The fundamental biological influences on brain Aβ levels are not yet fully understood. The strongest known genetic risk factor for AD is presence of the apolipoprotein E (APOE) ε4 allele,7 and in vitro and murine studies have proposed plausible links between the encoded ApoE E4 isoform and aberrant Aβ mechanisms.8 However, APOE ε4 is neither necessary nor sufficient for development of AD pathology, suggesting that the biology underlying Aβ accumulation involves contributions from other genes and pathways, as well as the environment.
