C. Reassure and address patient’s concerns and follow up in 1 year.
Most cases of Alzheimer disease are sporadic and are thought to be influenced by multiple heritable and nonheritable factors. The APOE gene (19q32.13) codes for apolipoprotein E and has 3 common isoforms (ɛ2, ɛ3, and ɛ4) defined by specific base-pair variations (ie, single-nucleotide variations [SNVs]). APOE ɛ3 is the most common allele (worldwide prevalence, 78%) and has no association with Alzheimer disease risk.1 While APOE ɛ2 (worldwide prevalence, 8%) is associated with a lower rate of Alzheimer disease (odds ratio [OR], 0.6 vs ɛ3/ɛ3), APOE ɛ4 (14%) is the strongest known genetic susceptibility factor for sporadic Alzheimer disease (OR, 8-12 for ɛ4/ɛ4 vs ɛ3/ɛ3; Table)2,3 and is associated with reduced age of Alzheimer disease onset by approximately 2.5 years per allele copy.4 The main function of apolipoprotein E is mediating extracellular lipid transport and cellular lipid uptake, the latter through a process known as endocytosis. Although its precise role in Alzheimer disease pathophysiology is unclear, proposed mechanisms for APOE ɛ4 include promoting amyloid deposition, impairing amyloid clearance via modulating the activity of macrophages known as microglia, and influencing synaptic plasticity, defined as the ability to change the strength of connections between neurons.1