CD33 Alzheimer's disease locus: altered monocyte function and amyloid biology

Genome-wide association studies have identified CD33 as an Alzheimer's disease susceptibility locus. Here, the authors show that the CD33 risk allele is associated with altered myeloid function, microglial activation and in vivo amyloid pathology. In our functional dissection of the CD33 Alzheimer's disease susceptibility locus, we found that the rs3865444 C risk allele was associated with greater cell surface expression of CD33 in the monocytes ( t 50 = 10.06, P joint = 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.