Proteins linking APOE ε4 with Alzheimer's disease

INTRODUCTION: The epsilon 4 allele of the apolipoprotein E gene (APOE epsilon 4) is the strongest genetic risk factor for Alzheimer's disease (AD), but the mechanisms connecting APOE epsilon 4 to AD are not clear. METHODS: Participants (n = 596) were from two clinical-pathological studies. Tissues from dorsolateral prefrontal cortex were examined to identify 8425 proteins. Post mortem pathological assessment used immunohistochemistry to obtain amyloid beta (A beta) load and tau tangle density. RESULTS: In separate models, APOE epsilon 4 was associated with 18 proteins, which were associated with A beta and tau tangles. Examining the proteins in a single model identified Netrin-1 and secreted frizzled-related protein 1 (SFRP1) as the two proteins linking APOE epsilon 4 with A beta with the largest effect sizes and Netrin-1 and testican-3 linking APOE epsilon 4 with tau tangles. DISCUSSION: We identified Netrin-1, SFRP1, and testican-3 as the most promising proteins that link APOE epsilon 4 with A beta and tau tangles.