ApoE4 disrupts sterol and sphingolipid metabolism in Alzheimer's but not normal brain

Veera Venkata Ratnam Bandaru, Juan Troncoso, David Wheeler, Olga Pletnikova, Jessica Wang, Kathy Conant, Norman J. Haughey

Research output: Contribution to journalArticlepeer-review

Abstract

The ε4 allele of ApoE is associated with an earlier onset and faster progression of Alzheimer's disease in patients with the familial form of this neurodegenerative condition. Although ApoE4 has been repeatedly associated with altered sphingomyelin and cholesterol levels in tissue culture and rodent models, there has not been a direct quantification of sphingomyelin or sterol levels in the brains of patients with different forms of ApoE. We measured the sphingolipid and sterol content of human brain tissues and found no evidence of perturbed sterol or sphingolipid biochemistry in the brains of individuals expressing ApoE4 who did not have a preexisting neurodegenerative condition. Nevertheless, ApoE4 was associated with gross abnormalities in the sterol and sphingolipid content of numerous brain regions in patients with Alzheimer's diseaase. The findings suggest that ApoE4 may not by itself alter sterol or sphingolipid metabolism in the brain under normal conditions, but that other neuropathologic changes of Alzheimer's are required to unmask the effect of ApoE4, and to perturb sterol and sphingolipid biochemistry.

Original languageEnglish (US)
Pages (from-to)591-599
Number of pages9
JournalNeurobiology of aging
Volume30
Issue number4
DOIs
StatePublished - Apr 2009

Keywords

  • Alzheimer's disease
  • ApoE
  • ApoE4
  • Apolipoprotein
  • Ceramide
  • Cholesterol
  • Sphingolipid
  • Sphingomeylin
  • Sterol

ASJC Scopus subject areas

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

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