Frontiers in Aging Neuroscience最新文献

{"title":"Research progress on the role of exercise-regulated reactive astrocytes in the prevention and treatment of Parkinson's disease.","authors":"Quan Yang, Chunyu Zhuang","doi":"10.3389/fnagi.2025.1561006","DOIUrl":"https://doi.org/10.3389/fnagi.2025.1561006","url":null,"abstract":"<p><p>Astrocytes generally perform protective roles, such as the release of neurotrophic factors, glutamate metabolism, transfer of healthy mitochondria to neurons, and maintenance of the blood-brain barrier. Nonetheless, in the context of Parkinson's disease (PD), astrocytes may become dysfunctional, contributing to neurotoxicity, which is intricately linked to the etiological factors of PD. Intervening to prevent the conversion of astrocytes into neurotoxic phenotypes has demonstrated neuroprotective effects, potentially averting the degeneration of dopaminergic neurons and mitigating behavioral deficits in PD model mice. Research has shown that exercise decreases the prevalence of central pro-inflammatory and neurotoxic reactive astrocytes while increasing the presence of anti-inflammatory and neuroprotective reactive astrocytes. Various forms of exercise therapy are extensively employed as adjunctive treatments alongside pharmacotherapy in PD patients, and have been empirically validated to directly enhance motor function, functional flexibility, gait, balance, fine motor skills, and overall quality of life in individuals with PD. The potential mechanism of various types of exercise therapy in improving PD-related behavioral dysfunction is closely related to the regulation of the conversion of pro-inflammatory and neurotoxic reactive astrocytes to anti-inflammatory and neuroprotective astrocytes by exercise. This paper discusses the regulatory role of reactive astrocytes in neuroinflammation and PD neurodegeneration, as well as the reduction of neuroinflammation and the progression of PD through exercise regulation of reactive astrocytes, so as to provide a theoretical basis for further exploring the pathogenesis of PD and further developing therapeutic interventions for neurodegenerative diseases.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1561006"},"PeriodicalIF":4.1,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332771","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":"Functional brain changes in vascular cognitive impairment: a whole brain ALE meta-analysis.","authors":"Chunyang Zhang, Mingchen Xue, Han Zhang, Juan Li, Mingli He","doi":"10.3389/fnagi.2025.1521457","DOIUrl":"https://doi.org/10.3389/fnagi.2025.1521457","url":null,"abstract":"<p><strong>Background: </strong>Vascular cognitive impairment (VCI) is a prevalent form of cognitive dysfunction. Resting-state functional magnetic resonance imaging (rs-fMRI) could serve as a potential biomarker for early detection. This study employed activation likelihood estimation (ALE) meta-analysis to investigate specific neural abnormalities in VCI patients.</p><p><strong>Methods: </strong>We systematically searched PubMed, Embase, and Web of Science for rs-fMRI studies on VCI that reported amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), or functional connectivity (FC). Sixteen eligible fMRI studies were included in the ALE meta-analysis.</p><p><strong>Results: </strong>Compared to healthy controls (HCs), VCI patients exhibited the following rs-fMRI alterations. For ALFF, there was an increase in the left anterior cingulate (AC) and left inferior frontal gyrus, possibly a compensatory over - activation. Decreases were seen in regions like the bilateral precuneus and medial frontal gyri (mFG), linked to cognitive deficits. ReHo increased in the left claustrum and insula, suggesting enhanced local synchronization, but decreased in the right sub - gyral region and middle temporal gyru (MTG), which may relate to language issues. FC was enhanced in areas related to complex cognitive processes, yet reduced in regions crucial for memory.</p><p><strong>Conclusion: </strong>VCI patients exhibited distinct functional abnormalities in specific brain regions, reflecting their diverse cognitive impairments. These region-specific alterations may serve as potential biomarkers for early diagnosis and targeted intervention in VCI.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1521457"},"PeriodicalIF":4.1,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332770","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":"The aging self: how older men and women reflect on themselves and others.","authors":"Marta Paź, Anna Nowicka","doi":"10.3389/fnagi.2025.1600029","DOIUrl":"https://doi.org/10.3389/fnagi.2025.1600029","url":null,"abstract":"","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1600029"},"PeriodicalIF":4.1,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332772","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":"Non-linear relationship between calf circumference and global cognition in Chinese population: a cross-sectional study of 12,102 Chinese older adults.","authors":"Yuting Nie, Cheng Gu, Ruipeng Wu, Fulin Gao, Le Zhang, Yamin Zhang","doi":"10.3389/fnagi.2025.1473135","DOIUrl":"10.3389/fnagi.2025.1473135","url":null,"abstract":"<p><strong>Background: </strong>Limited evidence exists regarding the relationship between calf circumference (CC) and global cognition in the Chinese population, with minimal research exploring potential sex disparities. Our goal was to investigate the correlation between CC and global cognition using data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), focusing specifically on sex variations.</p><p><strong>Methods: </strong>The study participants were older adults who participated in the 2018 CLHLS survey. In this cross-sectional study, we employed multiple linear regression to examine the association between CC and global cognition. Smoothed curve fitting was used to explore the non-linear association between CC and global cognition. Furthermore, subgroup analyses were conducted to evaluate the reliability of the correlation between CC and global cognitive performance.</p><p><strong>Results: </strong>In total, 12,102 older adults were included in the study. A positive correlation was found between global cognition and CC (β = 0.42, 95% CI = 0.3-0.54, <i>P</i> < 0.001) after controlling for confounding factors. Further analysis revealed a non-linear relationship between CC and global cognitive performance. In the overall population, the inflection point for CC was 31 cm; a positive relationship was observed between CC and global cognition for CC values <31 cm (β = 0.177, 95% CI = 0.128-0.225, <i>P</i> < 0.001); however, this relationship disappeared for CC values ≥ 31 cm (β: -0.009, 95% CI = -0.04 to 0.023, <i>P</i> = 0.591). Furthermore, we identified sex-specific variations in the correlation between global cognitive performance and CC. Notably, among women with CC values <32 cm, a significant positive correlation was observed between CC and overall cognitive function. Conversely, for women with CC ≥ 32 cm, no significant association was found between CC and cognitive performance. Interestingly, no non-linear relationship was detected in males.</p><p><strong>Conclusion: </strong>This study demonstrated a non-linear relationship between CC and global cognition in older Chinese population. Furthermore, sex disparities are observed in the relationship between CC and global cognition, with a non-linear link evident in women but not in men. Older women with lower CC should actively participate in physical activity to maintain an appropriate CC and prevent cognitive decline.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1473135"},"PeriodicalIF":4.1,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12174059/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324937","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":"Distinct trajectory patterns of neutrophil-to-albumin ratio predict clinical outcomes after endovascular therapy in large vessel occlusion stroke.","authors":"Weiwei Gao, Junxuan Sun, Lingfeng Yu, Jingjing She, Yanan Zhao, Lijuan Cai, Xingyu Chen, Renjing Zhu","doi":"10.3389/fnagi.2025.1570662","DOIUrl":"10.3389/fnagi.2025.1570662","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the dynamic characteristics and prognostic value of neutrophil-to-albumin ratio (NAR) in patients with acute large vessel occlusion ischemic stroke (LVO-AIS) undergoing endovascular therapy (EVT).</p><p><strong>Methods: </strong>In this retrospective cohort study, we consecutively enrolled 299 patients with anterior circulation LVO-AIS who underwent EVT between January 2018 and February 2024. NAR was measured at admission, day 1, and day 3 after EVT. The primary outcome was poor functional outcome at 90 days (modified Rankin Scale score 3-6). Secondary outcomes included symptomatic intracranial hemorrhage (sICH), malignant cerebral edema (MCE), and in-hospital mortality (IHM). Multivariable logistic regression and restricted cubic spline regression were used to analyze the association between NAR and functional outcomes. Latent class trajectory modeling (LCTM) was applied to identify NAR evolution patterns, and propensity score matching (PSM) was performed to balance baseline characteristics between different trajectory groups, followed by conditional logistic regression to assess their association with clinical outcomes.</p><p><strong>Results: </strong>At 90-day follow-up, 197 patients (65.9%) had poor outcomes. The predictive value of NAR increased over time, with day 3 NAR showing the best predictive performance (poor outcome: AUC = 0.79; sICH: AUC = 0.70; MCE: AUC = 0.75; IHM: AUC = 0.81). Multivariable analysis showed that for each unit increase in day 3 NAR, the risk of 90-day poor outcome increased 2.81-fold (95% CI: 1.96-4.03, <i>p</i> < 0.001). LCTM analysis identified two distinct NAR evolution patterns: continuously increasing (31.1%) and peak-then-decline (68.7%). After PSM (63 patients per group), compared with the continuously increasing trajectory, the peak-then-decline trajectory was associated with significantly lower risks of poor functional outcome (OR = 0.38, 95% CI: 0.17-0.86, <i>p</i> = 0.020), sICH (OR = 0.38, 95% CI: 0.17-0.86, p = 0.020), MCE (OR = 0.25, 95% CI: 0.10-0.61, <i>p</i> = 0.002), and IHM (OR = 0.13, 95% CI: 0.04-0.42, <i>p</i> < 0.001).</p><p><strong>Conclusion: </strong>NAR trajectory patterns independently predict clinical outcomes after EVT for LVO-AIS. Dynamic monitoring of NAR, particularly on day 3 post-procedure, may facilitate early risk stratification and development of targeted intervention strategies, providing a new biomarker tool for precision stroke management.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1570662"},"PeriodicalIF":4.1,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12174067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324924","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":"Interventions for cognitive frailty: developing a Delphi consensus with multidisciplinary and multisectoral experts.","authors":"Carol A Holland, Nikolett Dravecz, Susan Broughton, Lynne A Barker, Fidelia Bature, Charlotte Clarke, Isaac M Danat, Sayani Das, Irundika H K Dias, Annabel Dawson, M Dixon, Amanda Ellison, David Façal, Roland Finch, Christopher J Gaffney, Alan Gow, Eirini Kelaiditi, Andrzej Klimczuk, Esperanza Navarro-Pardo, Pheobe Sharratt, Andrew Sixsmith, Claudia K Suemoto, Lalu Suprawesta, Tamlyn Watermeyer, Sally Fowler Davis","doi":"10.3389/fnagi.2025.1541048","DOIUrl":"10.3389/fnagi.2025.1541048","url":null,"abstract":"<p><strong>Introduction: </strong>The conjunction of physical frailty and cognitive impairment without dementia is described as Cognitive Frailty (CF). Indications that CF is potentially reversible have led to proposals that risk factors, symptoms or mechanisms of CF would be appropriate targets for interventions for prevention, delay or reversal. However, no study has brought experts together across sectors to determine targets, content or mode of interventions, and most resources on interventions are from the perspective of academic or clinical researchers only. This international Delphi consensus study brings together experts from academic and clinical research, lay people with lived experience of CF, informal carers, and professional care practitioners/clinicians.</p><p><strong>Methods: </strong>Three rounds of Delphi study were held to discern which factors and statements were agreed upon by the whole sample and which generated different views in those with differing expertise. A scoping review and Round 1 (29 participants) were used to gather initial statements. In Round 2, 58 people responded to statements and open text items, comprising 7 lab-based researchers, 27 researchers working with people, 14 people with lived experience or informal family carers, and 10 professional carers/clinicians. Percent agreement and qualitative responses were analyzed to provide a final set of statements which were checked by 38 respondents in Round 3.</p><p><strong>Results: </strong>Analysis of Round 2 quantitative data provided 74 statements on which there was at least 70% agreement and qualitative data produced a further 24 statements. These were combined to provide 90 statements for Round 3. There was Consensus for 89 of the statements. A few differences between the groups were observed at both stages.</p><p><strong>Discussion and conclusion: </strong>The consensus for statements associated with CF interventions provides a useful first step in defining health promotion activities and interventions. Given the prevalence and potential disability caused by CF in older populations, the consensus statements represent expert opinion that is inter-sectoral and will inform public health policies to support implementation of evidence-based prevention and intervention plans. This study is an important step toward changing current approaches, by including all stakeholders from the outset. Outcomes can be used to feed into co-creation of interventions for cognitive frailty.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1541048"},"PeriodicalIF":4.1,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12174145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324936","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":"Association between sarcopenic obesity and dementia in the Chinese elderly using different definitions of obesity: evidence from the CHARLS.","authors":"Lang Peng, Qingwei Xiang, Ge Jia, Renyi Yin","doi":"10.3389/fnagi.2025.1540272","DOIUrl":"10.3389/fnagi.2025.1540272","url":null,"abstract":"<p><strong>Objectives: </strong>The prevalence of sarcopenic obesity, characterized by the coexistence of reduced muscle mass and function alongside increased adipose tissue, is increasing in the aging population. This study aims to investigate the association between sarcopenic obesity and dementia risk in community-dwelling older adults in China, utilizing a nationally representative dataset. Furthermore, we aim to assess the comparative effectiveness of waist circumference versus body mass index as indicators for assessing this risk association.</p><p><strong>Design: </strong>The study was designed as a cross-sectional study.</p><p><strong>Setting and participants: </strong>Based on the nationally representative data from the China Health and Retirement Longitudinal Study (CHARLS) 2015, a total of 5,320 community-dwelling participants aged 60 years and above were categorized into four groups according to their respective classifications of normal status, possible sarcopenia, obesity, and sarcopenic obesity.</p><p><strong>Methods: </strong>Multivariable logistic regression models were used to analyze the relationship between sarcopenic obesity and probable dementia while adjusting for potential confounders.</p><p><strong>Results: </strong>After adjusting for potential confounders, possible sarcopenia alone (<i>OR</i> 1.674, <i>95% CI</i> 1.238-2.264) and sarcopenic obesity (<i>OR</i> 1.812, <i>95% CI</i> 1.325-2.479) were significantly associated with an increased risk of probable dementia. In contrast, abdominal obesity alone, defined by waist circumference (WC), was not significantly associated with dementia risk. When stratified by age and gender, the association between sarcopenic obesity and probable dementia remained significant.</p><p><strong>Conclusion and implications: </strong>The findings from this cross-sectional study suggest that both possible sarcopenia and sarcopenic obesity are significantly associated with an increased risk of probable dementia among older adults residing in the community in China. Notably, the relationship between sarcopenic obesity and dementia appears to be more pronounced compared to either possible sarcopenia or obesity alone. Moreover, incorporating waist circumference alongside components of possible sarcopenia may serve as a more effective predictor of cognitive impairment when compared to relying solely on body mass index (BMI). These results underscore the critical importance of early identification and intervention for individuals with sarcopenic obesity to mitigate the risk of developing dementia.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1540272"},"PeriodicalIF":4.1,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12174056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324923","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":"Research progress of deubiquitinating enzymes in cerebral ischemia-reperfusion injury.","authors":"XiaoHong Qin, JiangRui Zhu, HaoRan Lu, MaoRui Yi, ZiLong Zhao, WenFei Zhang, Jing Cheng","doi":"10.3389/fnagi.2025.1588920","DOIUrl":"10.3389/fnagi.2025.1588920","url":null,"abstract":"<p><p>Cerebral ischemia-reperfusion injury (CIRI) is a critical pathological process driving neurological deterioration following ischemic stroke, involving multifaceted mechanisms such as inflammatory cascades, oxidative stress, and programmed cell death (PCD). Deubiquitinases (DUBs), as key regulators of the ubiquitin-proteasome system, dynamically modulate protein stability, signal transduction, and subcellular localization through editing the ubiquitin code, exhibiting dual roles in CIRI-both as drivers of pathogenesis and potential therapeutic targets. This review systematically elucidates the core regulatory mechanisms of DUBs in CIRI: (i) suppression of neuroinflammation via modulation of NLRP6/NF-κB pathways; (ii) mitigation of oxidative stress through the KEAP1-NRF2 axis and mitochondrial quality control; and (iii) neuroprotection by intercepting necroptosis, ferroptosis, and other PCD pathways. We further reveal that CIRI disrupts DUBs functionality through a tripartite mechanism-transcriptional dysregulation, catalytic inactivation, and subcellular mislocalization-transforming DUBs from guardians of homeostasis into mediators of injury. Consequently, DUBs-targeted strategies, including small-molecule inhibitors (e.g., IU1, Vialinin A), genetic editing approaches (e.g., BRCC3 silencing, A20 overexpression), and exosome-based delivery systems (e.g., the KLF3-AS1/miR-206/USP22 axis), demonstrate significant neuroprotective potential. However, challenges persist, such as substrate specificity, ubiquitin chain-type dependency, and barriers to clinical translation. Future research must integrate multi-omics technologies, develop brain-targeted delivery platforms, and explore synergistic effects of DUBs modulation with existing therapies to advance precision medicine in stroke treatment.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1588920"},"PeriodicalIF":4.1,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12171222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316357","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":"Neurobiological and therapeutic landmarks of depression associated with Alzheimer's disease dementia.","authors":"Ilinca Untu, Michael Davidson, Gabriela-Dumitrita Stanciu, Jonathan Rabinowitz, Romeo-Petru Dobrin, Diana-Sabina Vieru, Bogdan-Ionel Tamba","doi":"10.3389/fnagi.2025.1584607","DOIUrl":"10.3389/fnagi.2025.1584607","url":null,"abstract":"<p><p>Depression in Alzheimer's disease (AD) dementia has become an increasingly recognized public health concern due to its high prevalence and substantial impact on patient outcomes. Despite extensive research having been conducted over the past decades, the precise causal mechanisms and the nature of the relationship between depression and AD dementia remain incompletely understood. This narrative review examines the bidirectional interaction between depression and Alzheimer's disease, emphasizing shared neurobiological pathways, including neurotransmitter dysregulation, neuroinflammation, abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis, and deficits in neuroplasticity. These mechanisms likely contribute to the acceleration of neurodegeneration in AD and the onset or worsening of depressive symptoms. Current therapeutic approaches remain largely nonspecific, with a lack of targeted therapies that address the unique pathophysiological context of depression in AD. While progress has been made, key research gaps remain, particularly in understanding the complex biological interactions between these two conditions. Future research should focus on identifying specific biomarkers and developing personalized treatment strategies tailored to the neurobiological features of both depression and AD. By addressing these neurobiological mechanisms, we can develop more effective and targeted interventions, ultimately improving patient outcomes and advancing clinical care for this dual pathology.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1584607"},"PeriodicalIF":4.1,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12171374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316356","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":"Integrative single-cell and cell-free plasma RNA transcriptomics identifies biomarkers for early non-invasive AD screening.","authors":"Li Wu, Renxin Zhang, Yichao Wang, Shaoxing Dai, Naixue Yang","doi":"10.3389/fnagi.2025.1571783","DOIUrl":"10.3389/fnagi.2025.1571783","url":null,"abstract":"<p><strong>Introduction: </strong>Data-driven omics approaches have rapidly advanced our understanding of the molecular heterogeneity of Alzheimer's disease (AD). However, limited by the unavailability of brain tissue, there is an urgent need for a non-invasive tool to detect alterations in the AD brain. Cell-free RNA (cfRNA), which crosses the blood-brain barrier, could reflect AD brain pathology and serve as a diagnostic biomarker.</p><p><strong>Methods: </strong>Here, we integrated plasma-derived cfRNA-seq data from 337 samples (172 AD patients and 165 age-matched controls) with brain-derived single cell RNA-seq (scRNA-seq) data from 88 samples (46 AD patients and 42 controls) to explore the potential of cfRNA profiling for AD diagnosis. A systematic comparative analysis of cfRNA and brain scRNA-seq datasets was conducted to identify dysregulated genes linked to AD pathology. Machine learning models-including support vector machine, random forest, and logistic regression-were trained using cfRNA expression patterns of the identified gene set to predict AD diagnosis and classify disease progression stages. Model performance was rigorously evaluated using area under the receiver operating characteristic curve (AUC), with robustness assessed through cross-validation and independent validation cohorts.</p><p><strong>Results: </strong>Notably, we identified 34 dysregulated genes with consistent expression changes in both cfRNA and scRNA-seq. Machine learning models based on the cfRNA expression patterns of these 34 genes can accurately predict AD patients (the highest AUC = 89%) and effectively distinguish patients at early stage of AD. Furthermore, classifiers developed based on the expression of 34 genes in brain transcriptome data demonstrated robust predictive performance for assessing the risk of AD in the population (the highest AUC = 94%).</p><p><strong>Discussion: </strong>This multi-omics approach overcomes limitations of invasive brain biomarkers and noisy blood-based signatures. The 34-gene panel provides non-invasive molecular insights into AD pathogenesis and early screening. While cfRNA stability challenges clinical translation, our framework highlights the potential for precision diagnostics and personalized therapeutic monitoring in AD.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1571783"},"PeriodicalIF":4.1,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12162594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301532","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}