Sulfatides facilitate apolipoprotein E-mediated amyloid-β peptide clearance through an endocytotic pathway

Youchun Zeng, Xianlin Han

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Amyloid-β (Aβ) accumulation and fibril formation are key pathologic characteristics of Alzheimer's disease (AD). We have previously found that sulfatide depletion occurs at the earliest stages of AD. To further identify the role of sulfatides in the pathogenesis of AD as well as the interactions between apolipoprotein E (apoE), sulfatides, and Aβ peptides, we examined alterations in the clearance of apoE-mediated Aβ peptides after sulfatide supplementation to cell culture systems. We demonstrated that sulfatides markedly facilitate apoE-mediated clearance of Aβ peptides endogenously generated from H4-APPwt cells through an endocytotic pathway. Moreover, we found that the uptake of Aβ42 mediated by sulfatides was selective in comparison to that of Aβ40. We excluded the possibility that the supplementation of sulfatides and/or apoE altered the production of Aβ peptides from H4-APPwt cells through determination of the clearance of Aβ peptides from conditioned H4-APPwt cell media by neuroblastoma cells which do not appreciably generate Aβ peptides. Finally, we demonstrated that the sulfate galactose moiety of sulfatides is essential for the sulfatide- facilitated clearance of Aβ peptides. Collectively, the current study provides insight into a molecular mechanism leading to Aβ clearance/deposition, highlights the significance of sulfatide deficiency at the earliest clinically recognizable stage of AD, and identifies a potential new direction for therapeutic intervention for the disease.

Original languageEnglish (US)
Pages (from-to)1275-1286
Number of pages12
JournalJournal of neurochemistry
Volume106
Issue number3
DOIs
StatePublished - Aug 2008
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Amyloid-β clearance
  • Apolipoprotein E
  • Endocytosis
  • Sulfatide

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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