Mooney Katelyn E, Archer Derek B, Sathe Aditi, Hohman Timothy J, Kadiri Ose, Lamar Melissa, Arfanakis Konstantinos, Yu Lei, Barnes Lisa L, Deters Kacie D
University of California Los Angeles, Neuroscience Interdepartmental Program (NSIDP), David Geffen School of Medicine Los Angeles California USA.
Department of Integrative Biology and Physiology University of California Los Angeles Los Angeles California USA.
Alzheimers Dement (Amst). 2025 Apr 6;17(2):e70099. doi: 10.1002/dad2.70099. eCollection 2025 Apr-Jun.
We assessed associations between apolipoprotein E Translocase of Outer Mitochondrial Membrane 40 (-'523 haplotypes and white matter microstructure (WMM) across limbic tracts important for memory and cognition in non-Hispanic Black and White individuals.
Linear regression models, stratified by and racialized groups, assessed associations between -'523-S and limbic tract WMM free-water (FW) and free-water-corrected fractional anisotropy (FAFWcorr).
Black-ε4+-one-'523-S carriers had lower FW in the cingulum and inferior longitudinal fasciculus compared to Black-ε4+-no-'523-S carriers. Additionally, Black-ε4+-one-'523-S carriers had lower FW in the cingulum, uncinate, and fornix, and higher FA in the uncinate compared to Black-ε4+-'523-S/S carriers. White-ε3/ε3-'523-S/S carriers had lower FAFWcorr in the cingulum and inferior temporal gyrus compared to White-ε3/ε3-no-'523-S carriers, and lower FAFWcorr in the cingulum compared to White-ε3/ε3-one-'523-S carriers.
This supports prior work that '523-S is associated with abnormal aging in White-ε3/ε3 carriers, but is potentially risk-mitigating in Black-ε4+ carriers, while suggesting a differential effect by racialized background of on WMM.
White matter microstructure (WMM) across limbic tracts important for cognition was measured by diffusion MRI.Black apolipoprotein E (APOE) ε4+ carriers with one copy of TOMM40-'523-S had normal aging WMM metrics across several tracts, including the cingulum bundle, uncinate fasciculus, fornix, and inferior longitudinal fasciculus.White APOE ε3/ε3 carriers with two copies of TOMM40-'523-S had abnormal aging WMM metrics in the cingulum bundle and inferior temporal gyrus.APOE associations with aging may differ in racialized groups due to TOMM40-'523-S copy number.
我们评估了非裔美国人和白人个体中，线粒体外膜载脂蛋白E转位酶40（TOMM40）-523单倍型与对记忆和认知至关重要的边缘系统白质微观结构（WMM）之间的关联。
采用按年龄和种族分组的线性回归模型，评估TOMM40-523-S与边缘系统白质微观结构的自由水（FW）和自由水校正分数各向异性（FAFWcorr）之间的关联。
与携带TOMM40-523-S阴性的非裔美国ε4+携带者相比，携带一个TOMM40-523-S拷贝的非裔美国ε4+携带者在扣带束和下纵束中的自由水含量较低。此外，与携带两个TOMM40-523-S拷贝的非裔美国ε4+携带者相比，携带一个TOMM40-523-S拷贝的非裔美国ε4+携带者在扣带束、钩束和穹窿中的自由水含量较低，在钩束中的分数各向异性较高。与携带TOMM40-523-S阴性的白人ε3/ε3携带者相比，携带两个TOMM40-523-S拷贝的白人ε3/ε3携带者在扣带束和颞下回中的FAFWcorr较低，与携带一个TOMM40-523-S拷贝的白人ε3/ε3携带者相比，其在扣带束中的FAFWcorr也较低。
这支持了之前的研究结果，即TOMM40-523-S与白人ε3/ε3携带者的异常衰老有关，但在非裔美国ε4+携带者中可能具有减轻风险的作用，同时表明种族背景对WMM有不同的影响。
通过扩散MRI测量了对认知至关重要的边缘系统白质微观结构（WMM）。携带一个TOMM40-523-S拷贝的非裔美国载脂蛋白E（APOE）ε4+携带者在包括扣带束、钩束、穹窿和下纵束在内的多个区域具有正常衰老的WMM指标。携带两个TOMM40-523-S拷贝的白人APOEε3/ε3携带者在扣带束和颞下回中具有异常衰老的WMM指标。由于TOMM40-523-S拷贝数的不同，APOE与衰老的关联在不同种族群体中可能存在差异。
