From the Departments of Neurology and Neurological Sciences (G.A.K., D.B., J.C.S., J.D.B., M.C.F., G.K.D., T.W.-C.) and Radiology (B.K.R.), Stanford University School of Medicine, Stanford; and Center for Tissue Regeneration, Repair and Restoration (T.W.-C.), Veterans Affairs Palo Alto Health Care System, Palo Alto, CA.
Neurology. 2014 Feb 25;82(8):691-7. doi: 10.1212/WNL.0000000000000154. Epub 2014 Jan 22.
Using high-resolution structural MRI, we endeavored to study the relationships among APOE ε4, hippocampal subfield and stratal anatomy, and episodic memory.
Using a cross-sectional design, we studied 11 patients with Alzheimer disease dementia, 14 patients with amnestic mild cognitive impairment, and 14 age-matched healthy controls with no group differences in APOE ε4 carrier status. Each subject underwent ultra-high-field 7.0-tesla MRI targeted to the hippocampus and neuropsychological assessment.
We found a selective, dose-dependent association of APOE ε4 with greater thinning of the CA1 apical neuropil, or stratum radiatum/stratum lacunosum-moleculare (CA1-SRLM), a hippocampal subregion known to exhibit early vulnerability to neurofibrillary pathology in Alzheimer disease. The relationship between the ε4 allele and CA1-SRLM thinning persisted after controlling for dementia severity, and the size of other hippocampal subfields and the entorhinal cortex did not differ by APOE ε4 carrier status. Carriers also exhibited worse episodic memory function but similar performance in other cognitive domains compared with noncarriers. In a statistical mediation analysis, we found support for the hypothesis that CA1-SRLM thinning may link the APOE ε4 allele to its phenotypic effects on memory.
The APOE ε4 allele segregated dose-dependently and selectively with CA1-SRLM thinning and worse episodic memory performance in a pool of older subjects across a cognitive spectrum. These findings highlight a possible role for this gene in influencing a critical hippocampal subregion and an associated symptomatic manifestation.
使用高分辨率结构 MRI，我们试图研究 APOE ε4 与海马亚区和层状解剖结构以及情景记忆之间的关系。
采用横断面设计，我们研究了 11 例阿尔茨海默病痴呆患者、14 例遗忘型轻度认知障碍患者和 14 例年龄匹配的无 APOE ε4 携带状态组间差异的健康对照者。每位受试者均接受超高场 7.0 特斯拉 MRI 海马区靶向扫描和神经心理学评估。
我们发现 APOE ε4 与 CA1 顶端神经突或放射层/腔隙状分子层（CA1-SRLM）变薄呈选择性、剂量依赖性相关，CA1-SRLM 是阿尔茨海默病神经纤维病理早期易损的海马亚区。在控制痴呆严重程度后，ε4 等位基因与 CA1-SRLM 变薄之间的关系仍然存在，并且其他海马亚区和内嗅皮层的大小不受 APOE ε4 携带状态的影响。携带者的情景记忆功能也较差，但与非携带者相比，其他认知领域的表现相似。在统计中介分析中，我们支持假说，即 CA1-SRLM 变薄可能将 APOE ε4 等位基因与其对记忆的表型效应联系起来。
在认知谱上的一组老年受试者中，APOE ε4 等位基因与 CA1-SRLM 变薄和情景记忆功能下降呈剂量依赖性和选择性分离。这些发现强调了该基因在影响关键海马亚区和相关症状表现方面的可能作用。
