Genetic overlap between Alzheimer's disease and blood lipid levels

Robert J. van der Linden, Lianne M. Reus, Ward de Witte, Betty M. Tijms, Marcel Olde Rikkert, Pieter Jelle Visser, Geert Poelmans

Research output: Contribution to JournalArticleAcademicpeer-review

2 Citations (Scopus)

Abstract

Late-onset Alzheimer's disease (AD) has a significant genetic component, but the molecular mechanisms through which genetic risk factors contribute to AD pathogenesis are unclear. We screened for genetic sharing between AD and the blood levels of 615 metabolites to elucidate how the polygenic architecture of AD affects metabolomic profiles. We retrieved summary statistics from genome-wide association studies of AD and the metabolite blood levels and assessed for shared genetic etiology, using a polygenic risk score-based approach. For the blood levels of 31 metabolites, all of which were lipids, we identified and replicated genetic sharing with AD. We also found a positive genetic concordance - implying that genetic risk factors for AD are associated with higher blood levels - for 16 of the 31 replicated metabolites. In the brain, lipids and their intermediate metabolites have essential structural and functional roles, such as forming and dynamically regulating synaptic membranes. Our results imply that genetic risk factors for AD affect lipid levels, which may be leveraged to develop novel treatment strategies for AD.
Original languageEnglish
Pages (from-to)189-195
Number of pages7
JournalNeurobiology of aging
Volume108
Early online date2021
DOIs
Publication statusPublished - Dec 2021

Keywords

  • Alzheimer's disease
  • Human genetics
  • Lipoproteins
  • Metabolomics: Brain
  • Polygenic Risk Scores (PRS)

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