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

Am J Psychiatry. 1998 Jun;155(6):779-84. doi: 10.1176/ajp.155.6.779.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • Apolipoprotein E4
  • Apolipoproteins E