APP and Alzheimer disease: PSEN1 mutations account for ~81% of FD cases, APP accounts for ~14%, and PSEN2 accounts for ~6%.11 In addition to these three genes (APP, PSEN1, and PSEN2), more than 20 genetic risk loci for AD have been identified.16,17 The strongest genetic risk factor for AD is the ε4 allele of apolipoprotein E (APOE).18–21APOE is a class of proteins involved in lipid metabolism and is immunochemically colocalized to senile plaques, vascular amyloid deposits, and NFTs in AD.