Apolipoprotein E genotype and noncognitive symptoms in Alzheimer's disease

Biol Psychiatry. 1999 Feb 15;45(4):422-5. doi: 10.1016/s0006-3223(98)00041-9.


Background: The apolipoprotein E (ApoE) epsilon 4 allele confers significant risk for Alzheimer's disease and is associated with a greater amyloid burden in the brain. Future treatments may target molecular mechanisms associated with this allele, and it is important to define any phenotypic characteristics that correspond to this genotype. We sought to clarify the relationship between ApoE status and noncognitive symptoms in Alzheimer's disease patients.

Methods: Possible and probable Alzheimer's disease patients from a clinical trial (n = 605) were assessed with the 10-item Neuropsychiatric Inventory cross-sectionally prior to treatment, and their ApoE genotype was determined. Among the population studied, the following numbers with specific genotypes were studied: 23-2/3, 17-2/4, 209-3/3, 288-3/4, 68-4/4.

Results: When correlations were controlled for the patient's level of cognitive impairment, there was no relationship between epsilon 4 dose and any of the 10 noncognitive symptoms assessed, including psychosis, mood changes, and personality alterations.

Conclusions: Among patients with comparable disease severity, the epsilon 4 allele does not confer additional psychiatric morbidity.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / classification
  • Alzheimer Disease / genetics*
  • Apolipoprotein E4
  • Apolipoproteins E / genetics*
  • Behavioral Symptoms / classification
  • Behavioral Symptoms / genetics*
  • Chi-Square Distribution
  • Cross-Sectional Studies
  • Depression / genetics
  • Female
  • Gene Dosage
  • Genotype
  • Humans
  • Male
  • Mental Status Schedule
  • Middle Aged
  • Phenotype
  • Psychomotor Agitation / genetics
  • Severity of Illness Index


  • Apolipoprotein E4
  • Apolipoproteins E