Author:
Zhu Jingjing,Liu Shuai,Walker Keenan A.,Zhong Hua,Ghoneim Dalia H.,Zhang Zichen,Surendran Praveen,Fahle Sarah,Butterworth Adam,Alam Md Ashad,Deng Hong-Wen,Wu Chong,Wu Lang
Abstract
Abstract
Background
Specific peripheral proteins have been implicated to play an important role in the development of Alzheimer’s disease (AD). However, the roles of additional novel protein biomarkers in AD etiology remains elusive. The availability of large-scale AD GWAS and plasma proteomic data provide the resources needed for the identification of causally relevant circulating proteins that may serve as risk factors for AD and potential therapeutic targets.
Methods
We established and validated genetic prediction models for protein levels in plasma as instruments to investigate the associations between genetically predicted protein levels and AD risk. We studied 71,880 (proxy) cases and 383,378 (proxy) controls of European descent.
Results
We identified 69 proteins with genetically predicted concentrations showing associations with AD risk. The drugs almitrine and ciclopirox targeting ATP1A1 were suggested to have a potential for being repositioned for AD treatment.
Conclusions
Our study provides additional insights into the underlying mechanisms of AD and potential therapeutic strategies.
Funder
Intramural Research Program of the National Institutes of Health
Florida State University
University of Hawaii Cancer Center
Publisher
Springer Science and Business Media LLC
Subject
Cognitive Neuroscience,Neurology (clinical),Neurology
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