Plasma MIA, CRP, and albumin predict cognitive decline in Parkinson’s Disease
Plasma MIA, CRP, and albumin predict cognitive decline in Parkinson’s Disease
ABSTRACT ObjectiveUsing a multi-cohort, Discovery-Replication-Validation design, we sought new plasma biomarkers that predict which PD individuals will experience cognitive decline. MethodsIn 108 Discovery Cohort PD individuals and 83 Replication Cohort PD individuals, we measured 940 plasma proteins on an aptamer-based platform. Using proteins associating with subsequent cognitive decline in both cohorts, we trained a logistic regression model to predict which PD patients showed fast (>=1 point drop/year on Montreal Cognitive Assessment (MoCA)) vs. slow (<1 point drop/year on MoCA) cognitive decline in the Discovery Cohort, testing it in the Replication Cohort. We developed alternate assays for the top three proteins and confirmed their ability to predict cognitive decline – defined by change in MoCA or development of incident Mild Cognitive Impairment (MCI) or dementia – in a Validation Cohort of 118 PD individuals. We investigated the top plasma biomarker for causal influence by Mendelian randomization. ResultsA model with only three proteins (Melanoma Inhibitory Activity Protein (MIA), C-Reactive Protein (CRP), albumin) separated Fast vs. Slow cognitive decline subgroups with an AUC of 0.80 in the Validation Cohort. Validation Cohort PD individuals in the top quartile of risk for cognitive decline based on this model were 4.4 times more likely to develop incident MCI or dementia than those in the lowest quartile. Genotypes at MIA SNP rs2233154 associated with MIA levels and cognitive decline, providing evidence for MIA’s causal influence. ConclusionsAn easily-obtained plasma-based predictor identifies PD individuals at risk for cognitive decline. MIA may participate causally in development of cognitive decline.
Shen Junchao、Zack Rebecca、Unger Travis L.、Tropea Thomas F.、Van Deerlin Vivianna M.、Xie Sharon X.、Amari Noor、Dewey Richard B. Jr.、Trojanowski John Q.、Posavi Marijan、Skrinak R. Tyler、Weintraub Daniel、Chen-Plotkin Alice S.
Departments of Neurology, University of PennsylvaniaDepartments of Neurology, University of PennsylvaniaDepartments of Neurology, University of PennsylvaniaDepartments of Neurology, University of PennsylvaniaDepartments of Pathology and Laboratory Medicine, University of PennsylvaniaDepartments of Biostatistics, Epidemiology and Informatics, University of PennsylvaniaDepartments of Neurology, University of PennsylvaniaDepartment of Neurology, University of Texas Southwestern Medical CenterDepartments of Neurology, University of PennsylvaniaDepartments of Neurology, University of PennsylvaniaDepartments of Neurology, University of PennsylvaniaDepartments of Psychiatry, Perelman School of Medicine, University of Pennsylvania||Parkinson?ˉs Disease Research, Education and Clinical Center (PADRECC), Philadelphia Veterans Affairs Medical CenterDepartments of Neurology, University of Pennsylvania
神经病学、精神病学医学研究方法基础医学
Parkinson’s diseasecognitive declinebiomarkersMIA
Shen Junchao,Zack Rebecca,Unger Travis L.,Tropea Thomas F.,Van Deerlin Vivianna M.,Xie Sharon X.,Amari Noor,Dewey Richard B. Jr.,Trojanowski John Q.,Posavi Marijan,Skrinak R. Tyler,Weintraub Daniel,Chen-Plotkin Alice S..Plasma MIA, CRP, and albumin predict cognitive decline in Parkinson’s Disease[EB/OL].(2025-03-28)[2025-04-27].https://www.medrxiv.org/content/10.1101/2022.03.16.22272456.点此复制
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