HEPARAN-SULFATE PROTEOGLYCAN IS ASSOCIATED WITH AMYLOID PLAQUES AND NEUROANATOMICALLY TARGETED PRP PATHOLOGY THROUGHOUT THE INCUBATION PERIOD OF SCRAPIE-INFECTED MICE

Heparan sulfate proteoglycan (HSPG) has been found to be associated wi th amyloid deposits in a number of diseases including the cerebral amy loid plaques of Alzheimer's disease and the transmissible spongiform e ncephalopathies (TSEs). The role of HSPG: in amyloid formation and the neurodegenerative pathology of these diseases have not been establish ed. We have addressed these questions using a scrapie mouse model whic h exhibits both amyloid and nonamyloid deposition of abnormal PrP prot ein, the protein marker of TSE infection. The distribution of HSPG was examined throughout the course of the disease in the brains of experi mentally infected mice and compared with the distribution of abnormal PrP. Abnormally high levels of HSPG were associated with most types of PrP pathology including all plaque types and diffuse neuroanatomicall y targeted forms. Scrapie-associated HSPG was present from 70 days aft er infection, the earliest time-point examined, in the same target are as as abnormal PrP. The association with amyloid plaques may indicate that HSPG is involved in amyloid plaque formation and/or persistence b ut involvement with early diffuse forms of PrP suggests a more fundame ntal role in scrapie pathogenesis. (C) 1998 Academic Press.