Department of Neurology, NorthShore University HealthSystem, Evanston, IL, USA.
Program for Personalized Cancer Care, NorthShore University HealthSystem, Evanston, IL, USA.
J Alzheimers Dis. 2023;94(2):483-489. doi: 10.3233/JAD-230156.
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.
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。
