Morphogenesis of amyloid plaques in 87V murine scrapie.
Amyloid plaques of scrapie-infected mouse brains are composed of fibrillar forms of a host coded, cell surface sialoglycoprotein called PrP (prion protein). Serial ultrastructural immunogold staining was performed on plaques identified by light microscopic immunocytochemistry of brains of VM mice infected with the 87V strain of scrapie. Classical plaques, 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 processes and in the associated extracellular spaces. Frequent microglial cells and occasional astrocytes contained PrP within lysosomes. Other plaques with few or no recognizable amyloid fibrils were frequent and were termed primitive plaques. PrP could be demonstrated in a non-fibrillar form at the plasmalemma and in the extracellular spaces between neurites of such plaques. Many primitive plaques showed little or no sub-cellular pathology associated with the PrP accumulation. PrP was closely associated with the plasmalemma of occasional dendrites passing towards the centre of primitive plaques. These results suggest that plaques are formed around one or more PrP releasing dendrites. PrP accumulates in the extracellular spaces adjacent to such processes prior to its spontaneous aggregation into fibrils. Lysosomal accumulation of PrP in microglia and astrocytes located at the periphery of plaques suggest that these cells are involved in the phagocytosis of excess or abnormal PrP.
Jeffrey
M
M
Central Veterinary Laboratory, Lasswade Veterinary Laboratory, Penicuik, UK.
Goodsir
C M
CM
Bruce
M E
ME
McBride
P A
PA
Farquhar
C
C
D000682:Amyloid / Q000648:ultrastructure*; D000818:Animals; D001921:Brain / Q000473:pathology*; D002540:Cerebral Cortex / Q000648:ultrastructure*; D007120:Immunochemistry; D051379:Mice; D008854:Microscopy, Electron; D009457:Neuroglia / Q000648:ultrastructure; D012608:Scrapie / Q000473:pathology*; D012795:Sialoglycoproteins / Q000648:ultrastructure
D000682:Amyloid; D012795:Sialoglycoproteins