Microglia and the pathogenesis of spongiform encephalopathies

Alterations in the phenotype and function of microglia, the resident mononuclear phagocytes of the central nervous system, are among the earliest indications of pathology within the brain and spinal cord. The prion diseases, also known as spongiform encephalopathies, are fatal neurodegenerative disorders with sporadic, genetic or acquired infectious manifestations. A hallmark of all prion diseases is the aberrant metabolism and resulting accumulation of the prion protein. Conversion of the normal cellular protein [PrP(c)] into the abnormal pathogenic (or disease-causing) isoform [PrP(Sc)] involves a conformational alteration whereby the alpha-helical content is transformed into beta-sheet. The histological characteristics of these disorders are spongiform change, astrocytosis, neuronal loss and progressive accumulation of the protease-resistant prion isoform. An additional upregulation in microglial response has been reported in Kuru, Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Scheinker syndrome (GSS), scrapie, in transgenic murine models and in culture, where microglial activation often accompanies prion protein deposition and neuronal loss. This article will review the roles of microglia in spongiform encephalopathies

A quantitative analysis of cellular prion protein (PrPc) expression in Alzheimer's disease, diffuse Lewy body disease and in normal brain [poster presentation]

Introduction: Cellular prion protein (PrPc) is a normal glycosyl phosphatidylinositol-anchored protein expressed on a wide variety of cell types. Within the CNS, low levels of PrPc are particularly associated with neurons in normal healthy individuals. In contrast, a more pronounced expression of this protein may occur in certain neurodegenerative disorders (Esiri et al. Neuropath Appl Neurobiol 2000; 26: 273; Voigtlander et al. Acta Neuropathol 2001; 101: 417). Overexpression of PrPc has itself been reported to demonstrate neuropathology in transgenic mice (Westaway et al. Cell 1994; 76: 117). The present study investigated whether prion protein is up-regulated in two well-characterized neurodegenerative disorders: Alzheimer's disease (AD) and diffuse Lewy body disease (DLBD)

Regional expression of synaptic markers in Creutzfeldt-Jakob disease (platform presentation)

Cellular prion protein (PrPe) is a membrane-bound glycoprotein, reportedly expressed at high levels at synapses. The function of PrPe is uncertain. However, the formation of an abnormal isoform (PrPSe) is considered central to the pathogenesis of Creutzfeldt-Jakob disease (CJD), and synaptic damage has been suggested as an early pathological event in CJD