Despite this strong association with pathology, the gene–gene interaction between CD33 and PTPN6 did not influence cognitive decline, TDP43, hippocampal sclerosis, and clinical diagnosis of AD, supporting the complexity of AD and microglial genes, as well as the concept that AD pathology is more than the buildup of amyloid plaques and tau tangles. The gene discussed is CD33; the disease is Alzheimer disease.