title: Dissecting the gene dose-effects of the APOE ε4 and ε2 alleles on hippocampal volumes in aging and Alzheimer's disease.
abstract: OBJECTIVE
  To investigate whether there is a specific dose-dependent effect of the Apolipoprotein E (APOE) ε4 and ε2 alleles on hippocampal volume, across the cognitive spectrum, from normal aging to Alzheimer's Disease (AD).
  
  
  METHODS
  We analyzed MR and genetic data on 662 patients from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database-198 cognitively normal controls (CN), 321 mild-cognitive impairment (MCI) subjects, and 143 AD subjects-looking for dose-dependent effects of the ε4 and ε2 alleles on hippocampal volumes. Volumes were measured using a fully-automated algorithm applied to high resolution T1-weighted MR images. Statistical analysis consisted of a multivariate regression with repeated-measures model.
  
  
  RESULTS
  There was a dose-dependent effect of the ε4 allele on hippocampal volume in AD (p = 0.04) and MCI (p = 0.02)-in both cases, each allele accounted for loss of >150 mm(3) (approximately 4%) of hippocampal volume below the mean volume for AD and MCI subjects with no such alleles (Cohen's d = -0.16 and -0.19 for AD and MCI, respectively). There was also a dose-dependent, main effect of the ε2 allele (p<0.0001), suggestive of a moderate protective effect on hippocampal volume-an approximately 20% per allele volume increase as compared to CN with no ε2 alleles (Cohen's d = 0.23).
  
  
  CONCLUSIONS
  Though no effect of ε4 was seen in CN subjects, our findings confirm and extend prior data on the opposing effects of the APOE ε4 and ε2 alleles on hippocampal morphology across the spectrum of cognitive aging.
authors: Department of Radiology, Duke University School of Medicine, Durham, NC, USA.
authors: Christopher A
authors: CA
authors: Hostage
authors: Kingshuk
authors: K
authors: Roy Choudhury
authors: Pudugramam Murali
authors: PM
authors: Doraiswamy
authors: Jeffrey R
authors: JR
authors: Petrella
mesh_terms: D000367:Age Factors; D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology*; D053329:Apolipoprotein E2 / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics*; D060825:Cognitive Dysfunction / Q000235:genetics; D005260:Female; D018628:Gene Dosage; D005787:Gene Frequency; D005838:Genotype; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D008297:Male
chemical_list: D053329:Apolipoprotein E2; D053327:Apolipoprotein E4
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