Department of Neurology, Oslo University Hospital, Oslo, Norway.
Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Mov Disord. 2024 Mar;39(3):596-601. doi: 10.1002/mds.29698. Epub 2023 Dec 20.
Genetics influence cognitive progression in Parkinson's disease, possibly through mechanisms related to Lewy and Alzheimer's disease pathology. Lysosomal polygenic burden has recently been linked to more severe Lewy pathology post mortem.
To assess the influence of lysosomal polygenic burden on cognitive progression in Parkinson's disease patients with low Alzheimer's disease risk.
Using Cox regression we assessed association between lysosomal polygenic scores and time to Montreal Cognitive Assessment score ≤ 21 in the Parkinson's Progression Markers Initiative cohort (n = 374), with replication in data from the Parkinson's Disease Biomarker Program (n = 777). Patients were stratified by Alzheimer's disease polygenic risk.
The lysosomal polygenic score was associated with faster progression of cognitive decline in patients with low Alzheimer's disease risk in both datasets (P = 0.0032 and P = 0.0054, respectively).
Our study supports complex interplay between genetics and neuropathology in Parkinson's disease-related cognitive impairment, emphasizing the role of lysosomal polygenic burden. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
遗传学通过与路易体和阿尔茨海默病病理学相关的机制影响帕金森病的认知进展。溶酶体多基因负担最近与死后更严重的路易体病理学有关。
评估溶酶体多基因负担对阿尔茨海默病风险低的帕金森病患者认知进展的影响。
使用 Cox 回归分析，我们评估了溶酶体多基因评分与帕金森病进展标志物倡议队列（n=374）中蒙特利尔认知评估评分≤21 的时间之间的关联，在帕金森病生物标志物计划的数据中进行了复制（n=777）。根据阿尔茨海默病多基因风险对患者进行分层。
在两个数据集（分别为 P=0.0032 和 P=0.0054）中，溶酶体多基因评分与低阿尔茨海默病风险患者认知下降的快速进展相关。
我们的研究支持帕金森病相关认知障碍中遗传学和神经病理学之间的复杂相互作用，强调了溶酶体多基因负担的作用。© 2023 作者。运动障碍由 Wiley 期刊代表国际帕金森病和运动障碍协会出版。
