial for pharmaceutical screening, managing neurodegenerative diseases, and drug development. However, their therapeutic use is often limited by toxicity and side effects. Current detection methods for AChE inhibitors suffer from issues like low sensitivity, high cost, and interference from complex biological matrices. Therefore, there is a growing and urgent demand for sensitive, reliable, and cost-effective sensors that enable early diagnosis, accurate monitoring of drug efficacy, and personalized treatment plans in various clinical settings.

RESULTS: In this work, a novel ratiometric electrochemical sensor was developed using Pd-modified MXene integrated with Prussian blue (PB) nanocomposites for AChE inhibitor detection. The Pd-modified MXene provides high electrical conductivity and abundant surface sites for nanoparticle immobilization, enhancing electron transfer and signal strength. Pd nanoparticles improve the electrocatalytic activity of the electrode, boosting electron transfer. PB acted as a redox mediator that oxidized thiocholine (TCh), the enzymatic product of AChE-catalyzed hydrolysis of ATCh, and was reoxidized to generate a stable redox potential serving as an internal reference. This enabled dual-signal ratiometric detection, improving accuracy and resistance to background interference. Using berberine as a model inhibitor, the sensor exhibited a linear range of 0.13-41 μmol/L and a detection limit of 10.0 nmol/L. The sensor demonstrated excellent reproducibility, retaining 93.1 % of its initial response after 28 days, and detected berberine in tablet and serum samples with high recovery, showing broad applicability.

SIGNIFICANCE: This work highlights the synergistic effects of Pd-MXene and PB, offering a portable, cost-effective strategy for highly sensitive AChE inhibitor detection. The dual-signal ratiometric detection system enhances both sensitivity and accuracy, making it ideal for biomedical and pharmaceutical applications, with significant potential for early diagnosis and monitoring of neurodegenerative diseases.},
}

*Ferrocyanides/chemistry
*Electrochemical Techniques/methods
*Cholinesterase Inhibitors/analysis
*Palladium/chemistry
Acetylcholinesterase/metabolism
Humans
Limit of Detection
*Nanocomposites/chemistry
*Metal Nanoparticles/chemistry
Electrodes
Nitrites
Transition Elements

@article {pmid41072777,
year = {2025},
author = {Kahraman, Ç and Gönülalan, EM and Koçak, E and Gökmen, FŞ and Gündüz, MG and Nemutlu, E and Tatlı Çankaya, Iİ},
title = {Non-targeted metabolomic profiling of Cistus species and association with anticholinesterase efficacy for Alzheimer's disease: In vitro and in silico evaluation.},
journal = {Journal of ethnopharmacology},
volume = {},
number = {},
pages = {120692},
doi = {10.1016/j.jep.2025.120692},
pmid = {41072777},
issn = {1872-7573},
abstract = {Alzheimer's disease (AD) is characterized by decreased glucose utilization, and insulin therapy has been associated with improved memory. Therefore, AD is suggested to be classified as "Type 3 diabetes". Cistus L. species are traditionally used to treat diabetes, which is highly associated with AD, and the potential of this genus for treating AD has not been sufficiently investigated.

AIM: This study focused on the untargeted metabolomic profiling of methanolic extracts from five Cistus species to investigate the correlation between the metabolites and bioactivity.

MATERIALS AND METHODS: Gas chromatography-mass spectrometry and liquid chromatography quadrupole time-of-flight mass spectrometry were employed for metabolomics analysis. The inhibitory activity of the extracts on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), as well as their antioxidant capacity, were assessed. Additionally, molecular modeling techniques were utilized to corroborate the correlation between the metabolites and their cholinesterase inhibitory potency.

RESULTS: The plant extracts demonstrated inhibitory effects on BChE with IC50 values ranging from 1.80 to 9.83 μg/mL, which were notably lower than those observed for AChE. Correlation analysis revealed that chlorogenic acid demonstrated strong correlations with AChE inhibitory activity, while sinapyl alcohol was closely associated with BChE inhibitory activity. Additionally, molecular modeling studies supported the inhibitory potential of these metabolites.

CONCLUSION: This study highlights the substantial cholinesterase inhibitory capabilities of Cistus species, with C. creticus demonstrating particularly strong activity against both AChE and BChE. The results indicate that extracts from these species could be valuable natural sources of active metabolites with potent cholinesterase inhibitory effects, presenting promising new options for AD therapy.},
}

@article {pmid41072770,
year = {2025},
author = {Overby, M and Desdorf, LM and Kjølbye, L and Rosendahl, T and Weick, JP and Schiøtt, B and Berglund, NA and Müller, HK},
title = {Transmembrane domain interactions underlie NSG1 regulation of sortilin ectodomain shedding.},
journal = {The Journal of biological chemistry},
volume = {},
number = {},
pages = {110804},
doi = {10.1016/j.jbc.2025.110804},
pmid = {41072770},
issn = {1083-351X},
abstract = {Sortilin is a single-pass transmembrane receptor involved in intracellular trafficking, neurotrophic signaling, and protein clearance pathways relevant to neurodegenerative disease. We recently identified the neuron-specific protein NSG1 as a selective modulator of sortilin function, promoting its ectodomain shedding via ADAM10. However, the molecular basis of this interaction remains unresolved. Here, we present a structural framework for NSG1-mediated regulation of sortilin shedding. Using mutagenesis, biochemical assays, and structural modeling, we mapped the interaction interface of NSG1 to the helical transmembrane domain (TMD) of sortilin. We show that NSG1 binds a specific interface within the sortilin TMD, modulating its susceptibility to ectodomain shedding. Mutational analysis revealed that substitutions in the central region of the sortilin TMD, particularly T770W and A773W, significantly reduce NSG1-dependent shedding without disrupting complex formation. Coarse-grained molecular dynamics simulations identified two potential binding interfaces on the sortilin TMD and demonstrated that the T770W mutation shifts the preferred interface, thereby diminishing the ability of NSG1 to promote proteolytic processing. Notably, the closely related protein NSG2 has a different preferred binding mode on the sortilin TMD and does not induce shedding, highlighting the functional specificity of NSG1. Our findings establish the TMD-TMD interaction as an important basis for NSG1-mediated regulation of sortilin shedding. This study advances our understanding of how transmembrane interactions govern substrate-specific ADAM proteolysis and provides new insight into the molecular control of sortilin function. Given the emerging role of sortilin in Alzheimer's disease, these insights may help clarify how its processing is regulated in the diseased brain.},
}

@article {pmid41072666,
year = {2025},
author = {Wang, R and Zhang, R and Zhou, J and Ran, J},
title = {Crosstalk between anti-angiogenic and pro-angiogenic pathways in disease: Mechanisms and therapeutic strategies.},
journal = {Pharmacology & therapeutics},
volume = {},
number = {},
pages = {108934},
doi = {10.1016/j.pharmthera.2025.108934},
pmid = {41072666},
issn = {1879-016X},
abstract = {Angiogenesis, which entails the sprouting of new blood vessels from existing ones, is a critical process in normal development and tissue repair. However, when dysregulated, it contributes to a variety of diseases, including cancer, ischemic disorders, and chronic inflammation. Central to these processes are key factors such as vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and platelet-derived growth factor (PDGF). Recent research has focused on therapeutic modulation of angiogenesis, employing both anti-angiogenic and pro-angiogenic strategies to regulate these pathways. Anti-angiogenic therapies primarily target the VEGF pathway to inhibit vessel formation, thereby reducing tumor vascularization in cancer and preventing abnormal blood vessel growth in neovascular ocular diseases such as age-related macular degeneration and diabetic retinopathy. Conversely, pro-angiogenic therapies stimulate vessel growth to improve vascularization in conditions like coronary artery disease and Alzheimer's disease, enhancing tissue perfusion and promoting regeneration. In this review, we summarize current knowledge on targeted modulation of angiogenesis, detailing therapeutic strategies, the mechanisms that regulate vascular homeostasis, and their implications for disease management.},
}

@article {pmid41072413,
year = {2025},
author = {Wu, Z and Li, N and Luo, Z and Chen, Z and He, X and Shi, F and Han, J and Huang, H and Shi, B and Zhang, L and Li, Y and Shen, J and Bok, S and Sun, J and Niu, X and Mo, K and Yin, P and Leng, L and Wang, X and Zhang, J and Chen, L and Zhou, D and Cheng, W and Huang, J and Greenblatt, MB and Xu, R},
title = {The p75 neurotrophin receptor controls the skeletal stem cell niche through sensory innervation.},
journal = {Developmental cell},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.devcel.2025.09.012},
pmid = {41072413},
issn = {1878-1551},
abstract = {Low bone mass is frequently observed in Alzheimer's disease (AD), yet the underlying mechanisms remain poorly understood. In this study, we demonstrate that sensory nerves constitute a critical component of the skeletal stem cell (SSC) niche. Deletion of the neurotrophin receptor p75NTR in neurons or sensory-specific cells, but not in osteogenic or sympathetic cells, resulted in reduced sensory innervation, disrupted SSC homeostasis, and significant bone loss. Although a cell-intrinsic role of p75NTR in SSCs cannot be ruled out, further experiments involving sensory denervation or transplantation into hosts with sensory-neuron-specific p75NTR deficiency confirmed impaired SSC osteogenesis. Mechanistically, p75NTR controls the expression of neuronal osteopontin (SPP1), which in turn promotes SSC self-renewal and osteogenic differentiation. Notably, this p75NTR-SPP1 signaling axis was found to be disrupted in AD mouse models, offering a direct mechanistic explanation for AD-associated osteopenia and highlighting the therapeutic potential of targeting neural control of SSCs.},
}

@article {pmid41072188,
year = {2025},
author = {Pashova-Dimova, S and Petrov, P and Karachanak-Yankova, S and Belezhanska, D and Zhelev, Y and Mehrabian, S and Toncheva, D and Traykov, L and Pashov, A},
title = {Changes in the public IgM repertoire and its idiotypic connectivity in Alzheimer's disease and frontotemporal dementia.},
journal = {Journal of neuroimmunology},
volume = {409},
number = {},
pages = {578775},
doi = {10.1016/j.jneuroim.2025.578775},
pmid = {41072188},
issn = {1872-8421},
abstract = {Alzheimer's disease (AD) and frontotemporal dementia (FTD) are prevalent neurodegenerative disorders. Early diagnosis is challenging due to the lack of definitive biomarkers and reliance on invasive procedures. Immune biomarkers, particularly those reflecting the interaction between the central nervous system (CNS) and the peripheral immune system, have shown promise for non-invasive detection through blood samples. This study investigates the reactivity of serum IgM and IgG from AD and FTD patients against a library of mimotopes representing public IgM reactivities in healthy donors. Serum samples from AD, FTD, and other neurodegenerative dementias (ND) and controls were tested on peptide microarrays. The samples were pooled to mitigate individual variability. The reactivity data were analyzed using graphs to represent the cross-reactivity networks. The analysis revealed distinct reactivity patterns for the studied groups. Public IgM reactivities showed significant correlations with neurodegenerative conditions, with AD and FTD exhibiting loss or gain of specific IgM reactivities. Graph analysis highlighted significant differences between disease and control groups in graph density, clustering, and assortativity parameters. Mimotopes of IgM reactivities lost in dementia, particularly in AD, exhibited significant homology to HCDR3 sequences of human antibodies. Furthermore, clusters of reactivities showed significant distinctions between AD and FTD, with IgG reactivities providing additional differentiation. Several self-proteins related to neurodegeneration proved to have sequences homologous to disease-associated mimotopes. Interestingly, the beta-propeller signature sequence YWTD found in ApoE's receptor LRP1 proved a characteristic epitope for IgG in FTD but not AD. At the same time, the respective public gM mimotope YWTDSSR coincides with a highly conserved sequence in many microorganisms and sequences found in human HCDR3. Thus, the public IgM repertoire, characterized by its broad reactivity and inherent autoreactivity, offers valuable insights into the immunological alterations in neurodegenerative diseases. The study supports the potential of IgM and IgG reactivity profiles as another compartment of non-invasive biomarkers for early diagnosis and differentiating AD and FTD.},
}

@article {pmid41072129,
year = {2025},
author = {Guo, G and Wen, G and Liu, L and Song, R and Cao, P and Yang, J and Zaiane, OR},
title = {BrainOSM: Outlier screening for multi-view functional brain network analysis.},
journal = {Computer methods and programs in biomedicine},
volume = {273},
number = {},
pages = {109092},
doi = {10.1016/j.cmpb.2025.109092},
pmid = {41072129},
issn = {1872-7565},
abstract = {PURPOSE: Identifying biomarkers for mental diseases is vital for understanding their underlying mechanisms, facilitating early diagnosis, and enabling more personalized treatment strategies. In this study, we focus on diagnosing autism spectrum disorder (ASD) and alzheimer's disease (AD) by analyzing functional brain networks (FBNs), which are represented as graphs capturing the functional connectivity patterns of the brain. The primary challenges in modeling FBNs for this disorder stem from two key issues: (i) the heterogeneity among graphs, and (ii) the disease-unrelated information within graphs.

METHOD: We introduce a two-stage framework, BrainOSM, which combines outlier screening in datasets with a multi-view graph pooling module for enhanced graph classification. Specifically, the first stage employs progressive uncertainty-based outlier screening to reduce the interference of inter-graph heterogeneity. The second stage integrates multi-graph pooling, multi-view learning, and prior subnetwork regularization to refine graph structures, effectively tackling the challenge of disease-unrelated information within graphs.

RESULTS: To validate the effectiveness of our method, we assess its performance on two public datasets: the Autism Brain Imaging Data Exchange (ABIDE) dataset and the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. On the ABIDE dataset, BrainOSM achieved an average accuracy of 70.23% and an AUC of 70.42%, corresponding to improvements of 8.55% and 7.74% over the traditional GCN method. On the ADNI dataset, it reached an average accuracy of 82.29% and an AUC of 83.23%, showing gains of 8.97% and 11.78%, respectively. Our code is publicly available at https://github.com/guoguiliang111/BrainOSM.

CONCLUSION: Our extensive experiments confirm the generalizability and the effectiveness of BrainOSM for mental disease classification. Visual analyses further demonstrate that the model effectively identifies subnetworks associated with mental diseases, highlighting its potential for clinical interpretation. Moreover, our findings indicate that outlier screening plays a crucial role in improving classification accuracy when dealing with heterogeneous datasets.},
}

@article {pmid41072064,
year = {2025},
author = {Rezaie Pouya, M and Aghelan, Z and Hoseini, S and Rastegari, A and Khazaie, H},
title = {Associations of serum α-synuclein and 1,3-β-D-glucan levels with sleep architecture alterations in chronic insomnia disorder.},
journal = {Behavioural brain research},
volume = {496},
number = {},
pages = {115869},
doi = {10.1016/j.bbr.2025.115869},
pmid = {41072064},
issn = {1872-7549},
abstract = {BACKGROUND: Chronic insomnia disorder (CID) is a widespread sleep disorder linked to increased risks of various chronic diseases and often precedes neurodegenerative conditions such as Parkinson's and Alzheimer's disease. Emerging evidence suggests that gut microbiome disturbances contribute to CID through the gut-brain axis, involving microbial metabolites and neuroactive proteins.

OBJECTIVES: This study explored the relationships between serum 1,3-β-D-glucan (a marker of intestinal permeability and microbial translocation), alpha-synuclein (αSyn, a neuronal protein implicated in neurodegeneration), and sleep architecture in chronic insomnia individuals compared to healthy controls.

METHODS: Blood samples were taken from 15 people who had been diagnosed with CID, based on their results from the Pittsburgh Sleep Quality Index (PSQI) and video-polysomnography tests. For comparison, blood was also collected from 15 healthy volunteers, whose sleep quality was assessed using the PSQI. Serum concentrations of 1,3-β-D-glucan and αSyn protein were measured using enzyme-linked immunosorbent assay (ELISA).

RESULTS: The findings showed significantly elevated serum 1,3-β-D-glucan (p < 0.0001) and αSyn (p < 0.001) levels in the CID group, with a strong positive correlation between these markers (r = 0.964, p < 0.01). Moreover, increased αSyn levels were associated with alterations in sleep stages, particularly prolonged rapid eye movement (REM) sleep duration (r = 0.560, p < 0.05).

CONCLUSIONS: These findings support a mechanistic link between gut microbiota disruption, αSyn pathology, and altered sleep architecture in CID, highlighting novel pathways for understanding the neuroimmune mechanisms underlying sleep disturbances. Serum 1,3-β-D-glucan and αSyn may serve as potential biomarkers for identifying insomniac individuals at risk of synucleinopathies and offer novel targets for therapeutic intervention aimed at restoring gut health and improving sleep quality.},
}

@article {pmid41071940,
year = {2025},
author = {Kiaei, M and Amirazodi, E and Abroumand Gholami, A},
title = {A commentary on "Deep cervical lymphovenous anastomosis (LVA) for Alzheimer's Disease: microsurgical procedure in a prospective cohort study".},
journal = {International journal of surgery (London, England)},
volume = {},
number = {},
pages = {},
doi = {10.1097/JS9.0000000000003567},
pmid = {41071940},
issn = {1743-9159},
}

@article {pmid41071932,
year = {2025},
author = {Ruiz-Reig, N and Virosztek, M and Chehade, G and Suelves, N and Zola, NKN and Salman, Y and Schakman, O and Kienlen-Campard, P and Hanseeuw, B and Tissir, F},
title = {KIF2A downregulation links amyloid-β to Tau phosphorylation in Alzheimer's disease.},
journal = {Brain : a journal of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/brain/awaf382},
pmid = {41071932},
issn = {1460-2156},
abstract = {Microtubules (MT) are essential components of the cytoskeleton. Dysfunctions of MT and MT-associated proteins are prominent features of neurodegenerative disorders. In Alzheimer's disease (AD), changes in MT composition and hyperphosphorylation of Tau are more closely related to neurodegeneration than amyloid plaque formation. However, the accumulation of amyloid beta (Aβ) species is the earliest event in AD pathology and induces Tau toxicity. KIF2A is a microtubule depolarizing kinesin with important roles during cortical development. KIF2A expression is maintained in the mature brain, where it is required for neuronal survival. Here, we used a conditional approach to ablate KIF2A specifically in the adult mouse cortex and hippocampus to assess the impact of KIF2A deletion on neuronal survival and Tau phosphorylation. We found that KIF2A deficiency leads to a reduction of dendritic spine density and maturation associated with cognitive decline, followed by an increase in Tau phosphorylation through ERK1/2 activation. We also studied KIF2A expression in 5xFAD mouse model and post-mortem human brain tissue. We report that Aβ accumulation alters KIF2A expression in neurons and most importantly, KIF2A protein levels are drastically reduced in AD patients but not in patients with other primary Tauopathies. Our results shed light on the relationship between Aβ accumulation, KIF2A deregulation, microtubule dysfunction, and enhanced Tau phosphorylation in the context of AD.},
}

@article {pmid41071913,
year = {2025},
author = {Zhao, M and Yang, J and Cheng, H and Fan, Y and , },
title = {Altered brain morphometry and its association with cognitive decline and APOE gene in normal people at risk for Alzheimer's disease.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877251384967},
doi = {10.1177/13872877251384967},
pmid = {41071913},
issn = {1875-8908},
abstract = {BackgroundAlzheimer's disease (AD) is a progressive neurodegenerative disorder marked by cognitive decline and memory impairment. Identifying early markers of AD is critical for timely diagnosis and intervention.ObjectiveThis study aimed to characterize the neuropsychological and pathological features of cognitively unimpaired (CU) individuals who later progressed to mild cognitive impairment (MCI) or AD, referred to as At-Risk CU. The goal was to support accurate staging and inform early therapeutic strategies.MethodsParticipants were categorized into CU, At-Risk CU, MCI, and AD groups. Data analyses focused on neuroimaging scans, neuropsychological assessments, cerebrospinal fluid (CSF) biomarkers (including Aβ1-40/Aβ1-42 and p-Tau/t-Tau), and APOE genotypes. Voxel-based morphometry (VBM) was employed to assess gray matter (GM) volume and white matter (WM) integrity. Statistical analyses were conducted to evaluate group differences and associations.ResultsVBM revealed progressive GM atrophy and WM disruptions across the continuum from CU to At-Risk CU, MCI, and AD, particularly in the hippocampus and adjacent regions. Neuropsychological assessments showed significant cognitive decline across stages, while dynamic changes in CSF biomarkers in At-Risk CU suggested compensatory mechanisms. The APOE ε4 allele was strongly associated with AD progression, whereas the ε2 allele demonstrated protective effects. GM volume was significantly correlated with ADAS11 and ADAS13 scores.ConclusionsThis study identifies At-Risk CU as a distinct and clinically meaningful stage in AD progression, marked by structural, cognitive, and biomarker alterations. Integrating neuropsychological assessments, neuroimaging, and CSF biomarkers may facilitate early detection and enable targeted interventions to improve outcomes for individuals at elevated risk of AD.},
}

@article {pmid41071871,
year = {2025},
author = {Salcedo-Tacuma, D and Asad, N and Islam, MQ and Anderson, R and Smith, DM},
title = {Hyperactive 20S proteasome enhances proteostasis and ERAD in C. elegans via degradation of intrinsically disordered proteins.},
journal = {Science advances},
volume = {11},
number = {41},
pages = {eadx3014},
pmid = {41071871},
issn = {2375-2548},
mesh = {Animals ; *Caenorhabditis elegans/metabolism/genetics ; *Proteostasis ; *Endoplasmic Reticulum-Associated Degradation ; *Proteasome Endopeptidase Complex/metabolism/genetics ; *Intrinsically Disordered Proteins/metabolism ; *Caenorhabditis elegans Proteins/metabolism/genetics ; Unfolded Protein Response ; Oxidative Stress ; Humans ; Proteolysis ; },
abstract = {Age-related proteinopathies, including Alzheimer's and Parkinson's disease, are driven by toxic accumulation of misfolded and intrinsically disordered proteins (IDPs) that overwhelm cellular proteostasis. The proteasome clears these proteins, but its failure in disease remains unclear. We engineered a Caenorhabditis elegans model with a hyperactive 20S proteasome (α3ΔN) for selective 20S activation. α3ΔN markedly enhanced IDP and misfolded protein degradation, reduced oxidative damage, and improved endoplasmic reticulum-associated degradation (ERAD). Aggregation-prone substrates such as vitellogenins and human alpha-1 antitrypsin (ATZ) were efficiently cleared. Integrated proteomic and transcriptomic analyses reveal systemic adaptations featuring increased protein turnover and oxidative stress resistance independent of superoxide dismutases (SODs). Notably, α3ΔN extended life span and stress resistance independently of canonical unfolded protein response (UPR) signaling via xbp-1. These findings substantiate a "20S pathway" of proteostasis that directly alleviates protein aggregation and oxidative stress, offering a promising therapeutic angle for neurodegenerative diseases.},
}

Animals
*Caenorhabditis elegans/metabolism/genetics
*Proteostasis
*Endoplasmic Reticulum-Associated Degradation
*Proteasome Endopeptidase Complex/metabolism/genetics
*Intrinsically Disordered Proteins/metabolism
*Caenorhabditis elegans Proteins/metabolism/genetics
Unfolded Protein Response
Oxidative Stress
Humans
Proteolysis

@article {pmid41071767,
year = {2025},
author = {Novobilský, R and Kušnierová, P and Štěpán, D and Bártová, P and Stejskal, D and Bar, M},
title = {Identification and evaluation of potential microRNA markers for diagnostics in neurodegenerative diseases and correlation with other biochemical markers.},
journal = {PloS one},
volume = {20},
number = {10},
pages = {e0333801},
pmid = {41071767},
issn = {1932-6203},
mesh = {Humans ; *MicroRNAs/blood/genetics ; Biomarkers/blood ; Female ; Male ; *Neurodegenerative Diseases/diagnosis/genetics/blood ; Middle Aged ; Aged ; Alzheimer Disease/diagnosis/genetics/blood ; Case-Control Studies ; },
abstract = {OBJECTIVES: MicroRNAs (miRNA) are short, non-coding RNA molecules that play a crucial role in the development of organisms and are involved in various biological processes. They are considered potential biomarkers for many diseases, including neurodegenerative diseases. This study aimed to identify a set of microRNA targets that exhibited the greatest potential in successfully distinguishing and differentiating neurodegenerative diseases and to establish a correlation between selected miRNAs across different diagnostic groups.

METHODS: The study included the analysis of 126 patients. The patients were divided into five diagnostic groups - Alzheimer's disease, non-Alzheimer's dementia, Movement disorder, Dementia and movement disorder, and Healthy controls. The circulating RNA was isolated using the iCatcher Circulating cfRNA 1000 Kit with the iCatcher 12 automated isolator. The determination of microRNA was performed by TT-qPCR in the CFX96™ Real-Time Detection System. The concentrations of the remaining biomarkers were determined by ELISA. The statistical data were processed using MS Excel and MedCalc® software.

RESULTS: The following miRNAs were studied based on the primary screen for identification of potential microRNA targets and published literature data:hsa-miR-23a-3p, hsa-miR-29c-3p, hsa-miR-30b-5p, hsa-miR-142a-5p, hsa-miR-146a-5p, hsa-miR-151a-3p.A statistically significant correlation was identified between hsa-miR-29c-3p and hsa-miR-30b-5p, hsa-miR-30b-5p and hsa-miR-151a-3p, hsa-miR-23a-3p and hsa-miR-29c-3p, hsa-miR-23a-3p and hsa-miR-151a-3p, between hsa-miR23a-3p and hsa-miR-30b-5p, between hsa-miR-142a-5p and hsa-miR-146a-5p, hsa-miR-142a-5p and hsa-miR-151a-3p as well as between hsa-miR-146a-5p and hsa-miR-151a-3p.Significant differences were observed in hsa-miR-23a-3p and hsa-miR-29c-3p among different diagnostic groups. Compared to classical biomarkers of dementia, significant correlations were observed between plasmatic amyloid-β peptide 42 and hsa-miR-29c-3p, hsa-miR-142a-5p, hsa-miR-146a-5p, hsa-miR-151a-3p. Similar correlations were also found with the plasmatic amyloid-β peptide ratio of 42/40.

CONCLUSIONS: The most promising microRNAs for differentiating among neurodegenerative diseases are hsa-miR-23a-3p and hsa-miR-29c-3p. Additionally, there is a correlation between hsa-miR-29c-3p and amyloid-β peptide and the ratio of amyloid-β peptide 42/40.While more robust studies are necessary, there could be a potential for utilizing this miRNA as a therapeutic agent in the future.},
}

Humans
*MicroRNAs/blood/genetics
Biomarkers/blood
Female
Male
*Neurodegenerative Diseases/diagnosis/genetics/blood
Middle Aged
Aged
Alzheimer Disease/diagnosis/genetics/blood
Case-Control Studies

@article {pmid41071679,
year = {2025},
author = {Bui, V and Santerre, M and Shcherbik, N and Sawaya, BE},
title = {Mitochondria-associated membranes (MAMs): molecular organization, cellular functions, and their role in health and disease.},
journal = {FEBS open bio},
volume = {},
number = {},
pages = {},
doi = {10.1002/2211-5463.70121},
pmid = {41071679},
issn = {2211-5463},
support = {MH093331/MH/NIMH NIH HHS/United States ; NS076402/NS/NINDS NIH HHS/United States ; AG054411/AG/NIA NIH HHS/United States ; },
abstract = {Mitochondria-associated membranes (MAMs) are specialized contact sites between the endoplasmic reticulum (ER) and mitochondria that maintain cellular homeostasis through precisely orchestrated molecular mechanisms. These dynamic interfaces are maintained at 10-50 nm distances by complex tethering proteins, including the core IP3R-GRP7 5-VDAC1 complex and regulatory proteins, such as the sigma-1 receptor. MAMs coordinate multiple essential cellular processes: lipid synthesis and transfer, calcium signaling, metabolic regulation, and quality control through autophagy and mitophagy. Recent advances in super-resolution microscopy and proteomics have revealed that MAM dysfunction drives pathogenesis across various diseases. In Alzheimer's disease, disrupted MAM spacing directly affects Aβ production and mitochondrial function, while in Parkinson's disease, α-synuclein accumulation at MAMs impairs phosphatidylserine metabolism and mitochondrial dynamics. Beyond neurodegeneration, MAMs play crucial roles in metabolic disorders, cancer progression, and viral infections. This review provides mechanistic insights into MAM biology, from molecular organization to disease pathogenesis, integrating structural analyses with dynamic visualization approaches. We examine emerging therapeutic strategies targeting MAM-associated pathways and highlight their potential in treating complex diseases.},
}

@article {pmid41068831,
year = {2025},
author = {Alkhanjari, RR and Alhajeri, MM and Bhamidimarri, PM and Alhosani, K and Kashir, J and Torii, T and Hamdan, H},
title = {Septins in the nervous system: from cytoskeletal dynamics to neurological disorders.},
journal = {Cell communication and signaling : CCS},
volume = {23},
number = {1},
pages = {425},
pmid = {41068831},
issn = {1478-811X},
support = {KU-FSU 8474000395//Khalifa University of Science, Technology and Research/ ; },
abstract = {Septins are GTP-binding cytoskeletal proteins primarily known to be involved in cell division, membrane remodeling, and cytoskeletal organization. In the nervous system, septins are suggested as key regulators of neural development, including neurite outgrowth, spine morphology, and axon initial segment formation. Septins are localized to specialized membrane domains, such as dendritic spines, axon initial segments, and synaptic terminals, where they function as scaffolding components and diffusion barriers. They are abundant in neurons, oligodendrocytes, Schwann cells, and astrocytes, regulating processes like myelination and synaptic organization. In neuronal cells, specific septin isoforms such as SEPT3, SEPT5, and SEPT7 contribute to dendritic spine formation, neurotransmitter vesicle trafficking, and axonal integrity. Alterations in septin expression or assembly can disrupt synaptic architecture and neuroplasticity, emphasizing their role in neuronal homeostasis. Dysregulation of septin expression and function has been implicated in a range of neurological disorders, including demyelinating diseases like Multiple Sclerosis and Hereditary Neuralgic Amyotrophy. Abnormal septin aggregation has been observed in neurodegenerative diseases such as Alzheimer's and Parkinson's disease. Moreover, septins can modulate inflammatory responses, where antibodies for septins 5 and 7 were associated with autoimmune encephalitis conditions. This review will provide a comprehensive overview of the role of septins in the nervous system, focusing on their molecular mechanisms, cellular functions, and implications in neurological disorders.},
}

@article {pmid41037798,
year = {2025},
author = {Park, HJ and Kim, J and Choi, J and Ryou, C and Shin, E and Lee, JY},
title = {Targeted genome editing of ZKSCAN3 mitigates the neurotoxicity caused by mutant HTT (huntingtin) in a Huntington disease animal model and three-dimensional cell culture of Huntington disease.},
journal = {Autophagy},
volume = {},
number = {},
pages = {1-15},
doi = {10.1080/15548627.2025.2569965},
pmid = {41037798},
issn = {1554-8635},
abstract = {Huntington disease (HD) is a neurodegenerative disease caused by the expression of a mutant form of HTT (huntingtin; mHTT), caused by an abnormal expansion of polyglutamine in HTT. In HD, macroautophagy/autophagy dysfunction can cause mHTT accumulation. Moreover, the promotion of autophagy is considered a therapeutic strategy for the treatment of HD. ZKSCAN3 (zinc finger with KRAB And SCAN domains 3) has been identified as a transcriptional repressor of TFEB (transcription factor EB), a master regulator of autophagy and lysosomal functions. In this study, we conducted CRISPR-Cas9-based gene ablation to disrupt ZKSCAN3 in HD animal models and HD patient-induced pluripotent stem cell (iPSC) -derived three-dimensional (3D) spheroids. In animal models of HD, targeted in vivo zkscan3 ablation via a single adeno-associated virus (AAV) mediated CRISPR-Cas9 approach resulted in reduced mHTT levels, leading to improvements in both behavioral symptoms and the brain environment. Furthermore, CRISPR-Cas9 mediated ablation of ZKSCAN3 in 3D spheroids from HD patient-derived iPSC resulted in increased autophagy and lysosomal function, along with reduced mHTT accumulation. Specifically, in iPSC-derived neurons from HD patients, ZKSCAN3-depleted neurons demonstrated increased lysosomal function and reduced oxidative stress compared to controls. Additionally, transcriptional analysis of ZKSCAN3-edited neurons revealed an increased expression of genes involved in synaptic function and transporter activity. Taken together, these results suggest that in HD treatment strategies for improving neuronal function and the brain environment, ZKSCAN3 downregulation in neurons by autophagy activation may improve the brain environment through neuronal self-repair.Abbreviations: 2D: two-dimensional; 3D: three-dimensional; 4-HNE: 4-hydroxynonenal; AAV: adeno-associated virus; AD: Alzheimer disease; Aβ: beta-amyloid; DAPI: 4,6-diamidino-2-phenylindole; GFP: green fluorescent protein; HD: Huntington disease; HTT: huntingtin; IXMC: ImageXpress microconfocal high-content imaging system; Indel: insertion or deletion; iPSC: induced pluripotent stem cell; LAMP1: lysosomal-associated membrane protein 1; mHTT: mutant huntingtin; NPCs: neural precursor cells; RBFOX3/NeuN: RNA binding fox-1 homolog 3; PD: Parkinson disease; RNP: ribonucleoprotein; sgRNAs: single guide RNAs; ST: striatum; TFEB: transcription factor EB; TUBB3/Tuj-1: tubulin beta 3 class III; ZKSCAN3: zinc finger with KRAB and SCAN domains 3.},
}

@article {pmid41071672,
year = {2025},
author = {Aytaç, ÖG and Gündoğdu, HB and Aytaç, S and Bingöl, Z and Gülçin, İ and Kara, Y},
title = {Novel Isoindole-1,3-Dione-Isoxazole Hybrids: Synthesis, Characterization, Evaluation of Their Inhibitory Activities on Carbonic Anhydrase and Acetylcholinesterase.},
journal = {Journal of biochemical and molecular toxicology},
volume = {39},
number = {10},
pages = {e70550},
doi = {10.1002/jbt.70550},
pmid = {41071672},
issn = {1099-0461},
support = {//The authors are appreciative to Department of Chemistry and Atatürk University for financial support./ ; },
mesh = {*Carbonic Anhydrase Inhibitors/chemical synthesis/chemistry/pharmacology ; *Acetylcholinesterase/chemistry/metabolism ; *Cholinesterase Inhibitors/chemical synthesis/chemistry/pharmacology ; Humans ; Molecular Docking Simulation ; *Carbonic Anhydrase II/chemistry/antagonists & inhibitors ; *Carbonic Anhydrase I/chemistry/antagonists & inhibitors/metabolism ; *Isoxazoles/chemistry/chemical synthesis/pharmacology ; *Isoindoles/chemistry/chemical synthesis/pharmacology ; GPI-Linked Proteins ; },
abstract = {It is known that compounds containing isoxazole units exhibit a high potential for biological activity due to the isoxazole ring. In this study, eight hexahydro-5H-isoxazolo[4,5-f]isoindole-5,7(6H)-dione derivatives bearing isoxazole moieties were synthesized and their inhibitory effects on various metabolic enzymes, including acetylcholinesterase (AChE) and human carbonic anhydrase isoforms I and II (hCA I and hCA II), which are associated with global disorders such as Alzheimer's disease (AD), epilepsy, and glaucoma, were investigated. Among the synthesized compounds, derivatives 9-12 exhibited notable inhibitory activity against AChE, hCA I, and hCA II enzymes. The IC50 values were determined to be in the ranges of 4.65-12.83 nM for AChE, 23.17-79.58 nM for hCA I, and 36.58-88.28 nM for hCA II. Molecular docking studies of the synthesized compounds 9a-12a were carried out against three proteins: 1AZM (Human carbonic anhydrase I), 5AML (three-dimensional structure of human carbonic anhydrase II) and 4EY6 (recombinant human acetylcholinesterase). AZA and Tacrine were used as references in the docking analyses. All compounds were determined to have a higher binding affinity than Tacrine (-7.04 kcal/mol) and AZA (-6.12 and -6.24 kcal/mol). The results of inhibition tests showed that some isoxazole derivatives (9-12) showed significant inhibitory effects against both CA and AChE enzymes.},
}

*Carbonic Anhydrase Inhibitors/chemical synthesis/chemistry/pharmacology
*Acetylcholinesterase/chemistry/metabolism
*Cholinesterase Inhibitors/chemical synthesis/chemistry/pharmacology
Humans
Molecular Docking Simulation
*Carbonic Anhydrase II/chemistry/antagonists & inhibitors
*Carbonic Anhydrase I/chemistry/antagonists & inhibitors/metabolism
*Isoxazoles/chemistry/chemical synthesis/pharmacology
*Isoindoles/chemistry/chemical synthesis/pharmacology
GPI-Linked Proteins