AD is pathologically characterized by the formation of intracellular neurofibrillary tangles (NFTs), comprised of hyperphosphorylated tau protein, and extracellular amyloid plaques, comprised of amyloid-beta (Aβ) peptides1. Apolipoprotein (apo) E4, the major genetic risk factor for AD3,4, is found to be associated with increases in both pathologies1. In general, apoE4 increases AD risk and lowers the age of onset in a gene-dose dependent manner5. Remarkably, the lifetime risk estimate of developing AD by age 85 is ~65% in people with two copies of the apoE4 allele but only ~10% in people with two copies of the apoE3 allele6. This striking difference highlights the importance of apoE4 in the pathogenesis of AD.
