Amyloid-beta (Abeta) 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 Abeta
peptides, we examined alterations in the clearance of
apoE-mediated Abeta
peptides after
sulfatide supplementation to cell culture systems. We demonstrated that
sulfatides markedly facilitate
apoE-mediated clearance of Abeta
peptides endogenously generated from H4-APPwt cells through an endocytotic pathway. Moreover, we found that the uptake of Abeta42 mediated by
sulfatides was selective in comparison to that of Abeta40. We excluded the possibility that the supplementation of
sulfatides and/or
apoE altered the production of Abeta
peptides from H4-APPwt cells through determination of the clearance of Abeta
peptides from conditioned H4-APPwt cell media by
neuroblastoma cells which do not appreciably generate Abeta
peptides. Finally, we demonstrated that the
sulfate galactose moiety of
sulfatides is essential for the
sulfatide-facilitated clearance of Abeta
peptides. Collectively, the current study provides insight into a molecular mechanism leading to Abeta 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.