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.
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This post is Copyright: Anna McKeever,
Peter Swann,
Maura Malpetti,
Paul C. Donaghy,
Alan Thomas,
Elijah Mak,
Stephen F. Carter,
Jerry H. K. Tan,
Young T. Hong,
Tim D. Fryer,
Amanda Heslegrave,
Henrik Zetterberg,
Li Su,
Leonidas Chouliaras,
James B. Rowe,
John T. O’Brien | January 24, 2025