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Neuropathology of unconventional virus infections: molecular pathology of spongiform change and amyloid plaque deposition.
- Source :
-
Ciba Foundation symposium [Ciba Found Symp] 1988; Vol. 135, pp. 24-36. - Publication Year :
- 1988
-
Abstract
- To the triad of neuronal loss, gliosis and spongiform change as characteristic morphological changes associated with infection of the central nervous system, one can now add the presence of scrapie-associated filaments (SAF)/PrP rods. While the host's immune response is conspicuous by its absence, the vigorous astrocytic response is presumptive evidence of the host's ability to recognize and respond to the primary neuronal insult. We assume that the spongiform change and vacuolation of neurons are of fundamental importance in the pathogenesis of the disease, realizing that neither is specific or essential for the replication of the infectious agent. The topographical distribution of lesions is partly explained by the portal of entry and retrograde spread of the virus. The temporal progression of the lesions is more clearly determined by the host genes, best illustrated by studies of the incubation period. The molecular basis of the spongiform change is unknown but it is presumed to involve some disturbance of membrane metabolism. The recognition of PrP as a membrane glycoprotein invites proposals for its role in the development of these spongiform lesions. Extracellular amyloid occurs as plaques or congophilic angiopathy in some instances, and provides the best evidence that Alzheimer's disease (AD) is in some way related to the unconventional virus diseases. However, the protein subunit (A4) of the amyloid fibril in AD and its precursor are quite distinct from the PrP subunit which constitutes the amyloid fibril in these infectious diseases. It is still unclear whether the PrP subunit in the SAF has exactly the same composition as in the extracellular amyloid fibril. Our results suggest that only a fragment of the PrP molecule is the major constituent of the extracellular fibril. Since both PrP and A4 are derived from membrane glycoproteins, the elucidation of their normal function is likely to lead to a better understanding of the spongiform and amyloidogenic lesions in these diseases.
- Subjects :
- Alzheimer Disease complications
Amyloid classification
Amyloidosis complications
Amyloidosis metabolism
Creutzfeldt-Jakob Syndrome complications
Humans
Kuru complications
Alzheimer Disease pathology
Amyloid biosynthesis
Amyloidosis pathology
Brain pathology
Creutzfeldt-Jakob Syndrome pathology
Kuru pathology
Subjects
Details
- Language :
- English
- ISSN :
- 0300-5208
- Volume :
- 135
- Database :
- MEDLINE
- Journal :
- Ciba Foundation symposium
- Publication Type :
- Academic Journal
- Accession number :
- 3044707
- Full Text :
- https://doi.org/10.1002/9780470513613.ch3