Department of Health and Biomedical Sciences, College of Health Professions, University of Texas Rio Grande Valley, Brownsville, TX, 78520, USA.
Department of STEM, School of Arts and Sciences, Regis College, Weston, MA, 02493, USA.
Neurol Sci. 2024 Mar;45(3):1041-1050. doi: 10.1007/s10072-023-07076-1. Epub 2023 Sep 28.
The Apolipoprotein E (APOE) ε4 allele is a risk factor for late-onset Alzheimer's disease (AD). However, no investigation has focused on racial differences in the longitudinal effect of APOE genotypes on CSF amyloid beta (Aβ42) and tau levels in AD.
This study used data from the Alzheimer's Disease Neuroimaging Initiative (ADNI): 222 participants with AD, 264 with cognitive normal (CN), and 692 with mild cognitive impairment (MCI) at baseline and two years follow-up. We used a linear mixed model to investigate the effect of APOE-ε4-genotypes on longitudinal changes in the amyloid beta and tau levels.
Individuals with 1 or 2 APOE ε4 alleles revealed significantly higher t-Tau and p-Tau, but lower amyloid beta Aβ42 compared with individuals without APOE ε4 alleles. Significantly higher levels of log-t-Tau, log-p-Tau, and low levels of log-Aβ42 were observed in the subjects with older age, being female, and the two diagnostic groups (AD and MCI). The higher p-Tau and Aβ42 values are associated with poor Mini-Mental State Examination (MMSE) performance. Non-Hispanic Africa American (AA) and Hispanic participants were associated with decreased log-t-Tau levels (β = - 0.154, p = 0.0112; β = - 0.207, and p = 0.0016, respectively) as compared to those observed in Whites. Furthermore, Hispanic participants were associated with a decreased log-p-Tau level (β = - 0.224, p = 0.0023) compared to those observed in Whites. There were no differences in Aβ42 level for non-Hispanic AA and Hispanic participants compared with White participants.
Our study, for the first time, showed that the APOE ε4 allele was associated with these biomarkers, however with differing degrees among racial groups.
载脂蛋白 E（APOE）ε4 等位基因是晚发性阿尔茨海默病（AD）的危险因素。然而，目前尚无研究关注 APOE 基因型对 AD 患者脑脊液淀粉样蛋白β（Aβ42）和 tau 水平的纵向影响的种族差异。
本研究使用了来自阿尔茨海默病神经影像学倡议（ADNI）的数据：222 名 AD 患者、264 名认知正常（CN）患者和 692 名轻度认知障碍（MCI）患者在基线和两年随访时进行了研究。我们使用线性混合模型来研究 APOE-ε4 基因型对淀粉样蛋白β和 tau 水平的纵向变化的影响。
携带 1 或 2 个 APOE ε4 等位基因的个体与不携带 APOE ε4 等位基因的个体相比，tau 蛋白（t-Tau）和磷酸化 tau 蛋白（p-Tau）水平显著升高，但 Aβ42 水平显著降低。在年龄较大、女性和 AD 及 MCI 两种诊断组的受试者中，log-t-Tau、log-p-Tau 水平更高，而 Aβ42 水平更低。较高的 p-Tau 和 Aβ42 值与较差的简易精神状态检查（MMSE）表现相关。与白人相比，非裔美国人和西班牙裔参与者的 log-t-Tau 水平降低（β= -0.154，p= 0.0112；β= -0.207，p= 0.0016）。此外，与白人相比，西班牙裔参与者的 log-p-Tau 水平降低（β= -0.224，p= 0.0023）。非裔美国人和西班牙裔参与者的 Aβ42 水平与白人参与者无差异。
我们的研究首次表明，APOE ε4 等位基因与这些生物标志物相关，但在不同种族群体中程度不同。
