A cross-sectional study aimed at identifying how age and the APOE genotype are associated with emerging β-amyloid (Aβ) accumulation and cognitive dysfunction suggests that carrying an ε2 allele in the presence of an ε4 allele has a protective outcome, according to an article published in JAMA Neurology.
The analysis used screening data from the Anti-Amyloid Treatment in Asymptomatic Alzheimer Disease Study (A4 study). A total of 4,432 participants were included, having completed a fluorine 18-labelled (18F)-florbetapir positron emission tomography scan, with APOE genotype information, and a Clinical Dementia Rating of 0. The main outcomes were Aβ pathology and cognition.
APOE ε2 was associated with a reduction in both the overall and the age-dependent level of Aβ in the presence of ε4, with Aβ levels in the APOE ε2ε4 group increasing at less than half the rate with respect to increasing age, compared with the APOE ε3ε4 group.
These findings suggest that the protective outcome of carrying an ε2 allele in the presence of an ε4 allele against Aβ accumulation is important for potential treatments.
This strategy could represent an early treatment option, as many ε4 carriers begin to accumulate Aβ in early middle age, the authors conclude.