Glypican-1 as an Aβ binding HSPG in the human brain: its localization in DIG domains and possible roles in the pathogenesis of Alzheimer’s disease

SPECIFIC AIMSThe amyloid deposition whose major component is the 39-43 amino acid peptide, termed β-amyloid protein (Aβ), is considered to be important in Alzheimer’s disease (AD) pathology, but the precise mechanism of its accumulation in AD brain is unclear. Although there are studies of the association between Aβ and heparan sulfate proteoglycans (HSPGs), they demonstrated colocalization in plaques or binding ability of HSPGs derived from tissues other than human brain. It is not fully understood whether HSPGs are involved in neuronal cell death in AD brain. Our aims are to identify Aβ binding HSPG(s) from human brain and to investigate their roles in Aβ accumulation and neuronal cell death.PRINCIPAL FINDINGS1. Identification of glypican-1 as an Aβ binding HSPG from human brainTo identify HSPGs derived from the human brain with the capacity to bind Aβ, control human brain lysates were separated using anion exchange DEAE-Sepharose chromatography and fractions containing possible Aβ binding protein(s) we...