Mapping the effect of APOE [epsilon]4 on gray matter loss in Alzheimer's disease in vivo

• Published in: NeuroImage (Orlando, Fla.) Vol. 45; no. 4; p. 1090
• Main Authors: Pievan i, M, Rasser, PE, Galluzzi, S, Benussi, L, Ghidoni, R, Sabattoli, F, Bonetti, M, Binetti, G, Thompson, PM, Frisoni, GB
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Limited 01.05.2009
• Subjects: Age; Alzheimer's disease; Memory; Standard deviation; Studies
• ISSN: 1053-8119; 1095-9572
• DOI: 10.1016/j.neuroimage.2009.01.009

Previous studies suggest that in Alzheimer's disease (AD) the Apolipoprotein E (APOE) [straight epsilon]4 allele is associated with greater vulnerability of medial temporal lobe structures. However, less is known about its effect on the whole cortical mantle. Here we aimed to identifyAPOE-related patterns of cortical atrophy in AD using an advanced computational anatomy technique. We studied 15 AD patients carriers ([straight epsilon]4+, age: 72±10 SD years, MMSE: 20±3 SD) and 14 non-carriers ([straight epsilon]4-, age: 69±9, MMSE: 20±5) of the [straight epsilon]4 allele and compared them to 29 age-and-sex matched controls (age: 70±9, MMSE: 28±1). Each subject underwent a clinical evaluation, a neuropsychological battery, and high-resolution MRI. UCLA's cortical pattern matching technique was used to identify regions of local cortical atrophy. [straight epsilon]4+ and [straight epsilon]4- patients showed similar performance on neuropsychological tests (p>.05,t-test). Diffuse cortical atrophy was detected for both [straight epsilon]4+ (p=.0001,permutation test) and [straight epsilon]4- patients (p=.0001,permutation test) relative to controls, and overall gray matter loss was about 15% in each patients group. Differences in gray matter loss between carriers and non-carriers mapped to the temporal cortex and right occipital pole (20% greater loss in carriers) and to the posterior cingulate, left orbitofrontal and dorsal fronto-parietal cortex (5-15% greater loss in non-carriers).APOEeffect in AD was not significant (p>.74, ANOVA), but a significantAPOEby region (temporalvsfronto-parietal cortex) interaction was detected (p=.002, ANOVA), in both early and late-onset patients (p<.05, ANOVA). We conclude that the [straight epsilon]4 allele modulates disease phenotype in AD, being associated with a pattern of differential temporal and fronto-parietal vulnerability.