Publication Date
1-1-2024
Journal
Frontiers in Neuroscience
DOI
10.3389/fnins.2024.1404377
PMID
39108314
PMCID
PMC11300309
PubMedCentral® Posted Date
7-23-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
polygenic score, Mendelian randomization, Alzheimer’s disease, plasma proteins, pQTL
Abstract
BACKGROUND: An increasing body of evidence suggests that neuroinflammation is one of the key drivers of late-onset Alzheimer's disease (LOAD) pathology. Due to the increased permeability of the blood-brain barrier (BBB) in older adults, peripheral plasma proteins can infiltrate the central nervous system (CNS) and drive neuroinflammation through interactions with neurons and glial cells. Because these inflammatory factors are heritable, a greater understanding of their genetic relationship with LOAD could identify new biomarkers that contribute to LOAD pathology or offer protection against it.
METHODS: We used a genome-wide association study (GWAS) of 90 different plasma proteins (
RESULTS: We identified four plasma protein level PGSs that were significantly associated (FDR-adjusted
CONCLUSION: Our results show that plasma HGF has a negative causal relationship with LOAD liability that is driven by pleiotropic SNPs possibly involved in other pathways. These findings suggest a low transferability between PGS and MR approaches, and future research should explore ways in which LOAD and the plasma proteome may interact.
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