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Alzheimer's disease susceptibility gene apolipoprotein e (APOE) and blood biomarkers in UK Biobank (N=395,769).

By Amy C. Ferguson, Rachana Tank, Laura M. Lyall, Joey Ward, Carlos A Celis-Morales, Rona J. Strawbridge, Frederick Ho, Christopher D. Whelan, Jason Gill, Paul Welsh, Jana J. Anderson, Patrick B Mark, Daniel F. Mackay, Daniel J Smith, Jill Pell, Jonathan Cavanagh, Naveed Sattar, Donald M. Lyall

Posted 13 Feb 2020
medRxiv DOI: 10.1101/2020.02.12.20021998

Background and objectiveAlzheimers disease (AD) is a neurodegenerative condition where the underlying aetiology is still unclear. Investigating the potential influence of apolipoprotein e (APOE), a major genetic risk factor, on common blood biomarkers could provide a greater understanding of the mechanisms of AD and dementia risk. Our objective was to conduct the largest (to date) single-protocol investigation of blood biomarkers in the context of APOE genotype, in UK Biobank. MethodsAfter quality control and exclusions, data on 395,769 participants of White European ancestry were available for analysis. Linear regressions were used to test potential associations between APOE genotypes and biomarkers. ResultsSeveral biomarkers significantly associated with APOE e4 risk and e2 protective genotypes (vs. neutral e3/e3). Most associations supported previous data: for example, e4 genotype was associated with elevated low-density lipoprotein cholesterol (LDL) (standardized beta [b] = 0.150 standard deviations [SDs] per allele, p<0.001) and e2 with lower LDL (b = -0.456 SDs, p<0.001). There were however instances of associations found in unexpected directions: e.g. e4 and increased insulin-like growth factor (IGF-1) (standardized beta = 0.017, p<0.001) where lower levels have been previously suggested as an AD risk factor. ConclusionsThese findings highlight biomarker differences in non-demented people at genetic risk for dementia. The evidence here in supports previous hypotheses of involvement from cardiometabolic and neuroinflammatory pathways.

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