Cardiff University Brain Research Imaging Centre, School of Psychology, Cardiff University, Cardiff, Wales, UK.
German Center for Neurodegenerative Diseases (DZNE), Aging and Cognition Research Group, Magdeburg, Germany.
Neurobiol Aging. 2019 Jan;73:82-91. doi: 10.1016/j.neurobiolaging.2018.08.026. Epub 2018 Sep 22.
Young adult APOE-ε4 carriers show increased activity in posterior regions of the default mode network (pDMN), but how this is related to structural connectivity is unknown. Thirty young adults (one half of whom were APOE-ε4 carriers; mean age 20 years) were scanned using both diffusion and functional magnetic resonance imaging. The parahippocampal cingulum bundle (PHCB)-which links the pDMN and the medial temporal lobe-was manually delineated in individual participants using deterministic tractography. Measures of tract microstructure (mean diffusivity and fractional anisotropy) were then extracted from these tract delineations. APOE-ε4 carriers had lower mean diffusivity and higher fractional anisotropy relative to noncarriers in PHCB, but not in a control tract (the inferior longitudinal fasciculus). Furthermore, PHCB microstructure was selectively associated with pDMN (and medial temporal lobe) activity during a scene discrimination task known to be sensitive to Alzheimer's disease. These findings are consistent with a lifespan view of Alzheimer's disease risk, where early-life, connectivity-related changes in specific, vulnerable "hubs" (e.g., pDMN) lead to increased neural activity. Critically, such changes may reflect reduced network efficiency/flexibility in APOE-ε4 carriers, which in itself may portend a faster decline in connectivity over the lifespan and ultimately trigger early amyloid-β deposition in later life.
年轻的 APOE-ε4 携带者在后默认模式网络 (pDMN) 区域表现出更高的活动，但这与结构连接的关系尚不清楚。三十名年轻成年人（其中一半是 APOE-ε4 携带者；平均年龄 20 岁）使用扩散和功能磁共振成像进行了扫描。使用确定性轨迹追踪，在个体参与者中手动描绘了连接 pDMN 和内侧颞叶的后扣带束（PHCB）。然后，从这些轨迹描绘中提取轨迹微观结构（平均扩散度和各向异性分数）的度量。与非携带者相比，APOE-ε4 携带者在 PHCB 中的平均扩散度较低，各向异性分数较高，但在对照轨迹（下纵束）中则没有。此外，PHCB 微观结构与场景辨别任务期间的 pDMN（和内侧颞叶）活动选择性相关，该任务已知对阿尔茨海默病敏感。这些发现与阿尔茨海默病风险的终生观点一致，即特定的、脆弱的“枢纽”（例如，pDMN）在生命早期与连接相关的变化导致神经活动增加。关键的是，这种变化可能反映了 APOE-ε4 携带者中网络效率/灵活性的降低，这本身可能预示着在整个生命周期中连接更快下降，并最终导致晚年早期的淀粉样蛋白-β沉积。
