Serum cholesterol and variant in cholesterol-related gene CETP predict white matter microstructure

Alzheimer’s Disease Neuroimaging Initiative (ADNI)

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


Several common genetic variants influence cholesterol levels, which play a key role in overall health. Myelin synthesis and maintenance are highly sensitive to cholesterol concentrations, and abnormal cholesterol levels increase the risk for various brain diseases, including Alzheimer's disease. We report significant associations between higher serum cholesterol (CHOL) and high-density lipoprotein levels and higher fractional anisotropy in 403 young adults (23.8 ± 2.4years) scanned with diffusion imaging and anatomic magnetic resonance imaging at 4Tesla. By fitting a multi-locus genetic model within white matter areas associated with CHOL, we found that a set of 18 cholesterol-related, single-nucleotide polymorphisms implicated in Alzheimer's disease risk predicted fractional anisotropy. We focused on the single-nucleotide polymorphism with the largest individual effects, CETP (rs5882), and found that increased G-allele dosage was associated with higher fractional anisotropy and lower radial and mean diffusivities in voxel-wise analyses of the whole brain. A follow-up analysis detected white matter associations with rs5882 in the opposite direction in 78 older individuals (74.3 ± 7.3years). Cholesterol levels may influence white matter integrity, and cholesterol-related genes may exert age-dependent effects on the brain.

Original languageEnglish (US)
Pages (from-to)2504-2513
Number of pages10
JournalNeurobiology of aging
Issue number11
StatePublished - Nov 1 2014


  • Aging
  • Brain structure
  • Cholesterol
  • DTI
  • Development
  • Imaging genetics

ASJC Scopus subject areas

  • Clinical Neurology
  • Geriatrics and Gerontology
  • Aging
  • Neuroscience(all)
  • Developmental Biology


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