Functional studies suggest that ABCA1 deficiency increases Aβ deposition and exacerbates cognitive impairment in mice, especially in those expressing APOE-ε4 [114], so the protective effect may be mediated by increased expression of ABCA1 or a gain-of-function in ABCA1 protein leading to enhanced lipidation of APOE. This evidence concerns the gene APOE and Cognitive impairment.