Apolipoprotein E mediates sulfatide depletion in animal models of Alzheimer's disease

Hua Cheng, Yunhua Zhou, David M. Holtzman, Xianlin Han

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Herein, we tested a recently proposed working model of apolipoprotein E (apoE)-mediated sulfatide metabolism/trafficking/homeostasis with two well-characterized amyloid precursor protein (APP) transgenic (Tg) animal models of Alzheimer's disease (AD) (i.e., APPV717F and APPsw) on a wild-type murine apoE background or after being bred onto an Apoe-/- background. As anticipated, lipidomics analysis demonstrated that the sulfatide levels in brain tissues were reduced beginning at approximately 6 months of age in APPV717F Tg, Apoe+/+ mice and at 9 months of age in APPsw Tg, Apoe+/+ mice relative to their respective non-APP Tg littermates. This reduction increased in both APP Tg mice as they aged. In contrast, sulfatide depletion did not occur in APP Tg, Apoe-/- animals relative to the Apoe-/- littermates. The lack of sulfatide depletion in APP Tg, Apoe-/- mice strongly supports the role of apoE in the deficient sulfatide content in APP Tg, Apoe+/+ mice. Collectively, through different animal models of AD, this study provides evidence for an identified biochemical mechanism that may be responsible for the sulfatide depletion at the earliest stages of AD.

Original languageEnglish (US)
Pages (from-to)1188-1196
Number of pages9
JournalNeurobiology of Aging
Volume31
Issue number7
DOIs
StatePublished - Jul 1 2010
Externally publishedYes

Keywords

  • APP transgenic mice
  • Alzheimer's disease
  • Apolipoprotein E
  • PDAPP
  • Shotgun lipidomics
  • Sphingolipidomics
  • Sulfatide
  • Tg2576

ASJC Scopus subject areas

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

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