In our functional dissection of the CD33 Alzheimer's disease susceptibility locus, we found that the rs3865444C risk allele was associated with greater cell surface expression of CD33 in the monocytes (t50 = 10.06, Pjoint = 1.3 × 10−13) of young and older individuals. It was also associated with diminished internalization of amyloid-β 42 peptide, accumulation of neuritic amyloid pathology and fibrillar amyloid on in vivo imaging, and increased numbers of activated human microglia.
