Browse by author
Lookup NU author(s): Dr Paul DonaghyORCiD, Professor Alan ThomasORCiD, Professor John O'Brien
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2025 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.INTRODUCTION: Lewy body dementia (LBD) shares genetic risk factors with Alzheimer's disease (AD), including apolipoprotein E (APOE), but is distinguishable at the genome-wide level. Polygenic risk scores (PRS) may therefore improve diagnostic classification. METHODS: We assessed diagnostic classification using AD-PRS excluding APOE (AD-PRSnoAPOE), APOE risk score (APOE-RS), and plasma phosphorylated tau 181 (p-tau181), in 83 participants with LBD, 27 with positron emission tomography amyloid beta (Aβ)positive mild cognitive impairment or AD (MCI+/AD), and 57 controls. RESULTS: Together AD-PRSnoAPOE and APOE-RS performed similarly to p-tau181 in discriminating MCI+/AD from controls (area under the curve 76% vs. 79%) and LBD (71% vs. 72%). In LBD, Aβ positivity was significantly associated with APOE-RS, but not with AD-PRSnoAPOE, or p-tau181. Combining AD-PRSnoAPOE, APOE-RS, and p-tau181 improved the discrimination of MCI+/AD from controls (81%) and LBD (75%), and the detection of Aβ in LBD (82%). DISCUSSION: Aβ deposition in LBD was associated with APOE, while MCI+/AD was also associated with AD-PRS beyond APOE. AD-PRS explains phenotypic variance not captured by APOE or p-tau181. Highlights: We investigated Alzheimer's disease (AD) polygenic risk score (PRS), apolipoprotein E (APOE), and plasma phosphorylated tau 181 (p-tau181) to classify AD and Lewy body dementia (LBD). AD-PRS with APOE achieved similar classification accuracy to p-tau181. AD-PRS without APOE significantly contributed to discriminating AD from LBD. Amyloid beta positivity in LBD was associated with APOE but not AD-PRS without APOE or p-tau181. Combining AD-PRS, APOE, and p-tau181 improved diagnostic classification accuracy.
Author(s): McKeever A, Swann P, Malpetti M, Donaghy PC, Thomas A, Mak E, Carter SF, Tan JHK, Hong YT, Fryer TD, Heslegrave A, Zetterberg H, Su L, Chouliaras L, Rowe JB, O'Brien JT
Publication type: Article
Publication status: Published
Journal: Alzheimer's and Dementia
Year: 2025
Volume: 21
Issue: 2
Print publication date: 01/02/2025
Online publication date: 24/01/2025
Acceptance date: 11/10/2024
Date deposited: 17/02/2025
ISSN (print): 1552-5260
ISSN (electronic): 1552-5279
Publisher: John Wiley and Sons Inc
URL: https://doi.org/10.1002/alz.14381
DOI: 10.1002/alz.14381
See more details
