APOA1 and Alzheimer disease: Mechanistically, preclinical studies show that HDL-deficient AD mice, generated by genetic deletion of apoA-I, have increased vascular Aβ deposition, known as CAA, and worse cognitive performance compared to AD mice with normal HDL levels [10], whereas AD mice overexpressing apoA-I from its native promoter show the opposite phenotype with an additional improvement in central nervous system (CNS) inflammation [11].