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Nucleoside diphosphatase (NDPase) activity associated with human beta-protein amyloid fibers
H M Wisniewski1, A W Vorbrodt, M H Epstein
1New York State Office of Mental Retardation and Developmental Disabilities, Institute for Basic Research in Developmental Disabilities, Staten Island 10314.
Abstract:
Nucleoside diphosphatase (NDPase) activity was studied by electron microscope cytochemistry in surgical specimens obtained from aged human cerebral cortices. The presence of NDPase activity on the surface of the microglial cells (MCs) and especially within the endoplasmic reticulum (ER) cisternae that are filled with amyloid fibers and that are in continuity with the extracellular amyloid deposits in plaques suggests a possible role of this enzyme in final elaboration of amyloid protein. The close structural relationship between MCs and amyloid plaques, suggesting the participation of these cells in the synthesis or final elaboration of amyloid fibers, was observed. The comparison of these observations with previously reported data on the distribution of NDPase in MCs and amyloid fibers in scrapie-infected mouse brain suggests that presumably similar mechanisms are acting in both cases. These observations, as compared with the results of other cytochemical and biochemical studies, also suggest that co-localization of NDPase activity with newly formed amyloid fibers in plaques can be associated with glycosyltransferase activities engaged in the amyloid or amyloid precursor protein glycosylation.
Insights
Nucleoside diphosphatase (NDPase) activity in aged human brain microglial cells (MCs) suggests a role in amyloid protein elaboration. Similar mechanisms may be involved in scrapie, linking NDPase to amyloid glycosylation.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Microglial cells (MCs) are implicated in brain aging and neurodegenerative diseases.
- Amyloid plaques are a hallmark of Alzheimer's disease and other amyloidopathies.
- Nucleoside diphosphatase (NDPase) is an enzyme with diverse cellular functions.
Purpose of the Study:
- To investigate the role of NDPase in the context of amyloid plaque formation in aged human cerebral cortices.
- To explore the relationship between microglial cells, amyloid fibers, and NDPase activity.
- To compare findings in human brain with those in scrapie-infected mouse models.
Main Methods:
- Electron microscope cytochemistry was employed on surgical specimens of aged human cerebral cortices.
- Localization of NDPase activity was examined at the cellular and subcellular levels.
- Observations were compared with existing data from scrapie-infected mouse brains.
Main Results:
- NDPase activity was detected on the surface of microglial cells (MCs).
- Significant NDPase activity was found within endoplasmic reticulum (ER) cisternae containing amyloid fibers, continuous with extracellular deposits.
- A close structural association between MCs and amyloid plaques was observed, suggesting MCs' involvement in amyloid elaboration.
Conclusions:
- NDPase may play a role in the final elaboration of amyloid protein in the human brain.
- Similar mechanisms involving NDPase and microglial cells might be conserved across species and diseases, including scrapie.
- The co-localization of NDPase with amyloid fibers suggests a potential link to glycosyltransferase activities involved in amyloid or amyloid precursor protein glycosylation.