Apolipoprotein Eε4, other risk factors, and course of Alzheimer's disease

Background: The ε4 allele of apolipoprotein E (apoE ε4) is associated with late-onset Alzheimer's disease (AD), but its relationship to various aspects of AD has become increasingly unclear. We studied the relationship of apoE genotype in AD to educational attainment, history of heart disease or head injury, age of onset, gender, severity of illness, depression, psychotic symptoms, rate of dementia progression, and time from initial evaluation to nursing home placement. Methods: ApoE ε4 genotype was determined for 97 clinically diagnosed AD patients and 61 neuropathologically confirmed cases of AD. Results: Presence of one or more ε4 alleles occurred in 66% of AD cases as compared with 27% in control subjects (allele frequency was .40 for AD, .15 for control subjects). Among AD subjects there was no significant relationship between ε4 alleles and educational attainment, history of heart disease, head injury, age of onset, severity of illness, depression, history of depression, rate of dementia progression, or time to nursing home placement. Marginal correlations emerged between number of ε4 alleles, and delusions (p = .05) and hallucinations (p = .05). There was a trend toward increased ε4 homozygosity in patients with onset between ages 65 and 70 years. Conclusions: We did not find that individuals with one or two apoE ε4 alleles differed significantly in clinical course of AD from those without ε4 except for a trend toward increased psychotic symptoms in the group as a whole and an increase in ε4 homozygosity in patients with reported symptom onset in the late 60s.