APOE Genotype Testing
Genotyping the APOE gene, which has three common alleles (ε2, ε3, ε4). Carrying one or two copies of ε4 substantially raises lifetime risk of late-onset Alzheimer’s disease, and ε4 remains the strongest and most replicated common genetic risk factor for it. The difficulty is not the strength of that association. It is what an asymptomatic person is supposed to do with the result.
Mayeux R, Saunders AM, Shea S, et al. “Utility of the Apolipoprotein E Genotype in the Diagnosis of Alzheimer’s Disease.” N Engl J Med 1998;338:506–511 established APOE’s value alongside clinical assessment in symptomatic patients, where combining clinical diagnosis with genotype improved diagnostic accuracy (AUC 0.87) over clinical diagnosis alone (AUC 0.84). Predictive screening in an asymptomatic person is a different question. Since 2023–2024 APOE testing has acquired one specific new role: it is recommended before starting anti-amyloid therapies such as lecanemab for early Alzheimer’s disease, because ε4 carriers have both a different treatment-response profile and a higher risk of ARIA. Outside that pre-treatment context, or genetic counselling for a strong family history, no preventive intervention has been shown to change an asymptomatic ε4 carrier’s trajectory — and disclosure carries real, studied psychological and insurance or employment-related consequences.
Mayeux R, et al. N Engl J Med. 1998. PubMed: PMID 9468467