在载脂蛋白 E ɛ4 杂合子携带者中细化阿尔茨海默病的风险。

Refining Risk for Alzheimer's Disease Among Heterozygous APOEɛ4 Carriers.

机构信息

Department of Neurology, NorthShore University HealthSystem, Evanston, IL, USA.

Program for Personalized Cancer Care, NorthShore University HealthSystem, Evanston, IL, USA.

出版信息

J Alzheimers Dis. 2023;94(2):483-489. doi: 10.3233/JAD-230156.

DOI:10.3233/JAD-230156

PMID:37334598

Abstract

In a large population-based cohort, we show not all heterozygous APOEɛ4 carriers are at increased risk for Alzheimer's disease (AD); a significantly higher AD proportion was only found for ɛ3/ɛ4, not ɛ2/ɛ4. Among ɛ3/ɛ4 carriers (24% in the cohort), the AD proportion differed considerably by polygenic risk score (PRS). In particular, the AD proportion was lower than the entire cohort for subjects in the bottom 20-percentile PRS and was higher than that of homozygous ɛ4 carriers for subjects at the top 5th-percentile PRS. Family history was no longer a significant predictor of AD risk after adjusting APOE and PRS.

摘要

在一项大型基于人群的队列研究中，我们发现并非所有杂合子 APOEɛ4 携带者都具有更高的阿尔茨海默病（AD）风险；仅发现ɛ3/ɛ4 携带者的 AD 比例明显更高，而ɛ2/ɛ4 携带者则不然。在ɛ3/ɛ4 携带者（队列中占 24%）中，AD 比例因多基因风险评分（PRS）而异。特别是，对于 PRS 处于后 20%分位数的受试者，AD 比例低于整个队列，而对于 PRS 处于前 5%分位数的受试者，AD 比例则高于纯合子ɛ4 携带者。调整 APOE 和 PRS 后，家族史不再是 AD 风险的显著预测因素。