Abstract
Alzheimers Dement. 2025 Jan 24:e14381. doi: 10.1002/alz.14381. Online ahead of print.
ABSTRACT
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-PRSno APOE), 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-PRSno APOE 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-PRSno APOE, or p-tau181. Combining AD-PRSno APOE, 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.
PMID:39853853 | DOI:10.1002/alz.14381
UK DRI Authors
