Frontiers in Aging Neuroscience最新文献

{"title":"Complement C4b and factor B in astrocyte-derived exosomes as novel biomarkers for amnestic mild cognitive impairment.","authors":"Yu Li, Menglu Zhang, Chao Ying, Chao Han, Qimeng Li, Yanning Cai","doi":"10.3389/fnagi.2026.1727449","DOIUrl":"https://doi.org/10.3389/fnagi.2026.1727449","url":null,"abstract":"<p><p>Neuroinflammation represents a fundamental pathological mechanism underlying amnestic mild cognitive impairment (aMCI), with dysregulated activation of the complement system playing a pivotal role. Astrocyte-derived exosomes (ADEs), which are capable of traversing the blood-brain barrier (BBB), offer a non-invasive means to investigate central nervous system pathology. This study explored the diagnostic potential of two principal complement components, C4b and factor B (FB), within plasma-derived ADEs for aMCI and analyzed their interaction with the <i>ApoE</i> ε4 allele. We enrolled 99 aMCI patients and 96 demographically matched normal controls (NC). C4b and FB levels in plasma-derived ADEs were quantified using ELISA, and all participants underwent <i>ApoE</i> genotyping. In the total cohort, levels of both C4b and FB in ADEs were significantly elevated in the aMCI group compared to NC. Diagnostic model validation demonstrated that adding C4b alone or in combination with FB to a baseline model significantly improved diagnostic performance, whereas adding FB alone provided no significant benefit. Notably, the <i>ApoE</i> ε4 genotype exerted a precise modulatory effect: among <i>ApoE</i> ε4 non-carriers, C4b levels were elevated in the aMCI group but did not yield significant diagnostic improvement; in contrast, among <i>ApoE</i> ε4 carriers, both C4b and FB were specifically upregulated, and only their combination achieved excellent diagnostic performance (AUC = 0.833; DeLong's test, <i>P</i> = 0.017), whereas neither marker alone was effective. Furthermore, C4b exhibited broader and more significant correlations with cognitive function compared to FB. This study substantiates that ADE-derived C4b serves as a reliable diagnostic biomarker for aMCI, whereas the diagnostic efficacy of FB is contingent upon <i>ApoE</i> ε4 allele status. Consequently, we propose a precision diagnostic strategy that involves the concurrent assessment of C4b and FB specifically in individuals carrying the <i>ApoE</i> ε4 allele, thereby presenting a novel approach for the early detection of aMCI.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"18 ","pages":"1727449"},"PeriodicalIF":5.2,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13661567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149192645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electroacupuncture inhibits pyroptosis to improve motor function in an MPTP-induced mouse model of Parkinson's disease.","authors":"Yu-Chen Ying, Yi-Yue Dong, Guang-Yan Chen, Xi Wang, Qian Fan, Xi-Chen Wu, Yue-Lai Chen","doi":"10.3389/fnagi.2026.1968826","DOIUrl":"10.3389/fnagi.2026.1968826","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate whether electroacupuncture (EA) ameliorates motor dysfunction and protects nigrostriatal dopaminergic neurons in Parkinson's disease (PD) mice by inhibiting NLRP3 inflammasome-mediated pyroptosis.</p><p><strong>Methods: </strong>Male C57BL/6 mice were randomly assigned before model induction to seven groups: saline-treated control, MPTP model, MPTP plus EA, MPTP plus Nigericin, MPTP plus EA and Nigericin, MPTP plus MCC950, and MPTP plus EA and MCC950 groups. Mice in the control group received equal-volume saline, whereas mice in the other six groups were administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 30 mg/kg, intraperitoneally) once daily for five consecutive days. Following model induction, EA was applied at Baihui (GV20) and Dazhui (GV14) at 100 Hz for 20 min per session over 14 days. Nigericin and MCC950 were used as an NLRP3 inflammasome activator and inhibitor, respectively. Motor function was assessed using the open-field and pole tests. Dopaminergic neuronal integrity, neuronal injury, microglial activation, and the cellular localization of NLRP3 were evaluated using immunohistochemistry, hematoxylin-eosin staining, and immunofluorescence. The expression levels of tyrosine hydroxylase, NLRP3, ASC, Caspase-1, and the N-terminal fragment of gasdermin D (GSDMD-N) were determined using immunofluorescence and western blotting.</p><p><strong>Results: </strong>EA alleviated abnormal open-field hyperlocomotion and prolonged pole-descent latency in MPTP-treated mice, preserved tyrosine hydroxylase-positive dopaminergic neurons in the substantia nigra, restored striatal tyrosine hydroxylase expression, and reduced neuronal injury and microglial activation. NLRP3 was predominantly colocalized with tyrosine hydroxylase-positive dopaminergic neurons, whereas limited colocalization was observed with IBA-1-positive microglia. Electroacupuncture significantly suppressed the MPTP-induced upregulation of NLRP3, ASC, Caspase-1, and GSDMD-N. Nigericin exacerbated motor abnormalities, nigrostriatal injury, and pyroptosis-related signaling and largely abolished the protective effects of EA. Conversely, MCC950 produced protective effects comparable to those of EA, whereas their combined administration provided no significant additional benefit.</p><p><strong>Conclusion: </strong>EA improves motor dysfunction and protects the nigrostriatal dopaminergic system in MPTP-induced PD mice, at least partly by suppressing NLRP3 inflammasome-mediated pyroptosis in dopaminergic neurons. These findings identify the NLRP3 inflammasome as an important mechanistic target underlying the neuroprotective effects of electroacupuncture in experimental PD.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"18 ","pages":"1968826"},"PeriodicalIF":5.2,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13661978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Self-reported chewing or swallowing problems and episodic memory performance in older Americans: a longitudinal cohort study.","authors":"Fei He, Chonghao Yao, Xuteng Kang, Yihao Ding, Haoqi Tu, Sijia Na","doi":"10.3389/fnagi.2026.1899130","DOIUrl":"10.3389/fnagi.2026.1899130","url":null,"abstract":"<p><strong>Background: </strong>Impaired mastication is a plausible modifiable risk factor for dementia, but long-term longitudinal evidence using functional metrics instead of tooth counts is limited. This study investigated the association between self-reported chewing/swallowing problems and cognitive decline trajectories in older adults.</p><p><strong>Methods: </strong>We analyzed repeated NHATS rounds 7-14. The primary analytic sample comprised 8,636 participants contributing 34,571 person-round observations with valid exposure and immediate plus delayed 10-word recall. Raw total recall (0-20) was the primary outcome. Linear mixed models used rounds since each participant's first complete analytic assessment, time-varying exposure, random intercepts and random slopes, and adjustment for age, sex, race/ethnicity, education, comorbidity count, depressive symptoms, hearing impairment, and vision impairment.</p><p><strong>Results: </strong>At the first complete analytic assessment, 842 participants (9.7%) reported chewing or swallowing problems. In the primary model, the exposure-by-time interaction was -0.035 recall points per follow-up round (95% CI, -0.075 to 0.005; <i>p</i> = 0.086). The contemporaneous exposure coefficient at follow-up round 0 was 0.034 points (95% CI, -0.106 to 0.173; <i>p</i> = 0.638). Results were similar when participants with one assessment were excluded and when the outcome was modeled as immediate recall, delayed recall, or standardized against a common reference.</p><p><strong>Conclusion: </strong>In this analytic NHATS sample, self-reported chewing or swallowing problems were not independently associated with a statistically significant difference in episodic-memory trajectory after sensory and other prespecified adjustment. The item may warrant oral, swallowing, functional, or neurological assessment, but it is not a specific marker of masticatory dysfunction or cognitive risk.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"18 ","pages":"1899130"},"PeriodicalIF":5.2,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13661535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carotid atherosclerosis progression in patients with Parkinson's disease: a prospective cohort study.","authors":"Siyu Wang, Ni Yang, Haoyang Cheng, Qingbo Zhou","doi":"10.3389/fnagi.2026.1928073","DOIUrl":"https://doi.org/10.3389/fnagi.2026.1928073","url":null,"abstract":"<p><strong>Background: </strong>Evidence regarding the association between Parkinson's disease (PD) and cardio-cerebrovascular risk remains conflicting, and it is unclear whether the dynamic progression of carotid atherosclerosis in PD patients differs from that in non-PD individuals. This study aimed to compare the progression of carotid atherosclerosis over a 1-year follow-up between PD patients and matched controls, and to investigate whether PD influences this progression independently of traditional cardiovascular risk factors.</p><p><strong>Methods: </strong>This prospective cohort study ultimately included 61 PD patients and 59 age- and sex-matched non-PD controls. Carotid ultrasound was performed at baseline and at the 1-year follow-up. The primary outcome was the annual change in total plaque area (ΔTPA), with plaque progression defined as ΔTPA ≥ 0.05 cm². Multivariable logistic regression models, adjusting for diabetes, smoking, total cholesterol, and low-density lipoprotein cholesterol (LDL-C), were used to assess the independent association between PD status and plaque progression.</p><p><strong>Results: </strong>At baseline, carotid intima-media thickness and TPA were significantly lower in the PD group than in the control group (both <i>P</i> < 0.05). After 1 year, ΔTPA was significantly smaller in the PD group (<i>P</i> < 0.001), and the incidence of plaque progression was 6.56% in PD patients versus 25.42% in controls. Multivariable regression analysis showed that PD status was a protective factor against atherosclerosis progression (adjusted OR = 0.27, 95% CI: 0.074-0.984, <i>P</i> = 0.047). Within the PD group, no significant associations were observed between plaque progression and disease-specific factors such as disease duration, motor severity, or levodopa equivalent daily dose.</p><p><strong>Conclusion: </strong>Carotid atherosclerosis progression is significantly slower in PD patients than in non-PD individuals, and this effect is independent of traditional cardiovascular risk factors. These findings suggest that PD patients may exhibit a \"vascular protective phenotype,\" and that a unique shared regulatory network may exist between neurodegenerative processes and peripheral vascular homeostasis.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"18 ","pages":"1928073"},"PeriodicalIF":5.2,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149192615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multicomponent training versus elastic-band training for improving global cognition and executive function in older women: a randomized controlled trial.","authors":"Edgar Vásquez-Carrasco, Pablo Aravena-Sagardia, Mauricio Barramuño-Medina, Sebastián Valenzuela-Rosel, Victor Alarcón-Zambrano, Jordan Hernandez-Martinez, Roberto López-Andaur, Cristian Sandoval-Vásquez, Braulio Henrique Magnani Branco, Pablo Valdés-Badilla","doi":"10.3389/fnagi.2026.1911384","DOIUrl":"https://doi.org/10.3389/fnagi.2026.1911384","url":null,"abstract":"<p><strong>Objective: </strong>To compare the effects of multicomponent training (MCT) and elastic-band training (EBT) on global cognition and executive function in older women.</p><p><strong>Methods: </strong>This single-blind, parallel-group randomized controlled trial was conducted over 16 weeks and included two supervised 60-min sessions per week. Twenty-six older women were randomly assigned to either the MCT group (<i>n</i> = 13) or the EBT group (<i>n</i> = 13). Cognitive outcomes included global cognition assessed with the Montreal Cognitive Assessment (MoCA), processing speed and visual attention assessed with the Trail Making Test Part A (TMT-A), and executive function assessed with the Trail Making Test Part B (TMT-B). Linear mixed-effects models were used to evaluate group, time, and group × time effects while adjusting for age and education. TMT-B was predefined as the primary executive function outcome.</p><p><strong>Results: </strong>A significant group × time interaction was observed for TMT-B performance (<i>p</i> = 0.019). However, neither the within-group nor between-group <i>post hoc</i> comparisons remained significant after false discovery rate (FDR) correction, and the interaction did not remain significant when FDR correction was conservatively applied across all model-level interactions. No significant group × time interactions were observed for MoCA (<i>p</i> = 0.289) or TMT-A (<i>p</i> = 0.214).</p><p><strong>Conclusion: </strong>Although the primary model suggested different temporal trajectories in TMT-B performance, the nonsignificant adjusted <i>post hoc</i> comparisons and the conservative sensitivity analysis preclude any conclusion that MCT was superior to EBT. Neither intervention produced significant changes in global cognitive performance or processing speed and visual attention. Therefore, the TMT-B finding should be considered exploratory and requires confirmation in larger, adequately powered randomized controlled trials.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"18 ","pages":"1911384"},"PeriodicalIF":5.2,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149192670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resting-state cortical alpha frequency in Parkinson's disease and multiple system atrophy: associations with diagnosis, age, and symptom burden.","authors":"Daichao Chen, Huada Tang, Yanfei Pan, Hui Sang, Saiya Gu, Xinpeng Wang, Kai Li, Fan Li, Yunchuang Sun, Jing Chen, Wei Sun, Jue Zhang, Zhaoxia Wang, Luhua Wei","doi":"10.3389/fnagi.2026.1928414","DOIUrl":"10.3389/fnagi.2026.1928414","url":null,"abstract":"<p><strong>Background: </strong>Parkinson's disease (PD) and multiple system atrophy (MSA) are clinically overlapping neurodegenerative disorders that present with a complex, heterogeneous burden of motor and non-motor symptoms. Resting-state EEG reveals that cortical alpha slowing is a hallmark of pathological aging, yet its specific presence and clinical significance in these distinct synucleinopathies remain incompletely understood. Therefore, precisely quantifying the individual alpha frequency serves as a critical, non-invasive approach to characterize cortical network dysfunction across synucleinopathies and evaluate how aging moderates its association with clinical symptom burden.</p><p><strong>Methods: </strong>We analyzed source-reconstructed resting-state EEG data from 104 participants, comprising patients with PD, patients with the parkinsonian (MSA-P) and cerebellar subtypes (MSA-C) of MSA, and healthy controls. To accurately capture oscillatory dynamics, a data-driven masking empirical mode decomposition approach was applied to extract the individual alpha frequency across canonical cortical networks. General linear models tested diagnostic group differences, age-related effects, and age-dependent associations between individual alpha frequency and clinical symptom scores.</p><p><strong>Results: </strong>Relative to healthy controls, both PD and MSA-C exhibited significant lower cortical IAF, whereas MSA-P showed no significant global IAF difference. At the network level, significant reduction of IAF was detected in the visual and dorsal attention networks in both PD and MSA-C. Advancing age independently contributed to alpha slowing across all participants without accelerating the disease-related trajectories. Notably, chronological age significantly moderated the relationship between alpha slowing and non-motor symptoms. In older patients, reduced individual alpha frequency was strongly associated with a higher burden of overall non-motor, autonomic, and psychiatric/cognitive symptoms, a relationship not observed in younger patients or with motor symptom severity.</p><p><strong>Conclusion: </strong>Cortical alpha slowing was detected in PD and MSA-C, but not in MSA-P. Age independently contributes to alpha slowing and strengthens its association with non-motor symptom burden, supporting age-aware interpretation of resting-state electroencephalography biomarkers in synucleinopathies.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"18 ","pages":"1928414"},"PeriodicalIF":5.2,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13661991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clemastine alleviates Parkinson's disease pathology by activating the AMPK/mTOR pathway and enhancing autophagic flux.","authors":"Ting Fan, Caihui Wei, Wenzhi Chen, Shu Li, Junling Wang, Yi Lu, Renshi Xu","doi":"10.3389/fnagi.2026.1915475","DOIUrl":"https://doi.org/10.3389/fnagi.2026.1915475","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a debilitating neurodegenerative disorder with no available cure, underscoring the urgent need for novel therapeutics. This study employed the comprehensive bioinformatic analyses and the experimental models to investigate the potential of clemastine (CLE) for PD treatment. Bioinformatics identified 12 distinct cell subtypes and 577 differentially expressed genes in dopaminergic neurons (DaNs), along with 167 potential PD-relevant CLE targets. A significant correlation was found between Braak stage and autophagy-related gene expression in the substantia nigra. In MPP⁺-induced PC12 cell model, CLE treatment increased AMPK phosphorylation and decreased mTOR phosphorylation at Ser2448, suggesting the activation of AMPK and reduced mTOR activity, which was accompanied by the reduced levels of α-synuclein (α-syn) and p62, increased lysosomal (LAMP1) and autophagosomal (LC3) markers, and enhanced cell viability. CLE increased the LC3-II/LC3-I ratio even in the presence of bafilomycin A1, indicating enhanced autophagosome synthesis. Conversely, the AMPK inhibitor dorsomorphin blocked CLE effects, restoring mTOR phosphorylation and α-syn levels. In the chronic MPTP-induced mouse model, CLE administration increased the phosphorylation of AMPK, increased the LC3-II/LC3-I ratio, and decreased mTOR phosphorylation, p62, and α-syn levels. Immunofluorescence revealed the increased DaNs (tyrosine hydroxylase-positive) and LC3 puncta, alongside reduced the phosphorylated α-syn (p-S129). These cellular and molecular improvements correlated with the alleviation of both motor (rotarod test) and non-motor (fecal pellet output) deficits. Collectively, our findings suggest that CLE alleviates PD pathology by increasing AMPK phosphorylation and decreasing mTOR phosphorylation at Ser2448, suggesting the activation of AMPK pathway and reduced mTOR activity, thereby enhancing the autophagic flux by promoting both the synthesis and degradation of autophagosomes. Subsequently it facilitates the clearance of pathological α-syn, improves the neuronal survival, and ameliorates the behavioral symptoms. We propose CLE as a promising therapeutic candidate for PD via autophagy modulation.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"18 ","pages":"1915475"},"PeriodicalIF":5.2,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global research trends and hotspots in blood-based biomarkers for Alzheimer's disease: a bibliometric analysis.","authors":"Shengjie Wang, Junyao Zhang, Shaojun Sun, Renlong Xiao, Zhiyi Zhang, Junyan Yao","doi":"10.3389/fnagi.2026.1886781","DOIUrl":"https://doi.org/10.3389/fnagi.2026.1886781","url":null,"abstract":"<p><strong>Background: </strong>Blood-based biomarkers (BBMs) are rapidly reshaping the diagnostic and translational landscape of Alzheimer's disease (AD), offering a scalable alternative to cerebrospinal fluid (CSF) assays and positron emission tomography (PET). This paper aims to conduct bibliometric analysis on the hotspots and trends in this field.</p><p><strong>Methods: </strong>Publications addressing AD-related blood/plasma/serum biomarkers from 1 January 2011 to 29 November 2025 were retrieved from the Web of Science Core Collection (WoSCC) and Scopus. Only English-language articles and reviews were included. VOSviewer, CiteSpace, and the R package bibliometrix were used to evaluate publication trends, collaboration networks (countries, institutions, authors), co-cited journals and references, and keyword evolution.</p><p><strong>Results: </strong>A total of 1,771 publications with 53,568 citations were included. Annual output rose steadily and accelerated after 2018, while 2025 records covered approximately the first 11 months of the year. The USA (795 publications) and China (478) were the most productive countries, whereas the UK and Sweden showed strong citation impact and collaboration intensity. The University of Gothenburg (263) and Sahlgrenska University Hospital (237) were the leading institutions. Henrik Zetterberg (218) and Kaj Blennow (185) were the most prolific authors. Co-citation analysis identified the NIA-AA biological research framework and validation studies of plasma amyloid-beta (Aβ) and plasma phosphorylated tau (p-tau) as the intellectual base. Keyword and burst analyses indicated a clear shift from early themes (e.g., proteomics and oxidative stress) toward clinically oriented topics, including plasma p-tau217/p-tau181, diagnostic performance, and implementation recommendations.</p><p><strong>Conclusion: </strong>Research on AD BBMs has entered a phase of rapid growth and clinical translation. Plasma phosphorylated tau (especially p-tau217) is the leading biomarker for detecting AD-specific pathology. Plasma Aβ ratios play a supportive role in amyloid triage, while neurodegeneration (NfL) and astroglial (GFAP) markers provide complementary information for prognosis and monitoring. Future priorities include real-world implementation, assay standardization, and integration of multi-marker panels into biological diagnostic/staging frameworks.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"18 ","pages":"1886781"},"PeriodicalIF":5.2,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13659226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-related differences in behavioral and brain predictors of parkinsonism in autistic adults.","authors":"Manuela Velez Galindo, Goldie A McQuaid, Rebecca A Charlton, Edward Ofori, Daniel S Peterson, David Q Beversdorf, Melony Valdez, Anthony C Rodi, Abdullah Sabri, Julia Smith-Plata, Hector Cervantes, Gregory L Wallace, B Blair Braden","doi":"10.3389/fnagi.2026.1893104","DOIUrl":"10.3389/fnagi.2026.1893104","url":null,"abstract":"<p><p>Autistic adults experience lifelong motor differences and may have increased vulnerability to parkinsonism, yet behavioral and neuroanatomical correlates of motor challenges across adulthood remain poorly understood. We examined cross-sectional behavioral and motor-related brain region morphology in autistic (<i>n</i> = 123) and non-autistic (<i>n</i> = 102) adults aged 18-71 years using the Parkinsonism Screening Questionnaire (PSQ), Adult Repetitive Behavior Questionnaire-2 (RBQ-2A), finger tapping, and MRI-derived cortical thickness and subcortical volumes of motor-related brain regions. Replication of the questionnaire analyses was conducted in an independent cohort of middle- and older-aged autistic adults from the Simons Powering Autism Research (SPARK; <i>n</i> = 210; ages 42-80 years), whereas structural MRI and finger tapping analyses were limited to the Arizona cohort. Autistic adults reported significantly higher PSQ scores than non-autistic adults. A significant group-by-age interaction was observed for RBQ-2A Factor 1, with autistic adults showing a steeper age-related reduction in repetitive motor and sensory behaviors. RBQ-2A scores were positively correlated with PSQ scores across both cohorts. Finger tapping performance did not differ between groups. Caudate volumes were larger in autistic adults and showed a modestly stronger negative association with age that did not survive multiple comparison correction. These findings suggest that self-reported restricted, repetitive motor behaviors and interests may serve as an indicator of self-reported parkinsonism-like symptoms in autism and highlight the need for longitudinal studies to clarify mechanisms of parkinsonism risk across the lifespan.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"18 ","pages":"1893104"},"PeriodicalIF":5.2,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multimodal neuroimaging and electrophysiological signatures in amnestic mild cognitive impairment with different amyloid-β deposition status: correlations with cognitive function and diagnostic value.","authors":"Yang Liang, Peixue Li, Lin Liu, Chunbo Dong, Xiaohong Wang","doi":"10.3389/fnagi.2026.1896908","DOIUrl":"https://doi.org/10.3389/fnagi.2026.1896908","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Amnestic mild cognitive impairment (aMCI) is a heterogeneous transitional cognitive state between normal aging and dementia. Aβ positivity elevates dementia conversion risk but does not equate to prodromal Alzheimer's disease (AD), and not all Aβ-positive aMCI individuals progress to clinical AD dementia. Distinguishing Aβ-positive from Aβ-negative aMCI facilitates pathological subtyping rather than definitive early AD diagnosis. This cross-sectional study aimed to characterize scalp-level resting-state EEG and structural MRI signatures specific to Aβ-positive aMCI, explore their covariate-adjusted correlations with cognitive performance and regional Aβ burden, and develop an internally validated multimodal auxiliary classification model for Aβ stratification.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Fifty enrolled aMCI participants (30 Aβ-positive, 20 Aβ-negative) and 35 cognitively normal controls (NC) completed unified 20-min eyes-closed resting-state scalp EEG, 3.0 T structural MRI, &lt;sup&gt;18&lt;/sup&gt;F-AV45 amyloid PET and &lt;sup&gt;18&lt;/sup&gt;F-FDG cerebral metabolism PET examinations. Artifact-free scalp EEG spectral power and regional θ/α ratio were calculated via Welch spectral analysis; voxel-based morphometry (VBM) was adopted to quantify whole-brain gray matter volume. Covariate-controlled partial correlation corrected for multiple comparisons was applied to evaluate cross-modal associations among cortical Aβ SUVR load, cerebral glucose metabolism and domain-specific cognitive scores. A binary logistic regression classification model combining screened EEG and MRI markers was established, with DeLong test for ROC curve comparison and 1,000-bootstrap internal validation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;(1) Relative to Aβ-negative aMCI and NC groups, the Aβ-positive subgroup presented significantly elevated whole-scalp θ relative power and scalp θ/α ratio, decreased scalp α and β relative power (all &lt;i&gt;q&lt;/i&gt; &lt; 0.05, FDR-corrected), with predominant scalp oscillatory alterations distributed over temporal, parietal and occipital scalp electrode clusters. The temporal scalp θ/α ratio yielded optimal classification performance for Aβ stratification (AUC = 0.875). (2) The Aβ-positive subgroup showed significant gray matter atrophy across 13 AD-vulnerable brain regions including bilateral fusiform gyrus, inferior parietal lobule, parahippocampal gyrus, precuneus and right entorhinal cortex (all &lt;i&gt;q&lt;/i&gt; &lt; 0.05), with the maximum effect size identified in the right precuneus (partial &lt;i&gt;η&lt;/i&gt; &lt;sup&gt;2&lt;/sup&gt; = 0.477, AUC = 0.778). (3) Within the Aβ-positive subgroup, the temporal scalp θ/α ratio was positively correlated with medial temporal Aβ SUVR (&lt;i&gt;r&lt;/i&gt; = 0.501, 95% CI [0.146, 0.732], &lt;i&gt;q&lt;/i&gt; = 0.030); right precuneus gray matter volume was negatively correlated with multi-region cortical Aβ burden (&lt;i&gt;q&lt;/i&gt; &lt; 0.05). Left parahippocampal gyrus volume was positively correlated with MoCA memory subscores (&lt;i&gt;r&lt;/i&gt; = 0.479, 95% CI [0","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"18 ","pages":"1896908"},"PeriodicalIF":5.2,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}