title: Apolipoprotein E epsilon 4 allele and whole brain atrophy in late-onset Alzheimer's disease.
abstract: OBJECTIVE
  Diffuse brain atrophy is one of the gross pathological features of Alzheimer's disease and is a result of degenerative changes. The epsilon 4 allele of apolipoprotein E (APOE) is a risk factor or susceptibility gene in late-onset sporadic Alzheimer's disease and may influence the pathological changes associated with the disease. The aim of this study was to examine the relationship between the APOE epsilon 4 allele and whole brain atrophy.
  
  
  METHODS
  Whole brain volume was quantified by using high-resolution magnetic resonance imaging and the computerized brain segmentation technique in 178 patients with late-onset sporadic Alzheimer's disease who carried no APOE epsilon 4 alleles (N = 62), one epsilon 4 allele (N = 93), or two (N = 23) and had comparable clinical severity of dementia.
  
  
  RESULTS
  An apparent positive correlation was found between normalized whole brain volume (relative to total intracranial volume) and number of APOE epsilon 4 alleles; i.e., patients carrying two APOE epsilon 4 alleles had the least brain atrophy. This association between the APOE epsilon 4 allele and brain volume was similar in women and men and was independent of age, level of education, duration of illness since symptom onset, and severity of dementia.
  
  
  CONCLUSIONS
  The results indicate that cognitive dysfunction progresses before severe brain atrophy develops in patients carrying the APOE epsilon 4 allele and suggest that an APOE epsilon 4-allele-related mechanism that affects neuronal function before a decrement in brain matter is involved in the development of dementia.
authors.affiliation: Division of Neurosciences, Hyogo Institute for Aging Brain and Cognitive Disorders, Japan. yasuda@hiabcd.go.jp
authors.forename: M
authors.initials: M
authors.lastname: Yasuda
authors.forename: E
authors.initials: E
authors.lastname: Mori
authors.forename: H
authors.initials: H
authors.lastname: Kitagaki
authors.forename: H
authors.initials: H
authors.lastname: Yamashita
authors.forename: N
authors.initials: N
authors.lastname: Hirono
authors.forename: K
authors.initials: K
authors.lastname: Shimada
authors.forename: K
authors.initials: K
authors.lastname: Maeda
authors.forename: C
authors.initials: C
authors.lastname: Tanaka
mesh_terms: D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D000704:Analysis of Variance; D019412:Anatomy, Cross-Sectional; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D001284:Atrophy; D001921:Brain / Q000033:anatomy & histology* / Q000473:pathology; D004522:Educational Status; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D012720:Severity of Illness Index; D012737:Sex Factors
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E