Stanford University School of Medicine, Department of Neurology and Neurological Sciences, Stanford, California, USA.
Rush University Medical Center, Department of Neurological Sciences, Rush Alzheimer's Disease Center, Chicago, Illinois, USA.
Alzheimers Dement. 2021 Aug;17(8):1287-1296. doi: 10.1002/alz.12295. Epub 2021 Feb 13.
The goal was to investigate effects of APOE-TOMM40-'523 haplotypes on cognitive decline in non-demented non-Hispanic Blacks (NHB), and determine whether effects differ from non-Hispanic Whites (NHW).
The impact of zero to two copies of the '523-Short variant (S; poly-T alleles < 20) within apolipoprotein E (APOE) genotype on a composite measure of global cognition and five domains was examined.
In NHB with ε3/ε3 (N = 294), '523-S/S was associated with faster decline in global cognition (β = -0.048, P = 0.017), episodic memory (β = -0.05, P = 0.031), and visuospatial ability (β = -0.037, P = 0.034) relative to those without '523-S. For NHB ε4+ (N = 182), '523-S/S had slower decline in global cognition (β = 0.047, P = 0.042) and visuospatial ability (β = 0.07, P = 0.0005) relative to '523-S non-carriers. NHB ε4+ with '523-S also had a slower rate of decline than NHWs ε4+ with '523-S.
'523-S/S has a different effect on cognitive decline among NHB dependent on APOE allele. Differences in the effect of ε4-'523-S in NHB may explain prior mixed findings on ε4 and decline in this population.
本研究旨在探讨 APOE-TOMM40-“523”单倍型对非痴呆非西班牙裔黑人(NHB)认知能力下降的影响,并确定其影响是否与非西班牙裔白人(NHW)不同。
研究分析了载脂蛋白 E(APOE)基因型中零至两个“523-短变体(S;多态 T 等位基因<20)”对整体认知和五个认知领域的复合指标的影响。
在 APOE ε3/ε3 的 NHB 中(N=294),“523-S/S”与全球认知(β=-0.048,P=0.017)、情景记忆(β=-0.05,P=0.031)和视空间能力(β=-0.037,P=0.034)的下降速度更快,而与不携带“523-S”的人群相比。对于 NHB ε4+(N=182),“523-S/S”与全球认知(β=0.047,P=0.042)和视空间能力(β=0.07,P=0.0005)的下降速度较慢,而与“523-S”非携带者相比。与 NHW ε4+的“523-S”携带者相比,NHB ε4+的“523-S”携带者认知下降速度也较慢。
“523-S/S”对 NHB 认知下降的影响取决于 APOE 等位基因,这与先前关于该人群中 ε4 和下降的混合结果一致。