Deming, Y;
Vasiljevic, E;
Morrow, A;
Miao, J;
Van Hulle, C;
Jonaitis, E;
Ma, Y;
... Engelman, CD; + view all
(2023)
Neuropathology-based APOE genetic risk score better quantifies Alzheimer's risk.
Alzheimer's and Dementia
10.1002/alz.12990.
(In press).
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Abstract
Introduction: Apolipoprotein E (APOE) ε4-carrier status or ε4 allele count are included in analyses to account for the APOE genetic effect on Alzheimer's disease (AD); however, this does not account for protective effects of APOE ε2 or heterogeneous effect of ε2, ε3, and ε4 haplotypes. Methods: We leveraged results from an autopsy-confirmed AD study to generate a weighted risk score for APOE (APOE-npscore). We regressed cerebrospinal fluid (CSF) amyloid and tau biomarkers on APOE variables from the Wisconsin Registry for Alzheimer's Prevention (WRAP), Wisconsin Alzheimer's Disease Research Center (WADRC), and Alzheimer's Disease Neuroimaging Initiative (ADNI). Results: The APOE-npscore explained more variance and provided a better model fit for all three CSF measures than APOE ε4-carrier status and ε4 allele count. These findings were replicated in ADNI and observed in subsets of cognitively unimpaired (CU) participants. Discussion: The APOE-npscore reflects the genetic effect on neuropathology and provides an improved method to account for APOE in AD-related analyses.
| Type: | Article |
|---|---|
| Title: | Neuropathology-based APOE genetic risk score better quantifies Alzheimer's risk |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/alz.12990 |
| Publisher version: | https://doi.org/10.1002/alz.12990 |
| Language: | English |
| Additional information: | This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. See: http://creativecommons.org/licenses/by-nc/4.0/ |
| Keywords: | APOE, Alzheimer's disease, amyloid beta, biomarkers, cerebrospinal fluid endophenotypes, phosphorylated tau |
| 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 > Neurodegenerative Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10167143 |
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