Agrin binds to beta-amyloid (A beta), accelerates A beta fibril formation,and is localized to AB deposits in Alzheimer's disease brain

Agrin is an extracellular matrix heparan sulfate proteoglycan (HSPG) well k nown for its role in modulation of the neuromuscular junction duping develo pment. Although agrin is one of the major HSPGs of the brain, its function there remains elusive. Here we provide evidence suggesting a possible funct ion for agrin in Alzheimer's disease brain. Agrin protein binds the amyloid ogenic peptide A beta (1-40) in its fibrillar state via a mechanism that in volves the heparan sulfate glycosaminoglycan chains of agrin. Furthermore, agrin is able to accelerate A beta fibril formation and protect A beta (1-4 0) from proteolysis, in vitro. Supporting a biological significance for the se in vitro data, immunocytochemical studies demonstrate agrin's presence w ithin senile plaques and cerebrovascular amyloid deposits, and agrin immuno stained capillaries exhibit pathological alterations in AD brain. These dat a therefore suggest that agrin may be an important factor in the progressio n of AP peptide aggregation and/or its persistence in Alzheimer's disease b rain.