Refining Risk for Alzheimer's Disease Among Heterozygous APOE ε4 Carriers

被引:4
作者
Patel, Smita [1 ]
Wei, Jun [2 ]
Shi, Zhuqing [2 ]
Rifkin, Andrew S. [2 ]
Zheng, S. Lilly [2 ]
Gelfman, Elizabeth [3 ]
Duggan, David [4 ]
Helfand, Brian T. [2 ,5 ]
Hulick, Peter J. [6 ]
Xu, Jianfeng [2 ,5 ]
机构
[1] NorthShore Univ HlthSyst, Dept Neurol, Evanston, IL USA
[2] NorthShore Univ HlthSyst, Program Personalized Canc Care, Evanston, IL USA
[3] Northwestern Feinberg Sch Med, Chicago, IL USA
[4] City Hope Natl Med Ctr, Translat Genom Res Inst, Phoenix, AZ USA
[5] Univ Chicago, Pritzker Sch Med, Chicago, IL USA
[6] NorthShore Univ HlthSyst, Neaman Ctr Personalized Med, Evanston, IL USA
关键词
Alzheimer's disease; APOE; genetic counseling; polygenic risk score; UK Biobank; APOLIPOPROTEIN-E; DISCLOSURE; GENOTYPE;
D O I
10.3233/JAD-230156
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
In a large population-based cohort, we show not all heterozygous APOE epsilon 4 carriers are at increased risk for Alzheimer's disease (AD); a significantly higher AD proportion was only found for epsilon 3/epsilon 4, not epsilon 2/epsilon 4. Among epsilon 3/epsilon 4 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 epsilon 4 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.
引用
收藏
页码:483 / 489
页数:7
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