多基因风险可区分路易体痴呆与阿尔茨海默病。

Polygenic risk discriminates Lewy body dementia from Alzheimer's disease.

作者信息

McKeever Anna, Swann Peter, Malpetti Maura, Donaghy Paul C, Thomas Alan, Mak Elijah, Carter Stephen F, Tan Jerry H K, Hong Young T, Fryer Tim D, Heslegrave Amanda, Zetterberg Henrik, Su Li, Chouliaras Leonidas, Rowe James B, O'Brien John T

机构信息

Department of Psychiatry, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, UK.

Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK.

出版信息

Alzheimers Dement. 2025 Feb;21(2):e14381. doi: 10.1002/alz.14381. Epub 2025 Jan 24.

DOI:10.1002/alz.14381

PMID:39853853

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11848393/

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-PRS ), 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-PRS 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-PRS , or p-tau181. Combining AD-PRS , 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.

摘要

引言

路易体痴呆（LBD）与阿尔茨海默病（AD）具有共同的遗传风险因素，包括载脂蛋白E（APOE），但在全基因组水平上可区分。因此，多基因风险评分（PRS）可能会改善诊断分类。

方法

我们使用排除APOE的AD-PRS、APOE风险评分（APOE-RS）和血浆磷酸化tau 181（p-tau181）对83名LBD患者、27名正电子发射断层扫描淀粉样β蛋白（Aβ）阳性的轻度认知障碍或AD（MCI+/AD）患者以及57名对照者进行诊断分类评估。

结果

AD-PRS和APOE-RS在区分MCI+/AD与对照者（曲线下面积分别为76%和79%）以及LBD（71%和72%）方面表现与p-tau181相似。在LBD中，Aβ阳性与APOE-RS显著相关，但与AD-PRS或p-tau181无关。将AD-PRS、APOE-RS和p-tau181结合起来可提高区分MCI+/AD与对照者（81%）以及LBD（75%）的能力，以及检测LBD中Aβ的能力（82%）。

讨论

LBD中的Aβ沉积与APOE相关，而MCI+/AD除了与APOE相关外还与AD-PRS相关。AD-PRS解释了APOE或p-tau181未捕捉到的表型变异。

要点

我们研究了阿尔茨海默病（AD）多基因风险评分（PRS）、载脂蛋白E（APOE）和血浆磷酸化tau 181（p-tau181）以对AD和路易体痴呆（LBD）进行分类。含APOE的AD-PRS与p-tau181具有相似的分类准确性。不含APOE的AD-PRS对区分AD与LBD有显著贡献。LBD中的淀粉样β蛋白阳性与APOE相关，但与不含APOE的AD-PRS或p-tau181无关。结合AD-PRS、APOE和p-tau181可提高诊断分类准确性。