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Apolipoprotein E epsilon 4 allele and whole brain atrophy in late-onset Alzheimer's disease.

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. METHOD: 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.

Pubmed ID: 9619150


  • Yasuda M
  • Mori E
  • Kitagaki H
  • Yamashita H
  • Hirono N
  • Shimada K
  • Maeda K
  • Tanaka C


The American journal of psychiatry

Publication Data

June 18, 1998

Associated Grants


Mesh Terms

  • Aged
  • Alleles
  • Alzheimer Disease
  • Analysis of Variance
  • Anatomy, Cross-Sectional
  • Apolipoprotein E4
  • Apolipoproteins E
  • Atrophy
  • Brain
  • Educational Status
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Neuropsychological Tests
  • Severity of Illness Index
  • Sex Factors