Frontiers in Aging Neuroscience最新文献

{"title":"Investigating causality and shared genetic architecture between body mass index and cognitive function: a genome-wide cross-trait analysis and bi-directional Mendelian randomization study.","authors":"Mingyi Chen, Xiaoxin Xu, Fang Wang, Xiaohong Xu","doi":"10.3389/fnagi.2024.1466799","DOIUrl":"10.3389/fnagi.2024.1466799","url":null,"abstract":"<p><strong>Background and objectives: </strong>Observational studies have established a connection between body mass index (BMI) and an increased risk of cognitive decline. However, a comprehensive investigation into the causal relationships between BMI and cognitive function across diverse age groups, as well as the genetic underpinnings of this relationship, has been notably lacking. This study aims to investigate causality and the shared genetic underpinnings of between BMI and cognitive function by conducting a thorough genome-wide analysis, thereby provide valuable insights for developing personalized intervention strategies to promote cognitive health.</p><p><strong>Methods: </strong>Genetic associations between BMI and cognitive function were thoroughly investigated through covariate genetic analysis and chained imbalance score regression, utilizing data from genome-wide association studies (GWAS). Bi-directional Mendelian Randomization (MR) was employed to uncover associations and potential functional genes were further scrutinized through Cross-trait meta-analysis and Summary-data-based MR (SMR). Subsequently, a detailed examination of the expression profiles of the identified risk SNPs in tissues and cells was conducted.</p><p><strong>Results: </strong>The study found a significant negative correlation between BMI and cognitive function (β = -0.16, <i>P</i> = 1.76E-05), suggesting a causal linkage where higher BMI values were predictive of cognitive impairment. We identified 5 genetic loci (rs6809216, rs7187776, rs11713193, rs13096480, and rs13107325) between BMI and cognitive function by cross-trait meta-analysis and 5 gene-tissue pairs were identified by SMR analysis. Moreover, two novel risk genes <i>TUFM</i> and <i>MST1R</i> were shared by both cross-trait analysis and SMR analysis, which had not been observed in previous studies. Furthermore, significant enrichment of single nucleotide polymorphisms (SNPs) at tissue- and cell-specific levels was identified for both BMI and cognitive function, predominantly within the brain.</p><p><strong>Conclusion: </strong>This study uncovers a causal relationship between BMI and cognitive function, with the discovery of <i>TUFM</i> and <i>MST1R</i> as shared genetic factors associated with both conditions. This novel finding offers new insights into the development of preventative strategies for cognitive decline in obese individuals, and further enhances our understanding of the underlying pathophysiology of these conditions. Furthermore, these findings could serve as a guide for the development of innovative therapeutic approaches to address cognitive decline in obese individuals.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"16 ","pages":"1466799"},"PeriodicalIF":4.1,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11522962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544735","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":"Machine learning-based personalized composite score dissects risk and protective factors for cognitive and motor function in older participants.","authors":"Ann-Kathrin Schalkamp, Stefanie Lerche, Isabel Wurster, Benjamin Roeben, Milan Zimmermann, Franca Fries, Anna-Katharina von Thaler, Gerhard Eschweiler, Walter Maetzler, Daniela Berg, Fabian H Sinz, Kathrin Brockmann","doi":"10.3389/fnagi.2024.1447944","DOIUrl":"https://doi.org/10.3389/fnagi.2024.1447944","url":null,"abstract":"<p><strong>Introduction: </strong>With age, sensory, cognitive, and motor abilities decline, and the risk for neurodegenerative disorders increases. These impairments influence the quality of life and increase the need for care, thus putting a high burden on society, the economy, and the healthcare system. Therefore, it is important to identify factors that influence healthy aging, particularly ones that are potentially modifiable through lifestyle choices. However, large-scale studies investigating the influence of multi-modal factors on a global description of healthy aging measured by multiple clinical assessments are sparse.</p><p><strong>Methods: </strong>We propose a machine learning model that simultaneously predicts multiple cognitive and motor outcome measurements on a personalized level recorded from one learned composite score. This personalized composite score is derived from a large set of multi-modal components from the TREND cohort, including genetic, biofluid, clinical, demographic, and lifestyle factors.</p><p><strong>Results: </strong>We found that a model based on a single composite score was able to predict cognitive and motor abilities almost as well as a classical flexible regression model specifically trained for each single clinical score. In contrast to the flexible regression model, our composite score model is able to identify factors that globally influence cognitive and motoric abilities as measured by multiple clinical scores. The model identified several risk and protective factors for healthy aging and recovered physical exercise as a major, modifiable, protective factor.</p><p><strong>Discussion: </strong>We conclude that our low parametric modeling approach successfully recovered known risk and protective factors of healthy aging on a personalized level while providing an interpretable composite score. We suggest validating this modeling approach in other cohorts.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"16 ","pages":"1447944"},"PeriodicalIF":4.1,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11518739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544736","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":"Editorial: Model organisms in neuroinflammation and neuropathy: <i>Drosophila melanogaster</i>.","authors":"Zihan Huang, Xueji Dai, Baichun Jiang, Yan Kong","doi":"10.3389/fnagi.2024.1502502","DOIUrl":"10.3389/fnagi.2024.1502502","url":null,"abstract":"","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"16 ","pages":"1502502"},"PeriodicalIF":4.1,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521546","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":"Diffusion and functional MRI reveal microstructural and network connectivity impairment in adult-onset neuronal intranuclear inclusion disease.","authors":"Rui Zhu, Junyu Qu, Yongsheng Wu, Guihua Xu, Dawei Wang","doi":"10.3389/fnagi.2024.1478065","DOIUrl":"10.3389/fnagi.2024.1478065","url":null,"abstract":"<p><strong>Objectives: </strong>Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder lacking reliable neuroimaging biomarkers. This study aimed to evaluate microstructural and functional connectivity alterations using diffusion kurtosis imaging (DKI) and resting-state fMRI (rs-fMRI), and to investigate their diagnostic potential as biomarkers.</p><p><strong>Methods: </strong>Twenty-three patients with NIID and 40 matched healthy controls (HCs) were recruited. Firstly, gray matter (GM) and white matter (WM) changes were assessed by voxel-based analysis (VBA) and tract-based spatial statistics (TBSS). Then we explored modifications in brain functional networks connectivity by independent component analysis. And the relationship between the altered DKI parameters and neuropsychological evaluation was analyzed. Finally, a receiver operating characteristic (ROC) curve was used to evaluate the diagnostic performance of different gray matter and white matter parameters.</p><p><strong>Results: </strong>Compared with the HCs, NIID patients showed reduced mean kurtosis (MK), radial kurtosis (RK), axial kurtosis (AK), and kurtosis fractional anisotropy (KFA) values in deep gray matter regions. Significantly decreased MK, RK, AK, KFA and fractional anisotropy (FA), and increased mean diffusivity (MD) values were observed in extensive white matter fiber tracts. Notable alterations in functional connectivity were also detected. Among all DKI parameters, the diagnostic efficiency of AK in GM and FA in WM regions was the highest.</p><p><strong>Conclusion: </strong>Adult-onset NIID patients exhibited altered microstructure and functional network connectivity. Our findings suggest that DKI parameters may serve as potential imaging biomarkers for diagnosing adult-onset NIID.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"16 ","pages":"1478065"},"PeriodicalIF":4.1,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11502314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498103","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":"Genetically stratified Parkinson's disease with freezing of gait is related to specific pattern of cognitive impairment and non-motor dominant endophenotype.","authors":"Lukas Pavelka, Rajesh Rawal, Stefano Sapienza, Jochen Klucken, Claire Pauly, Venkata Satagopam, Rejko Krüger","doi":"10.3389/fnagi.2024.1479572","DOIUrl":"10.3389/fnagi.2024.1479572","url":null,"abstract":"<p><strong>Background: </strong>Freezing of gait (FOG) is an important milestone in the individual disease trajectory of people with Parkinson's disease (PD). Based on the <i>cognitive model</i> of FOG etiology, the mechanism behind FOG implies higher executive dysfunction in PD^FOG+. To test this model, we investigated the FOG-related phenotype and cognitive subdomains in idiopathic PD (iPD) patients without genetic variants linked to PD from the Luxembourg Parkinson's study.</p><p><strong>Methods: </strong>A cross-sectional analysis comparing iPD^FOG+ (<i>n</i> = 118) and iPD^FOG- (<i>n</i> = 378) individuals was performed, followed by the application of logistic regression models. Consequently, regression models were fitted for a subset of iPD^FOG+ (<i>n</i> = 35) vs. iPD^FOG- (<i>n</i> = 126), utilizing a detailed neuropsychological battery to assess the association between FOG and cognitive subdomains. Both regression models were adjusted for sociodemographic confounders and disease severity.</p><p><strong>Results: </strong>iPD^FOG+ individuals presented with more motor complications (MDS-UPDRS IV) compared to iPD^FOG- individuals. Moreover, iPD^FOG+ individuals exhibited a higher non-motor burden, including a higher frequency of hallucinations, higher MDS-UPDRS I scores, and more pronounced autonomic dysfunction as measured by the SCOPA-AUT. In addition, iPD^FOG+ individuals showed lower sleep quality along with lower quality of life (measured by PDSS and PDQ-39, respectively). The cognitive subdomain analysis in iPD^FOG+ vs. iPD^FOG- indicated lower scores in Benton's Judgment of Line Orientation test and CERAD word recognition, reflecting higher impairment in visuospatial, executive function, and memory encoding.</p><p><strong>Conclusion: </strong>We determined a significant association between FOG and a clinical endophenotype of PD with higher non-motor burden. While our results supported the cognitive model of FOG, our findings point to a more widespread cortical impairment across cognitive subdomains beyond the executive domain in PD^FOG+ with additional higher impairment in visuospatial function and memory encoding.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"16 ","pages":"1479572"},"PeriodicalIF":4.1,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11502444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498105","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 of frailty and serum neurofilament light chain levels: the mediating role of estimated glomerular filtration rate.","authors":"Wei Yang, Shan Huang, Huanshun Xiao, Pei Tao, Shuangming Cai","doi":"10.3389/fnagi.2024.1475505","DOIUrl":"10.3389/fnagi.2024.1475505","url":null,"abstract":"<p><strong>Background: </strong>Both frailty and elevated serum neurofilament light chain (sNfL) levels are linked to cognitive impairment. However, evidence of their relationship is lacking, and whether it was mediated by renal function was unknown. This study aimed to investigate the association between frailty and sNfL levels in a representative U.S. population, and to explore the potential mediating role of estimated glomerular filtration rate (eGFR) in this relationship.</p><p><strong>Methods: </strong>Data from 1,782 participants aged 20-75 years in the 2013-2014 National Health and Nutrition Examination Survey (NHANES) were analyzed. Frailty was assessed using a 49-item frailty index, and participants were categorized as non-frail, pre-frail, or frail. sNfL levels were measured using acoustic emission technology. Multivariable linear regression models and restricted cubic spline analyses were employed to examine the associations between frailty, eGFR, and sNfL levels. Mediation analysis was conducted to evaluate the role of eGFR in the frailty-sNfL relationship.</p><p><strong>Results: </strong>The prevalence of pre-frailty and frailty was 45.39 and 11.60%, respectively. A significant positive association was observed between frailty score and sNfL levels (adjusted <i>β</i>: 39.97, SE: 11.07, <i>p</i> = 0.003), with a linear relationship confirmed by restricted cubic spline analysis. Frail individuals had significantly higher sNfL levels compared to non-frail participants (adjusted <i>β</i>: 11.86, SE: 5.42, <i>p</i> = 0.04). eGFR was negatively associated with sNfL levels (adjusted β: -0.23, SE: 0.05, <i>p</i> < 0.001). Mediation analysis revealed that eGFR accounted for 12.52% of the total effect of frailty on sNfL levels (<i>p</i> < 0.0001).</p><p><strong>Conclusion: </strong>This study demonstrates a significant association between frailty and elevated sNfL levels in a representative U.S. population, with eGFR partially mediating this relationship. These findings suggest that sNfL may serve as a potential biomarker for frailty-related neuronal damage and highlight the importance of kidney function in this association. Further research is warranted to explore the clinical implications of these findings in frailty assessment and management strategies.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"16 ","pages":"1475505"},"PeriodicalIF":4.1,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11502322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498102","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":"Neural effects of multisensory dance training in Parkinson's disease: evidence from a longitudinal neuroimaging single case study.","authors":"Jenny R Simon, Judith Bek, Katayoun Ghanai, Karolina A Bearss, Rebecca E Barnstaple, Rachel J Bar, Joseph F X DeSouza","doi":"10.3389/fnagi.2024.1398871","DOIUrl":"https://doi.org/10.3389/fnagi.2024.1398871","url":null,"abstract":"<p><p>Dance is associated with beneficial outcomes in motor and non-motor domains in Parkinson's disease (PD) and regular participation may help delay symptom progression in mild PD. However, little is known about the neurobiological mechanisms of dance interventions for PD. The present case study explored potential neuroplastic changes in a 69-year-old male with mild PD participating in regular dance classes over 29 weeks. Functional MRI was performed at four timepoints (pre-training, 11 weeks, 18 weeks, 29 weeks), where the individual imagined a dance choreography while listening to the corresponding music. Neural activity was compared between dance-imagery and fixation blocks at each timepoint. Analysis of functionally defined regions revealed significant blood-oxygen-level-dependent (BOLD) signal activation in the supplementary motor area, right and left superior temporal gyri and left and right insula, with modulation of these regions observed over the training period except for the left insula. The results suggest the potential for dance to induce neuroplastic changes in people with PD in regions associated with motor planning and learning, auditory processing, rhythm, emotion, and multisensory integration. The findings are consistent with dance being a multimodal therapeutic activity that could provide long-term benefits for people with PD.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"16 ","pages":"1398871"},"PeriodicalIF":4.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498120","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":"Machine learning models for diagnosing Alzheimer's disease using brain cortical complexity.","authors":"Shaofan Jiang, Siyu Yang, Kaiji Deng, Rifeng Jiang, Yunjing Xue","doi":"10.3389/fnagi.2024.1434589","DOIUrl":"https://doi.org/10.3389/fnagi.2024.1434589","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to develop and validate machine learning models (MLMs) to diagnose Alzheimer's disease (AD) using cortical complexity indicated by fractal dimension (FD).</p><p><strong>Methods: </strong>A total of 296 participants with normal cognitive (NC) function and 182 with AD from the AD Neuroimaging Initiative database were randomly divided into training and internal validation cohorts. Then, FDs, demographic characteristics, baseline global cognitive function scales [Montreal Cognitive Assessment (MoCA), Functional Activities Questionnaire (FAQ), Global Deterioration Scale (GDS), Neuropsychiatric Inventory (NPI)], phospho-tau (p-tau 181), amyloidβ-42/40, apolipoprotein E (APOE) and polygenic hazard score (PHS) were collected to establish multiple MLMs. Receiver operating characteristic curves were used to evaluate model performance. Participants from our institution (<i>n</i> = 66; 33 with NC and 33 with AD) served as external validation cohorts to validate the MLMs. Decision curve analysis was used to estimate the models' clinical values.</p><p><strong>Results: </strong>The FDs from 30 out of 69 regions showed significant alteration. All MLMs were conducted based on the 30 significantly different FDs. The FD model had good accuracy in predicting AD in three cohorts [area under the receiver operating characteristic (ROC) curve (AUC) = 0.842, 0.808, and 0.803]. There were no statistically significant differences in AUC values between the FD model and the other combined models in the training and internal validation cohorts except MoCA + FD and FAQ + FD models. Among MLMs, the MoCA + FD model showed the best predictive efficiency in three cohorts (AUC = 0.951, 0.931, and 0.955) and had the highest clinical net benefit.</p><p><strong>Conclusion: </strong>The FD model showed favorable diagnostic performance for AD. Among MLMs, the MoCA + FD model can predict AD with the highest efficiency and could be used as a non-invasive diagnostic method.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"16 ","pages":"1434589"},"PeriodicalIF":4.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11500324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498119","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":"Sources of perceived social support and cognitive function among older adults: a longitudinal study in rural China.","authors":"Shiqi Gui, Jing Wang, Qiushuo Li, Hao Chen, Zhiyue Jiang, Jin Hu, Xing Yang, Jingyuan Yang","doi":"10.3389/fnagi.2024.1443689","DOIUrl":"https://doi.org/10.3389/fnagi.2024.1443689","url":null,"abstract":"<p><strong>Background: </strong>Studies have shown the positive impact of perceived social support on cognitive function among older adults in rural areas. However, existing studies often overlook the impact of different support sources. This study aimed to explore the relationship between the diverse sources of perceived social support and cognitive function.</p><p><strong>Methods: </strong>Participants were drawn from the Guizhou Rural Older Adults' Health Study (HSRO) in China. We included 791 participants who participated in a baseline survey in 2019 and a 3-year follow-up survey. Perceived social support was investigated from the six main sources (friend, relative, children, spouse, sibling, and neighbor). Hierarchical linear regression models were used to observe the effects of diverse sources of perceived social support and their combinations on cognitive function.</p><p><strong>Results: </strong>Cognitive function was positively associated with perceived support from children, friends, and neighbors. A positive association was found between cognitive function and increases in each additional source [<i>β</i> = 0.75 (95%CI: 0.51, 0.98), <i>p</i> < 0.001]. Older adults who perceived support from both children and friends showed better cognitive function [<i>β</i> = 2.53 (95%CI: 1.35, 3.72), <i>p</i> < 0.001]. The perception of support from spouse, siblings, and relatives did not show a statistically significant association with cognitive function among older adults in rural areas.</p><p><strong>Conclusion: </strong>This study found that the association between different sources of perceived social support and cognitive function was varied. This study provides scientific evidence that personalized support strategies may benefit in promoting cognitive health in rural older adults.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"16 ","pages":"1443689"},"PeriodicalIF":4.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496072/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498122","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":"Emerging role of microglia in inter-cellular transmission of α-synuclein in Parkinson's disease.","authors":"Xiangbo Zhang, Haiyang Yu, Juan Feng","doi":"10.3389/fnagi.2024.1411104","DOIUrl":"https://doi.org/10.3389/fnagi.2024.1411104","url":null,"abstract":"<p><p>Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide, significantly prejudicing the health and quality of life of elderly patients. The main pathological characteristics of PD are the loss of dopaminergic neurons in the substantia nigra (SN) as well as abnormal aggregation of α-synuclein (α-syn) monomers and oligomers, which results in formation of Lewy bodies (LBs). Intercellular transmission of α-syn is crucial for PD progression. Microglia play diverse roles in physiological and pathological conditions, exhibiting neuroprotective or neurotoxic effects; moreover, they may directly facilitate α-syn propagation. Various forms of extracellular α-syn can be taken up by microglia through multiple mechanisms, degraded or processed into more pathogenic forms, and eventually released into extracellular fluid or adjacent cells. This review discusses current literature regarding the molecular mechanisms underlying the uptake, degradation, and release of α-syn by microglia.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"16 ","pages":"1411104"},"PeriodicalIF":4.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498104","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}