Table 1.

APOE variants and key AD-related clinical features

APOE allelic variant	Allele frequency in cognitively healthy individuals (%)286	Allele frequency in patients with AD (%)286	Odds ratio for AD development286	Key clinical features
APOE*ε2	7	4	0.621	Associated with a reduced risk of AD6–9 Associated with slower cognitive decline during ageing, even after adjustment for amyloid-β pathologies87 Associated with an increased risk of cerebral amyloid angiopathy (CAA) and CAA-related intracerebral haemorrhage70–73 Contributes to the onset of type III hyperlipoproteinaemia22,56 Associated with increased tau pathology in progressive supranuclear palsy122
APOE*ε3	79	58	1.000	The most common APOE allele APOE*ε3/ε3 is considered to be a reference genotype in most studies
APOE*ε4	14	38	3.680	Associated with increased risk of both early-onset9 (Box 2) and late-onset AD4–6,8,9 Shifts the onset of AD to 2–5 or 5–10 years earlier depending on APOE*ε4 allele number4,10 Seems to interact with sex to modify AD risk (Box 3)6,8,297 Associated with pro-atherogenic changes in lipoprotein distribution56 Associated with an increased risk of CAA67,68 Associated with increased tau pathology in AD65 Associated with increased risk of dementia with Lewy bodies13–15, Parkinson disease dementia15–18 and TAR DNA-binding protein 43 (TDP43) pathology in AD19–21 Associated with a reduction in cerebral glucose metabolism193,195–203 Associated with greater synaptic pathology in the brains of patients with AD66,160–163 Associated with increased risk of vascular cognitive impairment212,213 and pathologies that lead to neurovascular unit dysfunction214–217

AD, Alzheimer disease; APOE, apolipoprotein E.