Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

The levels of many blood proteins are associated with Alzheimer′s disease or its pathological hallmarks. Elucidating the molecular factors that control circulating levels of these proteins may help to identify proteins causally associated with the disease. Here, genome-wide and epigenome-wide studies (nindividuals≤1,064) were performed on plasma levels of 281 Alzheimer′s disease-associated proteins, identified by a systematic review of the literature. We quantified the contributions of genetic and epigenetic variation towards inter-individual variability in plasma protein levels. Sixty-one independent genetic and 32 epigenetic loci were associated with expression levels of 49 proteins; eight and 24 of these respective findings are previously unreported. Novel findings included an association between plasma TREM2 levels and a polymorphism and CpG site within the MS4A4A locus. Through Mendelian randomisation analyses, causal associations were observed between higher plasma TBCA and TREM2 levels and lower Alzheimer′s disease risk. Our data inform the regulation of biomarker levels and their relationships with Alzheimer′s disease.

Original publication

DOI

10.1101/2021.06.07.21258457

Type

Journal article

Publisher

Cold Spring Harbor Laboratory

Publication Date

11/06/2021