One possible mechanism for the correlation between AD susceptibility and CD33 alleles is that the common CD33 risk allele, which preferentially gives rise to the long isoform (hCD33M), restrains phagocytosis in brain microglia, leading to the slow accumulation of aggregated amyloid-β peptides and thereby increasing the probability of neurodegenerative plaque deposition. This evidence concerns the gene CD33 and Alzheimer disease.