Tin, Adrienne, Jennings, Lori, Gudnason, Vilmundur and Mosley, Thomas H (2022) Proteomic analysis identifies circulating proteins associated with plasma amyloid βeta and incident dementia. Biological Psychiatry Global Open Science. ISSN 26671743

Abstract

Background
Plasma amyloid beta (Aβ42, Aβ40, and Aβ42/Aβ40), biomarkers of the Alzheimer’s form of dementia, are under consideration for clinical use. The associations of these peptides with circulating proteins may identify novel plasma biomarkers of dementia and inform peripheral factors influencing the levels of these peptides.

Methods
We analyzed the association of these three plasma Aβ measures with 4,638 circulating proteins among a subset of the participants of the Atherosclerosis Risk in Communities (ARIC) study (midlife: n=1,955; late-life: n=2,082), related the Aβ-associated proteins with incident dementia in the overall ARIC cohort (midlife: n=11,069, late-life: n=4,110) with external replication in the Age, Gene/Environment Susceptibility (AGES) - Reykjavik Study (n=4,973), estimated the proportion of Aβ variance explained, and conducted enrichment analyses to characterize the proteins associated with the plasma Aβ peptides.

Results
At midlife, of the 296 Aβ-associated proteins, 8 were associated with incident dementia from midlife and late-life in ARIC, and NPPB, IBSP, and THBS2 were replicated in AGES. At late-life, of the 34 Aβ-associated proteins, none were associated with incident dementia at midlife, and kidney function explained 10%, 12%, 0.2% of the variance of Aβ42, Aβ40, and Aβ42/Aβ40, respectively. Aβ42-associated proteins at midlife were found to be enriched in the liver and those at late-life were found to be enriched in the spleen.

Conclusions
This study identifies circulating proteins associated with plasma Aβ levels and incident dementia and informs peripheral factors associated with plasma Aβ levels.

Item Type:	Article
Date Deposited:	08 Jun 2022 00:45
Last Modified:	08 Jun 2022 00:45
URI:	https://oak.novartis.com/id/eprint/45305