Department of Mental Disorder Research, National Center of Neurology and Psychiatry, National Institute of Neuroscience, Kodaira, Japan.
Department of Psychiatry, Shinshu University School of Medicine, Matsumoto, Japan.
Neuropsychopharmacol Rep. 2020 Jun;40(2):201-205. doi: 10.1002/npr2.12110. Epub 2020 May 19.
The ε4 allele of apolipoprotein E gene (APOE) is a well-known risk factor of late-onset Alzheimer's disease. However, little is known why this variant confers a risk for Alzheimer's disease. The aim of this study was to examine the influence of the APOE genotype on cerebrospinal fluid (CSF) protein levels.
The present study performed a secondary analysis on our previously generated database to compare the CSF levels of 1128 proteins between APOE-ε4 carriers (28 subjects) and noncarriers (104 subjects). All subjects were physically healthy Japanese individuals without dementia.
CSF levels of apoE2, apoE3, and apoE4 were significantly higher (all nominal P < 10 × 10 , false discovery rate < 0.001) and those of tumor necrosis factor-α (TNF-α) were significantly lower (nominal P = 1.39 × 10 , false discovery rate < 0.001) in APOE-ε4 carriers than in noncarriers. No significant correlation was observed between the CSF levels of TNF-α and any of the apoE proteins.
Our findings indicate the possible roles of apoE and TNF-α in the pathogenesis of APOE-ε4-associated Alzheimer's disease.
载脂蛋白 E 基因（APOE）的 ε4 等位基因是晚发性阿尔茨海默病的一个众所周知的危险因素。然而，人们对为什么这种变体导致阿尔茨海默病风险知之甚少。本研究旨在研究 APOE 基因型对脑脊液（CSF）蛋白水平的影响。
本研究对我们之前生成的数据库进行了二次分析，以比较 APOE-ε4 携带者（28 例）和非携带者（104 例）之间的 1128 种蛋白质的 CSF 水平。所有受试者均为无痴呆的身体健康的日本个体。
APOE-ε4 携带者的 apoE2、apoE3 和 apoE4 水平显著升高（所有名义 P<10×10，错误发现率<0.001），肿瘤坏死因子-α（TNF-α）水平显著降低（名义 P=1.39×10，错误发现率<0.001）。TNF-α与任何 apoE 蛋白的 CSF 水平之间均无显著相关性。
我们的研究结果表明 apoE 和 TNF-α 可能在 APOE-ε4 相关的阿尔茨海默病发病机制中发挥作用。
