AXA Research Fund & UPMC Chair, Sorbonne Universités, Université Pierre et Marie Curie (UPMC) Paris 06, Inserm, CNRS, Institut du Cerveau et de la Moelle Épinière (ICM), Département de Neurologie, Institut de la Mémoire et de la Maladie d'Alzheimer (IM2A), Hôpital Pitié-Salpêtrière, Boulevard de l'hôpital, F-75013 Paris, France; Laboratory of Alzheimer's Neuroimaging and Epidemiology, IRCCS Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
AXA Research Fund & UPMC Chair, Sorbonne Universités, Université Pierre et Marie Curie (UPMC) Paris 06, Inserm, CNRS, Institut du Cerveau et de la Moelle Épinière (ICM), Département de Neurologie, Institut de la Mémoire et de la Maladie d'Alzheimer (IM2A), Hôpital Pitié-Salpêtrière, Boulevard de l'hôpital, F-75013 Paris, France.
Neuroscience. 2017 Aug 15;357:119-133. doi: 10.1016/j.neuroscience.2017.05.048. Epub 2017 Jun 6.
The ε4 allelic variant of the Apolipoprotein E gene (APOE ε4) is the best-established genetic risk factor for late-onset Alzheimer's disease (AD). White matter (WM) microstructural damages measured with Diffusion Tensor Imaging (DTI) represent an early sign of fiber tract disconnection in AD. We examined the impact of APOE ε4 on WM microstructure in elderly individuals from the multicenter European DTI Study on Dementia. Voxelwise statistical analysis of fractional anisotropy (FA), mean diffusivity, radial and axial diffusivity (MD, radD and axD respectively) was carried out using Tract-Based Spatial Statistics. Seventy-four healthy elderly individuals - 31 APOE ε4 carriers (APOE ε4+) and 43 APOE ε4 non-carriers (APOE ε4-) -were considered for data analysis. All the results were corrected for scanner acquisition protocols, age, gender and for multiple comparisons. APOE ε4+ and APOE ε4- subjects were comparable regarding sociodemographic features and global cognition. A significant reduction of FA and increased radD was found in the APOE ε4+ compared to the APOE ε4- in the cingulum, in the corpus callosum, in the inferior fronto-occipital and in the inferior longitudinal fasciculi, internal and external capsule. APOE ε4+, compared to APOE ε4- showed higher MD in the genu, right internal capsule, superior longitudinal fasciculus and corona radiate. Comparisons stratified by center supported the results obtained on the whole sample. These findings support previous evidence in monocentric studies indicating a modulatory role of APOE ɛ4 allele on WM microstructure in elderly individuals at risk for AD suggesting early vulnerability and/or reduced resilience of WM tracts involved in AD.
载脂蛋白 E 基因（APOE ε4）的 ε4 等位基因变体是晚发性阿尔茨海默病（AD）最确定的遗传风险因素。用弥散张量成像（DTI）测量的白质（WM）微观结构损伤代表 AD 纤维束分离的早期迹象。我们检查了 APOE ε4 对来自多中心欧洲 DTI 痴呆研究的老年个体 WM 微观结构的影响。使用基于束的空间统计学对各向异性分数（FA）、平均扩散系数、径向和轴向扩散系数（MD、radD 和 axD 分别）进行了体素统计分析。对 74 名健康的老年个体 - 31 名 APOE ε4 携带者（APOE ε4+）和 43 名 APOE ε4 非携带者（APOE ε4-）进行了数据分析。所有结果均校正了扫描仪采集协议、年龄、性别和多重比较。APOE ε4+和 APOE ε4-受试者在社会人口统计学特征和整体认知方面具有可比性。与 APOE ε4-相比，APOE ε4+在扣带束、胼胝体、下额枕束和下纵束、内囊和外囊处的 FA 降低，radD 增加。与 APOE ε4-相比，APOE ε4+在膝部、右侧内囊、上纵束和放射冠显示出更高的 MD。按中心分层的比较支持了对整个样本的结果。这些发现支持了以前在单中心研究中的证据，表明 APOE ɛ4 等位基因对 AD 高危老年个体 WM 微观结构具有调节作用，表明 AD 相关 WM 束的早期脆弱性和/或恢复能力降低。
