Apolipoprotein E genotype is related to progression of white matter lesion load

Stroke. 2009 Oct;40(10):3186-90. doi: 10.1161/STROKEAHA.109.555839. Epub 2009 Jul 30.


Background and purpose: The relationship between white matter lesions (WMLs) and the apolipoprotein E genotype has been controversial from cross-sectional studies and no longitudinal finding has been reported. We investigated whether the apolipoprotein E genotype influences baseline and evolution over 4-year follow-up of WML volumes in a population-based sample of 1779 nondemented subjects aged 65 to 80 years old at enrollment.

Methods: The sample consisted of 3C-Dijon study participants who had 2 cerebral MRIs, at entry and at 4-year follow-up. WML volumes were estimated using a fully automatic procedure. We performed analysis of covariance to evaluate the relationship between apolipoprotein E genotype and WML load and progression.

Results: Multivariable analyses showed that epsilon4epsilon4 individuals had both significantly higher WML volume at baseline and higher WML increase over 4-year follow-up than noncarriers and heterozygous of the epsilon4 allele for apolipoprotein E genotype.

Conclusion: These findings suggest it might be important to take into account WML severity when assessing the relationship between apolipoprotein E and dementia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Apolipoprotein E4 / genetics
  • Apolipoproteins E / genetics*
  • Brain / metabolism
  • Brain / pathology*
  • Brain / physiopathology
  • Cohort Studies
  • DNA Mutational Analysis
  • Dementia / genetics*
  • Dementia / pathology*
  • Dementia / physiopathology
  • Disease Progression
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Genetic Testing
  • Genotype
  • Humans
  • Image Processing, Computer-Assisted
  • Magnetic Resonance Imaging
  • Male
  • Nerve Fibers, Myelinated / pathology*
  • Polymorphism, Genetic / genetics
  • Severity of Illness Index


  • Apolipoprotein E4
  • Apolipoproteins E