Heparan Sulfate Proteoglycan Is Associated with Amyloid Plaques and Neuroanatomically Targeted PrP Pathology throughout the Incubation Period of Scrapie-Infected Mice |
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Authors: | PA McBride MI Wilson P Eikelenboom A Tunstall ME Bruce |
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Institution: | aBBSRC and MRC Neuropathogenesis Unit, Institute for Animal Health, Ogston Building, West Mains Road, Edinburgh, EH9 3JF, Scotland, United Kingdom;bDepartment of Psychiatry, Vrije Universiteit, Valeriuskliniek, Valeriusplein 9, 1075 BG, Amsterdam, The Netherlands;cDepartment of Biological Sciences, Napier University, 219 Colinton Road, Edinburgh, EH14 1DJ, Scotland, United Kingdom |
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Abstract: | Heparan sulfate proteoglycan (HSPG) has been found to be associated with amyloid deposits in a number of diseases including the cerebral amyloid plaques of Alzheimer's disease and the transmissible spongiform encephalopathies (TSEs). The role of HSPG in amyloid formation and the neurodegenerative pathology of these diseases have not been established. We have addressed these questions using a scrapie mouse model which exhibits both amyloid and nonamyloid deposition of abnormal PrP protein, the protein marker of TSE infection. The distribution of HSPG was examined throughout the course of the disease in the brains of experimentally 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 neuroanatomically targeted forms. Scrapie-associated HSPG was present from 70 days after infection, the earliest time-point examined, in the same target areas as abnormal PrP. The association with amyloid plaques may indicate that HSPG is involved in amyloid plaque formation and/or persistence but involvement with early diffuse forms of PrP suggests a more fundamental role in scrapie pathogenesis. |
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Keywords: | amyloid plaques PrP HSPG immunocytochemistry scrapie |
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