Markers of cholesterol transport are associated with amyloid deposition in the brain

Neurobiol Aging. 2014 Apr;35(4):802-7. doi: 10.1016/j.neurobiolaging.2013.09.040. Epub 2013 Oct 3.

Abstract

Cholesterol is implicated in the development of late-onset Alzheimer's disease (AD). We sought to determine the associations between beta amyloid (Aβ) plaque deposition in vivo using Pittsburgh compound B (PiB) and several indices of cholesterol homeostasis (i.e., total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, apolipoprotein E (ApoE), clusterin, oxysterol metabolites of cholesterol, and previously reported genes associated with late-onset AD) in 175 nondemented elderly subjects. High Aβ deposition was associated significantly with a lower Mini-Mental State Examination score (<27 points, p = 0.04), high systolic blood pressure (p = 0.04), carrying the apolipoprotein E epsilon 4 allele (p < 0.01), and lower plasma ApoE levels (p = 0.02), and variation in the ABCA7 (p = 0.02) and EPHA1 genes (p = 0.02). Cholesterol measures were not related to Aβ deposition in this cohort of nondemented elderly adults. However, plasma and genetic factors relating to cholesterol transport were associated with Aβ deposition in the brain. A better understanding of cholesterol transport mechanisms may lead to the design of potential targets for the prevention of Aβ deposition in the brain.

Keywords: Alzheimer's disease; Cholesterol; Genes; Imaging; Lipids; Mild cognitive impairment; Oldest old.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • ATP-Binding Cassette Transporters
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / prevention & control
  • Amyloid beta-Peptides / metabolism*
  • Apolipoprotein E4
  • Biological Transport / genetics*
  • Brain / metabolism*
  • Brain / pathology*
  • Cholesterol / metabolism*
  • Cohort Studies
  • Female
  • Homeostasis
  • Humans
  • Male
  • Molecular Targeted Therapy
  • Plaque, Amyloid / genetics*
  • Plaque, Amyloid / prevention & control
  • Receptor, EphA1

Substances

  • ABCA7 protein, human
  • ATP-Binding Cassette Transporters
  • Amyloid beta-Peptides
  • Apolipoprotein E4
  • Cholesterol
  • Receptor, EphA1