Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA.
Alzheimers Dement. 2023 Mar;19(3):784-796. doi: 10.1002/alz.12711. Epub 2022 Jun 12.
Apolipoprotein E (APOE) ε4 is an important genetic risk factor for typical Alzheimer's disease (AD), influencing brain volume and tau burden. Little is known about its influence in atypical presentations of AD.
An atypical AD cohort of 140 patients diagnosed with either posterior cortical atrophy or logopenic progressive aphasia underwent magnetic resonance imaging and positron emission tomography. Linear mixed effects models were fit to assess the influence of APOE ε4 on cross-sectional and longitudinal regional metrics.
At baseline, APOE ε4 carriers had smaller hippocampal and amygdala volumes and greater tau standardized uptake volume ratio in the hippocampus and entorhinal cortex compared to non-carriers while longitudinally, APOE ε4 non-carriers showed faster rates of atrophy and tau accumulation in the entorhinal cortex, with faster tau accumulation in the hippocampus.
APOE ε4 influences patterns of neurodegeneration and tau deposition and was associated with more medial temporal involvement, although there is evidence that non-carriers may be catching up over time.
载脂蛋白 E (APOE) ε4 是典型阿尔茨海默病 (AD) 的重要遗传风险因素，影响脑容量和 tau 负担。但其在非典型 AD 表现中的影响知之甚少。
对诊断为后部皮质萎缩或失语法性进行性失语症的 140 例非典型 AD 患者进行磁共振成像和正电子发射断层扫描。采用线性混合效应模型评估 APOE ε4 对横断面和纵向区域指标的影响。
基线时，与非携带者相比，APOE ε4 携带者的海马体和杏仁核体积较小，海马体和内嗅皮层的 tau 标准化摄取比值较高；而在纵向研究中，APOE ε4 非携带者的内嗅皮层萎缩和 tau 积累速度更快，海马体的 tau 积累速度也更快。
APOE ε4 影响神经退行性变和 tau 沉积模式，与内侧颞叶受累更为相关，尽管有证据表明，非携带者可能随着时间的推移逐渐赶上。
