Increased apolipoprotein E and decreased TNF‐α in the cerebrospinal fluid of nondemented APOE‐ε4 carriers

Abstract

Aim 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. Methods 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. Results CSF levels of apoE2, apoE3, and apoE4 were significantly higher (all nominal P < 10 × 10⁻⁵, false discovery rate < 0.001) and those of tumor necrosis factor‐α (TNF‐α) were significantly lower (nominal P = 1.39 × 10⁻⁶, 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. Conclusions Our findings indicate the possible roles of apoE and TNF‐α in the pathogenesis of APOE‐ε4‐associated Alzheimer's disease.