Associations between genetically predicted plasma protein levels and Alzheimer's disease risk: a study using genetic prediction models

Zhu JJ, Liu S, Walker KA, Zhong H, Ghoneim DH, Zhang ZC, Surendran P, Fahle S, Butterworth A, Alam MA, Deng HW, Wu C, Wu L

BackgroundSpecific 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.MethodsWe 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.ResultsWe 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.ConclusionsOur study provides additional insights into the underlying mechanisms of AD and potential therapeutic strategies.

ScholarlyWork@Ochsner