Taylor Joy L, Scanlon Blake K, Farrell Michelle, Hernandez Beatriz, Adamson Maheen M, Ashford J Wesson, Noda Art, Murphy Greer M, Weiner Michael W
Veterans Affairs Palo Alto Health Care System, Sierra-Pacific MIRECC, Palo Alto CA, USA; Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Veterans Affairs Palo Alto Health Care System, Sierra-Pacific MIRECC, Palo Alto CA, USA; Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Neurobiol Aging. 2014 Nov;35(11):2479-2485. doi: 10.1016/j.neurobiolaging.2014.05.011. Epub 2014 May 15.
Atrophy of the hippocampus and surrounding temporal regions occurs in Alzheimer's disease (AD). APOE ε4, the major genetic risk factor for late-onset AD, has been associated with smaller volume in these regions before amyloidosis can be detected by AD biomarkers. To examine APOE ε4 effects in relation to aging, we performed a longitudinal magnetic resonance imaging study involving cognitively normal adults (25 APOE ε4 carriers and 31 ε3 homozygotes), initially aged 51-75 years. We used growth curve analyses, which can provide information about APOE ε4-related differences initially and later in life. Hippocampal volume was the primary outcome; nearby medial temporal regions were secondary outcomes. Brain-derived neurotrophic factor, val66met was a secondary covariate. APOE ε4 carriers had significantly smaller initial hippocampal volumes than ε3 homozygotes. Rate of hippocampal atrophy was not greater in the APOE ε4 group, although age-related atrophy was detected in the overall sample. The findings add to the growing evidence that effects of APOE ε4 on hippocampal size begin early in life, underscoring the importance of early interventions to increase reserve.
海马体及周围颞叶区域萎缩在阿尔茨海默病（AD）中会出现。APOE ε4是晚发型AD的主要遗传风险因素，在AD生物标志物检测到淀粉样变性之前，该区域体积较小就与之相关。为了研究APOE ε4与衰老相关的影响，我们对认知正常的成年人（25名APOE ε4携带者和31名ε3纯合子）进行了一项纵向磁共振成像研究，他们最初年龄在51至75岁之间。我们采用生长曲线分析，其可以提供有关APOE ε4相关差异在生命早期和晚期的信息。海马体体积是主要研究结果；附近的内侧颞叶区域是次要研究结果。脑源性神经营养因子val66met是次要协变量。APOE ε4携带者的初始海马体体积显著小于ε3纯合子。尽管在整个样本中检测到与年龄相关的萎缩，但APOE ε4组的海马体萎缩率并不更高。这些发现进一步证明了APOE ε4对海马体大小的影响在生命早期就已开始，强调了早期干预以增加储备的重要性。
