APOE-ε4 is associated with less frontal and more medial temporal lobe atrophy in AD

Objective: To test the hypothesis that the ε4 allele of APOE is associated with a region-specific pattern of brain atrophy in AD. Methods: Volumes of the hippocampi, entorhinal cortices, and anterior temporal and frontal lobes were measured in 28 mild to moderate AD patients and 30 controls using MRI. Within the AD group, 14 patients were noncarriers (-/-), 9 were heterozygous (ε4/-), and 5 were homozygous (ε4/4) for the ε4 allele. Dementia severity was similar across the three AD groups. Results: Smaller volumes were found with increasing dose of the ε4 allele in the hippocampus, entorhinal cortex, and anterior temporal lobes in AD patients. When compared with controls, the volume loss in the right and left temporal regions ranged from -15.3 to -22.7% in the -/- AD group, from -26.2 to -36.0% in the ε4/- group, and from -24.0 to -48.0% in the ε4/4 group (p < 0.0005). In contrast, larger volumes were found in the frontal lobes with increasing ε4 gene dose. When compared with controls, volume differences of the right frontal lobe were -11.8% in the -/- AD group, -8.5 in the ε4/- group, and - 1.4% in the ε4/4 group (p = 0.03). Conclusions: We found smaller volumes in the temporal lobe regions but larger volumes in the frontal lobes with increasing APOE-ε4 gene dose in AD patients. These data suggest a region- specific biological effect of the ε4 allele in the brains of AD patients.