APOE and early-onset autosomal dominant Alzheimer disease: For instance, the APOE gene has been well identified to be associated with Alzheimer’s disease from large scale GWAS [2–5], one possible explanation is that the SNP variant in APOE can first regulate the APOE gene expression [6–10], then act on the production of amyloid plaques and neurofibrillary tangles, and finally lead to AD [11–13].