Mapping the effect of APOE ε4 on gray matter loss in Alzheimer's disease in vivo

M. Pievani, P. E. Rasser, S. Galluzzi, L. Benussi, R. Ghidoni, F. Sabattoli, M. Bonetti, G. Binetti, P. M. Thompson, G. B. Frisoni

Research output: Contribution to journalArticlepeer-review

Abstract

Previous studies suggest that in Alzheimer's disease (AD) the Apolipoprotein E (APOE) ε4 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 identify APOE-related patterns of cortical atrophy in AD using an advanced computational anatomy technique. We studied 15 AD patients carriers (ε4+, age: 72 ± 10 SD years, MMSE: 20 ± 3 SD) and 14 non-carriers (ε4-, age: 69 ± 9, MMSE: 20 ± 5) of the ε4 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. ε4+ and ε4- patients showed similar performance on neuropsychological tests (p > .05, t-test). Diffuse cortical atrophy was detected for both ε4+ (p = .0001, permutation test) and ε4- 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). APOE effect in AD was not significant (p > .74, ANOVA), but a significant APOE by region (temporal vs fronto-parietal cortex) interaction was detected (p = .002, ANOVA), in both early and late-onset patients (p <.05, ANOVA). We conclude that the ε4 allele modulates disease phenotype in AD, being associated with a pattern of differential temporal and fronto-parietal vulnerability.

Original languageEnglish
Pages (from-to)1090-1098
Number of pages9
JournalNeuroImage
Volume45
Issue number4
DOIs
Publication statusPublished - May 1 2009

Keywords

  • Alzheimer's disease
  • Apolipoprotein E
  • Computational neuroanatomy
  • Cortical atrophy
  • MRI

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Neurology

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