This pilot project proposes to study human brain synaptosomal heparan sulfate proteoglycan (HSPG) and its possible role in the pathogenesis of senile dementia of the Alzheimer's type (SDAT). HSPG plays an important role in normal neuronal function, and alterations in neuronal HSPG may occur with aging and be involved in the pathogenesis of SDAT. Of interest, recent data suggest that the amyloid found in SDAT is identical to a species of HSPG derived from a rat neuronal cell line. To our knowledge neuronal HSPG has not been isolated from human brain. The ADRC provides a unique opportunity to conduct studies on human brain synaptosomal HSPG from both normal individuals and patients with SDAT. We will attempt to demonstrate the presence of alterations in human brain synaptosomal HSPG in SDAT and the immunochemical and biochemical relationship between that HSPG and beta-amyloid. The proposed studies should contribute to our understanding of the nature of human brain synaptosomal HSPG in normal aging and SDAT.