Ebenau, JL;
van der Lee, SJ;
Hulsman, M;
Tesi, N;
Jansen, IE;
Verberk, IMW;
van Leeuwenstijn, M;
... van der Flier, WM; + view all
(2021)
Risk of dementia in APOE ε4 carriers is mitigated by a polygenic risk score.
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
, 13
(1)
, Article e12229. 10.1002/dad2.12229.
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Abstract
Introduction: We investigated relationships among genetic determinants of Alzheimer's disease (AD), amyloid/tau/neurodegenaration (ATN) biomarkers, and risk of dementia. Methods: We studied cognitively normal individuals with subjective cognitive decline (SCD) from the Amsterdam Dementia Cohort and SCIENCe project. We examined associations between genetic variants and ATN biomarkers, and evaluated their predictive value for incident dementia. A polygenic risk score (PRS) was calculated based on 39 genetic variants. The APOE gene was not included in the PRS and was analyzed separately. Results: The PRS and APOE ε4 were associated with amyloid-positive ATN profiles, and APOE ε4 additionally with isolated increased tau (A-T+N-). A high PRS and APOE ε4 separately predicted AD dementia. Combined, a high PRS increased while a low PRS attenuated the risk associated with ε4 carriers. Discussion: Genetic variants beyond APOE are clinically relevant and contribute to the pathophysiology of AD. In the future, a PRS might be used in individualized risk profiling.
| Type: | Article |
|---|---|
| Title: | Risk of dementia in APOE ε4 carriers is mitigated by a polygenic risk score |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/dad2.12229 |
| Publisher version: | https://doi.org/10.1002/dad2.12229 |
| Language: | English |
| Additional information: | © 2021 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
| Keywords: | APOE, ATN classification, Alzheimer's disease, biomarkers, dementia, polygenic risk score, subjective cognitive decline |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Brain Repair and Rehabilitation |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10135535 |
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