Smaller hippocampal volume in APOE ε4 carriers independent of amyloid-β (Aβ) burden

To investigate the association of the APOE ε4 genotype with hippocampal volume, independent of Aβ burden.

This cross-sectional study included 71 participants with mild cognitive impairment or mild AD. All participants were divided into carriers or non-carriers of the ε4 allele. The main outcome was hippocampal volume measured using structural magnetic resonance imaging; ¹⁸F-florbetaben positron emission tomography was additionally performed to investigate the association of APOE ε4 genotype with hippocampal volumes, independently of Aβ burden. Analysis of covariance was conducted to compare the differences in hippocampal volumes between carriers and non-carriers of the ε4 allele after controlling for global Aβ burden or local hippocampal Aβ burden.

The APOE ε4 genotype was associated with a smaller right and total hippocampal volume (right: 3160.16 ± 365.71 vs. 3365.24 ± 434.88, p < 0.05; total: 6257.48 ± 790.60 vs. 6599.52 ± 840.58, p < 0.05), independent of Aβ burden.

Our findings on the association of APOEε4 genotype with hippocampal volume independent of Aβ burden suggest that the APOEε4 genotype may contribute to hippocampal neurodegeneration through an Aβ-independent mechanism.