MORPHOGENESIS OF AMYLOID PLAQUES IN 87V MURINE SCRAPIE

Amyloid plaques of scrapie-infected mouse brains are composed of fibri llar forms of a host coded, cell surface sialoglycoprotein called PrP (prion protein). Serial ultrastructural immunogold staining was perfor med on plaques identified by light microscopic immunocytochemistry of brains of VM mice infected with the 87V strain of scrapie. Classical p laques, of a kuru-type morphology, were composed of a central core of bundles of amyloid fibrils. Amyloid fibrils of classical plaques were immunoreactive for PrP. In addition, PrP was also found at the plaque periphery, in the absence of fibrils, at the plasmalemma of cell proce sses and in the associated extracellular spaces. Frequent microglial c ells and occasional astrocytes contained PrP within lysosomes. Other p laques with few or no recognizable amyloid fibrils were frequent and w ere termed primitive plaques. PrP could be demonstrated in a non-fibri llar form at the plasmalemma and in the extracellular spaces between n eurites of such plaques. Many primitive plaques showed little or no su b-cellular pathology associated with the PrP accumulation. PrP was clo sely associated with the plasmalemma of occasional dendrites passing t owards the centre of primitive plaques. These results suggest that pla ques are formed around one or more PrP releasing dendrites. PrP accumu lates in the extracellular spaces adjacent to such processes prior to its spontaneous aggregation into fibrils. Lysosomal accumulation of Pr P in microglia and astrocytes located at the periphery of plaques sugg est that these cells are involved in the phagocytosis of excess or abn ormal PrP.