APOE ε4 is associated with disproportionate progressive hippocampal atrophy in AD

Alzheimer's Disease Neuroimaging Initiative

Research output: Contribution to journalArticlepeer-review

48 Citations (SciVal)


OBJECTIVES: To investigate whether APOE ε4 carriers have higher hippocampal atrophy rates than non-carriers in Alzheimer's disease (AD), mild cognitive impairment (MCI) and controls, and if so, whether higher hippocampal atrophy rates are still observed after adjusting for concurrent whole-brain atrophy rates.

METHODS: MRI scans from all available visits in ADNI (148 AD, 307 MCI, 167 controls) were used. MCI subjects were divided into "progressors" (MCI-P) if diagnosed with AD within 36 months or "stable" (MCI-S) if a diagnosis of MCI was maintained. A joint multi-level mixed-effect linear regression model was used to analyse the effect of ε4 carrier-status on hippocampal and whole-brain atrophy rates, adjusting for age, gender, MMSE and brain-to-intracranial volume ratio. The difference in hippocampal rates between ε4 carriers and non-carriers after adjustment for concurrent whole-brain atrophy rate was then calculated.

RESULTS: Mean adjusted hippocampal atrophy rates in ε4 carriers were significantly higher in AD, MCI-P and MCI-S (p≤0.011, all tests) compared with ε4 non-carriers. After adjustment for whole-brain atrophy rate, the difference in mean adjusted hippocampal atrophy rate between ε4 carriers and non-carriers was reduced but remained statistically significant in AD and MCI-P.

CONCLUSIONS: These results suggest that the APOE ε4 allele drives atrophy to the medial-temporal lobe region in AD.

Original languageEnglish
Pages (from-to)e97608
JournalPLoS ONE
Issue number5
Publication statusPublished - 30 May 2014


  • Aged
  • Alleles
  • Alzheimer Disease/genetics
  • Apolipoprotein E4/genetics
  • Atrophy/genetics
  • Case-Control Studies
  • Cognitive Dysfunction/genetics
  • Cross-Sectional Studies
  • Female
  • Hippocampus/pathology
  • Humans
  • Longitudinal Studies
  • Male


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