BINDING OF VASCULAR HEPARAN-SULFATE PROTEOGLYCAN TO ALZHEIMERS AMYLOID PRECURSOR PROTEIN IS MEDIATED IN PART BY THE N-TERMINAL REGION OF A4PEPTIDE

The exact mechanisms of deposition and accumulation of amyloid in seni le plaques and in blood vessels in Alzheimer's disease remain unknown. Heparan sulfate proteoglycans may play an important role in amyloid d eposition in Alzheimer's disease. Previous investigations have demonst rated high affinity binding between heparan sulfate proteoglycans and the amyloid precursor, as well as with the A4 peptide. In the current studies, a specific vascular heparan sulfate proteoglycan found in sen ile plaques bound with high affinity to two amyloid protein precursors (APP695 and APP770). Vascular heparan sulfate proteoglycan also bound the Alzheimer's amyloid A4 peptide, and not other amyloid protein pre cusor regions studied, with high affinity. Both heparan sulfate glycos aminoglycan chains and chemically deglycosylated vascular heparan sulf ate proteoglycan protein core bound to A4. High affinity interactions between vascular heparan sulfate proteoglycan and the A4 peptide may p lay a role in the process of amyloidogenesis in Alzheimer's disease, b y localizing the site of deposition of A4, protecting A4 from further proteolysis, or by promoting aggregation and fibril formation.