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Age-dependent effect of APOE and polygenic component on Alzheimer's disease

Bellou, Eftychia, Baker, Emily, Leonenko, Ganna, Bracher-Smith, Matthew, Daunt, Paula, Menzies, Georgina, Williams, Julie and Escott-Price, Valentina 2020. Age-dependent effect of APOE and polygenic component on Alzheimer's disease. Neurobiology of Aging 93 , pp. 69-77. 10.1016/j.neurobiolaging.2020.04.024

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Abstract

Alzheimer’s disease (AD) is a devastating neurodegenerative condition with significant genetic heritability. Several genes have been implicated in the onset of AD with the apolipoprotein E (APOE) gene being the strongest single genetic risk loci. Evidence suggests that the effect of APOE alters with age during disease progression. Here, we aim to investigate the impact of APOE and other variants outside the APOE region on AD risk in younger and older participants. Using data from both the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and the UK Biobank (UKBB) we computed the polygenic risk score (PRS) of each individual informed by the latest genetic study from the International Genomics of Alzheimer’s Project (IGAP). Our analysis showed that the effect of APOE on the disease risk is greater in younger participants and reduces as participant age increases. Our findings indicate the increased impact of PRS as participant age increases. Therefore, AD in older individuals can potentially be triggered by the cumulative effect of genes which are outside the APOE region.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Elsevier
ISSN: 0197-4580
Funders: MRC
Date of First Compliant Deposit: 2 June 2020
Date of Acceptance: 22 April 2020
Last Modified: 30 Jun 2020 14:50
URI: http://orca.cf.ac.uk/id/eprint/131449

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