Borghesani Paul R, Johnson L Clark, Shelton Amy L, Peskind Elaine R, Aylward Elizabeth H, Schellenberg Gerard D, Cherrier Monique M
Mental Illness Research, Education, and Clinical Center (MIRECC), Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA.
Neurobiol Aging. 2008 Jul;29(7):981-91. doi: 10.1016/j.neurobiolaging.2007.01.012. Epub 2007 Mar 9.
The apolipoprotein varepsilon4 allele (APOE4) is a major genetic risk factor for Alzheimer's disease (AD) and has been associated with altered cortical activation as assessed by functional neuroimaging in cognitively normal younger and older carriers. We chose to evaluate medial temporal lobe (MTL) activation during encoding and recognition using a perspective-dependent (route or survey) visuospatial memory task by monitoring the blood-oxygen-level-dependent (BOLD) fMRI response in older, non-demented APOE4 carriers (APOE4+) and non-carriers (APOE4-). During encoding, the APOE4- group had greater average task-associated BOLD responses in ventral visual pathways, including the MTLs, as compared to the APOE4+ group. Furthermore, MTL activation was greater during route encoding than survey encoding on average in APOE4-, but not APOE4+, subjects. During recognition, both groups performed similarly and no BOLD signal differences were found. Finally, within-group analysis revealed MTL activation during encoding was correlated with recognition performance in APOE4-, but not APOE4+ subjects. Reduced task-associated MTL activation that does not correlate with either visuospatial perspective or task performance suggests that MTL dysregulation occurs prior to clinical symptoms of dementia in APOE*4 carriers.
载脂蛋白ε4等位基因（APOE4）是阿尔茨海默病（AD）的主要遗传风险因素，在认知正常的年轻和老年携带者中，通过功能神经影像学评估发现它与皮质激活改变有关。我们选择通过监测老年非痴呆APOE4携带者（APOE4+）和非携带者（APOE4-）的血氧水平依赖（BOLD）功能磁共振成像（fMRI）反应，使用视角依赖（路线或俯瞰）视觉空间记忆任务来评估编码和识别过程中的内侧颞叶（MTL）激活。在编码过程中，与APOE4+组相比，APOE4-组在包括MTL在内的腹侧视觉通路中具有更大的平均任务相关BOLD反应。此外，平均而言，在APOE4-受试者中，路线编码期间的MTL激活大于俯瞰编码期间的激活，但在APOE4+受试者中并非如此。在识别过程中，两组表现相似，未发现BOLD信号差异。最后，组内分析显示，在APOE4-受试者中，编码期间的MTL激活与识别表现相关，但在APOE4+受试者中并非如此。与视觉空间视角或任务表现均无关的任务相关MTL激活减少表明，APOE*4携带者在痴呆临床症状出现之前就发生了MTL失调。
