Major decrease in the volume of the entorhinal cortex in patients with Alzheimer's disease carrying the apolipoprotein E ε4 allele

Abstract

Objective - Recent evidence indicates that the apolipoprotein E (ApoE) ε4 allele is a risk factor for developing Alzheimer's disease. It has also been proposed that it is associated with increased counts of amyloid plaques and neurofibrillary tangles that in turn are neuropathological hallmarks initially appearing in the medial temporal lobe structures in Alzheimer's disease. In this study, the effect of the ApoE ε4 allele on the volume of the entorhinal cortex was evaluated in vivo. Methods - The volume of the entorhinal cortex was measured on MR images using a recently designed histology based protocol in 16 patients with Alzheimer's disease with ApoE ε4 (mean age 70.4 (SD 9.9)), 11 patients with Alzheimer's disease without ApoE ε4 (mean age 69.1 (SD 7.1)), and in 31 healthy age and sex matched normal controls (72.2 (SD 3.9)). The patients met the NINCDS-ADRDA criteria for probable Alzheimer's disease and were in mild to moderate stages of the disease. MRI was performed with a 1.5 Tesla Magnetom and a 3D technique permitting the reconstruction of 2.0 mm thick contiguous slices perpendicular to the axis of the anterior-posterior commissure. Results - The patients with Alzheimer's disease without the ApoE ε4 allele had atrophy in the entorhinal cortex, the volume was reduced by 27% compared with control subjects. However, the most prominent shrinkage (45%) was seen in patients with Alzheimer's disease with the ApoE ε4 allele (p = 0.0001). The effect of ε4 on the entorhinal cortex volume was especially prominent in female patients with Alzheimer's disease compared to male patients with Alzheimer's disease (p = 0.014). Additionally, patients with the ApoE ε4 allele had inferior performance in verbal and visual memory functions than those without the allele Conclusions - Volumetric MRI measurements disclose that ApoE ε4 is associated with the degree of atrophy in the entorhinal cortex in early Alzheimer's disease, this effect being especially prominent in female patients with Alzheimer's disease.