NPJ Parkinson's Disease最新文献_第9页

Choroid plexus enlargement contributes to motor severity via regional glymphatic dysfunction in Parkinson’s disease 脉络膜丛扩大通过帕金森氏病的区域淋巴功能障碍增加运动严重程度

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-05-22 DOI: 10.1038/s41531-025-00971-8

Linyu Liu, Qiang Weng, Qing Cai, Xintong Yu, Weibin Huang, Shaohua Xie, Yan Shi, Huiting Li, Yuxuan Zhang, Jianping Hu, Mengcheng Li, Guannan Chen, Ning Wang, Xiang Lin, Ying Fu, Yu Lin

{"title":"Choroid plexus enlargement contributes to motor severity via regional glymphatic dysfunction in Parkinson’s disease","authors":"Linyu Liu, Qiang Weng, Qing Cai, Xintong Yu, Weibin Huang, Shaohua Xie, Yan Shi, Huiting Li, Yuxuan Zhang, Jianping Hu, Mengcheng Li, Guannan Chen, Ning Wang, Xiang Lin, Ying Fu, Yu Lin","doi":"10.1038/s41531-025-00971-8","DOIUrl":"https://doi.org/10.1038/s41531-025-00971-8","url":null,"abstract":"Choroid plexus (CP) enlargement and glymphatic dysfunction have been implicated in neurodegeneration, but their roles in Parkinson’s disease (PD) remain unclear. This retrospective cross-sectional study examined associations among CP volume, perivascular spaces (PVS), and motor symptom severity in 123 PD patients stratified by disease stage. MRI quantified CP volume and PVS, including dilated PVS (dPVS), across brain regions. CP-dPVS correlations were stronger in early-stage PD. Region-specific analyses revealed CP volume was associated with PVS in the midbrain and basal ganglia. CP-dPVS correlations emerged in midbrain, basal ganglia, and centrum semiovale. Correlation matrix and mediation analyses together confirmed that only basal ganglia dPVS was both significantly correlated with motor symptoms and served as a mediator, accounting for 30.52% of the association between CP volume and motor severity. These findings suggest that CP enlargement contributes to motor severity in PD, in part through regional glymphatic dysfunction localized to the basal ganglia.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"40 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Systematic review of wearables assessing medication effect on motor function and symptoms in Parkinson's disease. 可穿戴设备评估帕金森病运动功能和症状的药物效果的系统综述。

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-05-22 DOI: 10.1038/s41531-025-00943-y

Emma Packer,Héloïse Debelle,Harry G B Bailey,Rana Zia Ur Rehman,Alison J Yarnall,Lynn Rochester,Lisa Alcock,Silvia Del Din

{"title":"Systematic review of wearables assessing medication effect on motor function and symptoms in Parkinson's disease.","authors":"Emma Packer,Héloïse Debelle,Harry G B Bailey,Rana Zia Ur Rehman,Alison J Yarnall,Lynn Rochester,Lisa Alcock,Silvia Del Din","doi":"10.1038/s41531-025-00943-y","DOIUrl":"https://doi.org/10.1038/s41531-025-00943-y","url":null,"abstract":"To improve motor function and symptoms, people with Parkinson's (PwP) typically take dopaminergic medication. In PwP, wearable technology (WT) can provide objective insights into medication effect. This review aims to identify and explore literature which uses WT to quantify the effect of medication on motor function and symptoms in PwP (PROSPERO 2022 CRD42022310018). Nine databases were searched between January 2000-October 2024. Downs and Black quality appraisal assessed study quality. PRISMA guidelines were followed. Amongst the seventy-nine included studies, 50 different WTs were placed across 20 locations on the body, and medication effect was monitored on 13 different motor functions/symptoms. There was great heterogeneity amongst protocols, but many studies were performed in controlled environments, exploring short-term medication effects (ON vs OFF). Medication effect varied, improving certain variables, and having no effect on others. Future research should identify gold-standard protocols to explore medication effect in real-world settings, over prolonged periods.Registration and Protocol PROSPERO 2022 CRD42022310018.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"46 1","pages":"135"},"PeriodicalIF":8.7,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144122102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PINK1 deficiency rewires early immune responses in a mouse model of Parkinson’s disease triggered by intestinal infection 在肠道感染引发的帕金森病小鼠模型中，PINK1缺乏重新连接了早期免疫反应

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-05-22 DOI: 10.1038/s41531-025-00945-w

Sherilyn Junelle Recinto, Alexandra Kazanova, Lin Liu, Brendan Cordeiro, Shobina Premachandran, Hicham Bessaiah, Alexis Allot, Elia Afanasiev, Sriparna Mukherjee, Jessica Pei, Adam MacDonald, Moein Yaqubi, Heidi M. McBride, Diana Matheoud, Louis-Eric Trudeau, Samantha Gruenheid, Jo Anne Stratton

{"title":"PINK1 deficiency rewires early immune responses in a mouse model of Parkinson’s disease triggered by intestinal infection","authors":"Sherilyn Junelle Recinto, Alexandra Kazanova, Lin Liu, Brendan Cordeiro, Shobina Premachandran, Hicham Bessaiah, Alexis Allot, Elia Afanasiev, Sriparna Mukherjee, Jessica Pei, Adam MacDonald, Moein Yaqubi, Heidi M. McBride, Diana Matheoud, Louis-Eric Trudeau, Samantha Gruenheid, Jo Anne Stratton","doi":"10.1038/s41531-025-00945-w","DOIUrl":"https://doi.org/10.1038/s41531-025-00945-w","url":null,"abstract":"Parkinson’s disease is characterized by a period of non-motor symptoms, including gastrointestinal dysfunction, preceding motor deficits by several years to decades. This long prodrome is suggestive of peripheral immunity involvement in the initiation of disease. We previously developed a model system in PINK1 KO mice displaying PD-like motor symptoms at late stages following intestinal infections. Herein, we map the initiating immune events at the site of infection in this model. Using single-cell RNAseq, we demonstrate that peripheral myeloid cells are the earliest highly dysregulated immune cell type followed by an aberrant T cell response shortly after. We also demonstrate an increased propensity for antigen presentation and that activated myeloid cells acquire a proinflammatory profile capable of inducing cytotoxic T cell responses. Together, our study provides the first evidence that PINK1 is a key regulator of immune functions in the gut underlying early PD-related disease mechanisms.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"133 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The barriers to receiving health care for people with Parkinson’s from predominantly Asian backgrounds in the UK 在英国，主要来自亚洲背景的帕金森患者接受医疗保健的障碍

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-05-20 DOI: 10.1038/s41531-025-00946-9

Mouhammed Ramadhan, Joshua Stott, Anette Schrag

引用次数: 0

The impact of REM-sleep behavior disorder on people with Parkinson’s disease and their partners 快速眼动睡眠行为障碍对帕金森病患者及其伴侣的影响

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-05-17 DOI: 10.1038/s41531-025-00986-1

Eva M. Prins, Angelique Pijpers, Noortje Verbeek, Sirwan K. L. Darweesh, Angelika D. Geerlings, Marjan J. Meinders, Bastiaan R. Bloem, Karin D. van Dijk, Lisanne J. Dommershuijsen

{"title":"The impact of REM-sleep behavior disorder on people with Parkinson’s disease and their partners","authors":"Eva M. Prins, Angelique Pijpers, Noortje Verbeek, Sirwan K. L. Darweesh, Angelika D. Geerlings, Marjan J. Meinders, Bastiaan R. Bloem, Karin D. van Dijk, Lisanne J. Dommershuijsen","doi":"10.1038/s41531-025-00986-1","DOIUrl":"https://doi.org/10.1038/s41531-025-00986-1","url":null,"abstract":"REM-sleep behavior disorder (RBD) may affect health-related quality of life (HRQoL) of people with Parkinson’s disease (PwP) and partners. We aimed to determine how RBD affects HRQoL using a mixed-methods approach. Quantitatively, we analyzed data from the PRIME-NL Parkinson Evaluation study, including 829 PwP and 452 partners, using multivariable regression models to examine the association between screen-positive RBD and HRQoL. Qualitatively, we conducted interviews with 14 dyads of PwP with self-reported RBD and their partners. RBD was negatively associated with HRQoL in both groups, primarily due to short-term effects on daily life, co-existing symptoms like impaired cognition and autonomic issues, and sleep disturbances. Impact of RBD was already felt before or during the diagnostic process, with the main challenges being sleep-related complaints, anxiety and impact on relationships. PwP and partners employed both medical and non-medical coping strategies. These findings will help to optimize care for PwP with RBD and their partners.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"122 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144067156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Investigating glymphatic function and bed nucleus of the stria terminalis-based functional connectivity in Parkinson’s disease with and without depression 研究伴有和不伴有抑郁的帕金森病终末纹的淋巴功能和床核的功能连接

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-05-16 DOI: 10.1038/s41531-025-00985-2

Xiyong Dai, Yue Zhang, Chengwei Fu, Zhijie Gao, Xiaoyan Hou, Zhaoxian Yan, Chunye Zheng, Lei Gao, Bo Liu

{"title":"Investigating glymphatic function and bed nucleus of the stria terminalis-based functional connectivity in Parkinson’s disease with and without depression","authors":"Xiyong Dai, Yue Zhang, Chengwei Fu, Zhijie Gao, Xiaoyan Hou, Zhaoxian Yan, Chunye Zheng, Lei Gao, Bo Liu","doi":"10.1038/s41531-025-00985-2","DOIUrl":"https://doi.org/10.1038/s41531-025-00985-2","url":null,"abstract":"Glymphatic activity and the bed nucleus of the stria terminalis (BNST) have been implicated in the pathogenesis of Parkinson’s disease (PD) with depression (PDD). This study aimed to investigate glymphatic function and BNST-based functional connectivity (FC) and potential biomarkers in PDD. The diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index combined with BNST-based FC and support vector machine were applied to 24 PDD, 24 PD with non-depression (PDND), and 25 healthy controls. We found that (1) the DTI-ALPS indices (p < 0.001), the right BNST-based FC values (p < 0.001, FWE small volume correction) were significantly different among three groups; (2) the FC features in the right mPFC (mPFC_R), right MTG (MTG_R), and right ITG (ITG_R) can distinguish PDD from PDND; (3) the right BNST-based FC values, DTI-ALPS indices, and HAMD scores were correlated with each other (r = −0.620, p = 0.004; r = 0.651, p = 0.002; r = −0.53, p = 0.016). Impaired glymphatic function and altered BNST-based FC values are strongly associated with PD, and brain regions with differences in the right BNST-based FC values may serve as potential biomarkers for classifying clinical subtypes of PD. These findings provide new insights into the pathogenesis of depression in PD. This study protocol was registered on the Chinese Clinical Trial Registry (ChiCTR2000038411, September 22, 2020, https://www.chictr.org.cn/showproj.html?proj=56715).","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"124 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144066160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genetic risk and plasma biomarkers of dementia with Lewy bodies in a Chinese population. 中国人群路易体痴呆的遗传风险和血浆生物标志物。

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-05-15 DOI: 10.1038/s41531-025-00988-z

Xiaoli Hao,Xuewen Xiao,Ling Weng,Zhuojie Lin,Qian Xu,Juan Du,Qijie Yang,Yuan Zhu,Yiliang Liu,Tianyan Xu,Yafang Zhou,Xinxin Liao,Jifeng Guo,Shilin Luo,Junling Wang,Xinxiang Yan,Beisha Tang,Jinchen Li,Bin Jiao,Lu Shen

{"title":"Genetic risk and plasma biomarkers of dementia with Lewy bodies in a Chinese population.","authors":"Xiaoli Hao,Xuewen Xiao,Ling Weng,Zhuojie Lin,Qian Xu,Juan Du,Qijie Yang,Yuan Zhu,Yiliang Liu,Tianyan Xu,Yafang Zhou,Xinxin Liao,Jifeng Guo,Shilin Luo,Junling Wang,Xinxiang Yan,Beisha Tang,Jinchen Li,Bin Jiao,Lu Shen","doi":"10.1038/s41531-025-00988-z","DOIUrl":"https://doi.org/10.1038/s41531-025-00988-z","url":null,"abstract":"Genetic investigations and associations with plasma biomarkers of dementia with Lewy bodies (DLB) in East Asian populations are lacking. The aim of our study is to identify candidate pathogenic variants and assess the diagnostic performance of plasma biomarkers among DLB patients in the Chinese population. This cohort included 151 DLB patients and 2010 controls, all of whom underwent whole genome sequencing. Plasma glial fibrillary acidic protein (GFAP), α-synuclein(αSyn), neurofilament light (NfL), and phosphorylated tau 217 (p-tau217) were detected in a subgroup. As a result, the APOE ε4 allele significantly increased DLB risk (p = 1.84E-11), while rare missense variants of USP13 gene were first found to be suggestively associated with DLB risk (p = 1.31E-5). Higher levels of plasma GFAP, αSyn, NfL, and p-tau217 were detected in DLB patients compared to controls (p < 0.001), which combined with polygenic risk scores (PRS) achieving an AUC of 0.927 for DLB diagnosis. Besides, significant correlations were observed between PRS of DLB and age at onset, the cumulative incidence rate, as well as plasma GFAP levels. In conclusion, this is the first study to simultaneously investigate the genetics and plasma biomarkers of DLB, highlighting the discriminative ability for DLB using PRS and plasma biomarker assay.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"76 1","pages":"128"},"PeriodicalIF":8.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Differential memory enrichment of cytotoxic CD4 T cells in Parkinson’s disease patients reactive to α-synuclein α-突触核蛋白反应的帕金森病患者细胞毒性CD4 T细胞差异记忆富集

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-05-14 DOI: 10.1038/s41531-025-00981-6

Antoine Freuchet, Emil Johansson, April Frazier, Irene Litvan, Jennifer G. Goldman, Roy N. Alcalay, David Sulzer, Cecilia S. Lindestam Arlehamn, Alessandro Sette

{"title":"Differential memory enrichment of cytotoxic CD4 T cells in Parkinson’s disease patients reactive to α-synuclein","authors":"Antoine Freuchet, Emil Johansson, April Frazier, Irene Litvan, Jennifer G. Goldman, Roy N. Alcalay, David Sulzer, Cecilia S. Lindestam Arlehamn, Alessandro Sette","doi":"10.1038/s41531-025-00981-6","DOIUrl":"https://doi.org/10.1038/s41531-025-00981-6","url":null,"abstract":"Parkinson’s disease (PD) is a complex neurodegenerative disease with a largely unknown etiology. Although the loss of dopaminergic neurons in the substantia nigra pars compacta is the pathological hallmark of PD, neuroinflammation also plays a fundamental role in PD pathology. We have previously reported that PD patients have increased frequencies of T cells reactive to peptides from α-synuclein (α-syn). However, not all PD participants respond to α-syn. Furthermore, we have previously found that CD4 T cells from PD participants responding to α-syn (PD_R) are transcriptionally distinct from PD participants not responding to α-syn (PD_NR). To gain further insight into the pathology of PD_R participants, we investigated surface protein expression of 11 proteins whose genes had previously been found to be differentially expressed when comparing PD_R and healthy control participants not responding to α-syn (HC_NR). We found that Cadherin EGF LAG seven-pass G-type receptor 2 (CELSR2) was expressed on a significantly higher proportion of CD4 effector memory T cells (TEM) in PD_R compared to HC_NR. Single-cell RNA sequencing analysis of cells expressing or not expressing CELSR2 revealed that PD_R participants have elevated frequencies of activated TEM subsets and an almost complete loss of cytotoxic TEM cells. Flow cytometry analyses confirmed that Granulysin+ CD4 cytotoxic TEM cells are reduced in PD_R. Taken together, these results provide further insight into the perturbation of T cell subsets in PD_R, and highlights the need for further investigation into the role of Granulysin+ CD4 cytotoxic TEM in PD pathology.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"26 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Predicting dementia in people with Parkinson’s disease 预测帕金森病患者的痴呆

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-05-13 DOI: 10.1038/s41531-025-00983-4

Mohamed Aborageh, Tom Hähnel, Patricia Martins Conde, Jochen Klucken, Holger Fröhlich

{"title":"Predicting dementia in people with Parkinson’s disease","authors":"Mohamed Aborageh, Tom Hähnel, Patricia Martins Conde, Jochen Klucken, Holger Fröhlich","doi":"10.1038/s41531-025-00983-4","DOIUrl":"https://doi.org/10.1038/s41531-025-00983-4","url":null,"abstract":"Parkinson’s disease (PD) exhibits a variety of symptoms, with approximately 25% of patients experiencing mild cognitive impairment and 45% developing dementia within ten years of diagnosis. Predicting this progression and identifying its causes remains challenging. Our study utilizes machine learning and multimodal data from the UK Biobank to explore the predictability of Parkinson’s dementia (PDD) post-diagnosis, further validated by data from the Parkinson’s Progression Markers Initiative (PPMI) cohort. Using Shapley Additive Explanation (SHAP) and Bayesian Network structure learning, we analyzed interactions among genetic predisposition, comorbidities, lifestyle, and environmental factors. We concluded that genetic predisposition is the dominant factor, with significant influence from comorbidities. Additionally, we employed Mendelian randomization (MR) to establish potential causal links between hypertension, type 2 diabetes, and PDD, suggesting that managing blood pressure and glucose levels in Parkinson’s patients may serve as a preventive strategy. This study identifies risk factors for PDD and proposes avenues for prevention.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"43 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cortical microstructural abnormalities in dementia with Lewy bodies and their associations with Alzheimer’s disease copathologies 路易体痴呆患者皮层微结构异常及其与阿尔茨海默病病理的关系

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-05-12 DOI: 10.1038/s41531-025-00944-x

Elijah Mak, Robert I. Reid, Scott A. Przybelski, Angela M. Fought, Timothy G. Lesnick, Christopher G. Schwarz, Matthew L. Senjem, Sheelakumari Raghavan, Prashanthi Vemuri, Clifford R. Jack, Hoon Ki Min, Manoj K. Jain, Toji Miyagawa, Leah K. Forsberg, Julie A. Fields, Rodolfo Savica, Jonathan Graff-Radford, David T. Jones, Hugo Botha, Erik K. St. Louis, David S. Knopman, Vijay K. Ramanan, Dennis W. Dickson, Neill R. Graff-Radford, Gregory S. Day, Tanis J. Ferman, Ronald C. Petersen, Val J. Lowe, Bradley F. Boeve, John T. O’Brien, Kejal Kantarci

{"title":"Cortical microstructural abnormalities in dementia with Lewy bodies and their associations with Alzheimer’s disease copathologies","authors":"Elijah Mak, Robert I. Reid, Scott A. Przybelski, Angela M. Fought, Timothy G. Lesnick, Christopher G. Schwarz, Matthew L. Senjem, Sheelakumari Raghavan, Prashanthi Vemuri, Clifford R. Jack, Hoon Ki Min, Manoj K. Jain, Toji Miyagawa, Leah K. Forsberg, Julie A. Fields, Rodolfo Savica, Jonathan Graff-Radford, David T. Jones, Hugo Botha, Erik K. St. Louis, David S. Knopman, Vijay K. Ramanan, Dennis W. Dickson, Neill R. Graff-Radford, Gregory S. Day, Tanis J. Ferman, Ronald C. Petersen, Val J. Lowe, Bradley F. Boeve, John T. O’Brien, Kejal Kantarci","doi":"10.1038/s41531-025-00944-x","DOIUrl":"https://doi.org/10.1038/s41531-025-00944-x","url":null,"abstract":"Dementia with Lewy bodies (DLB) frequently coexists with Alzheimer’s disease pathology, yet the pattern of cortical microstructural injury and its relationship with amyloid, tau, and cerebrovascular pathologies remains unclear. We applied neurite orientation dispersion and density imaging (NODDI) to assess cortical microstructural integrity in 57 individuals within the DLB spectrum and 57 age- and sex-matched cognitively unimpaired controls by quantifying mean diffusivity (MD), tissue-weighted neurite density index (tNDI), orientation dispersion index (ODI), and free water fraction (FWF). Amyloid and tau levels were measured using PiB and Flortaucipir PET imaging. Compared to controls, DLB exhibited increased MD and FWF, reduced tNDI across multiple regions, and focal ODI reductions in the occipital cortex. Structural equation modeling revealed that APOE genotype influenced amyloid levels, which elevated tau, leading to microstructural injury. These findings highlight the role of AD pathology in DLB neurodegeneration, advocating for multi-target therapeutic approaches addressing both AD and DLB-specific pathologies.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"54 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143933463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0