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

Published version
Peer-reviewed

Repository DOI


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Authors

Zhu, Jingjing 
Liu, Shuai 
Walker, Keenan A 
Zhong, Hua 
Ghoneim, Dalia H 

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.

Description

Funder: Intramural Research Program of the National Institutes of Health (National Institute on Aging)


Funder: Florida State University; doi: http://dx.doi.org/10.13039/100006597


Funder: University of Hawaii Cancer Center

Keywords

Alzheimer’s disease, Genetic instrument, Protein biomarker, Risk, Humans, Alzheimer Disease, Proteomics, Risk Factors, Blood Proteins, Biomarkers, Genome-Wide Association Study

Journal Title

Alzheimers Res Ther

Conference Name

Journal ISSN

1758-9193
1758-9193

Volume Title

16

Publisher

Springer Science and Business Media LLC
Sponsorship
Medical Research Council (MR/L003120/1)
British Heart Foundation (None)
British Heart Foundation (RG/18/13/33946)
National Institute for Health and Care Research (IS-BRC-1215-20014)
MRC (MC_PC_23013)
Medical Research Council (HDR-23007)