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Reactive microglia specifically associated with amyloid plaques in Alzheimer's disease brain tissue express
W A Jefferies1, M R Food, R Gabathuler
1Biotechnology Laboratory, University of British Columbia, Vancouver, Canada.
Abstract:
Several investigations have implicated the involvement of metals in neuropathologies. In particular, the disruption of iron metabolism and iron transport molecules have been demonstrated in Alzheimer's disease (AD). We have identified a novel pathway of iron uptake into mammalian cells involving melanotransferrin, or p97, which is independent of the transferrin receptor. Here we investigated whether there is a possible link between this molecule and the pathology of AD. The distributions of melanotransferrin, transferrin and the transferrin receptor were studied immunohistochemically in brain tissues from AD cases. In brain tissues from AD, melanotransferrin and the transferrin receptor were highly localized to capillary endothelium, while transferrin itself was mainly localized to glial cells. In brain tissue derived from AD patients, melanotransferrin was additionally detected in a subset of reactive microglia associated with senile plaques. Our demonstration that melanotransferrin mediates iron uptake through a pathway independent of the transferrin receptor indicates that this mechanism may have a role in AD.
Insights
Melanotransferrin, a novel iron uptake pathway, may play a role in Alzheimer's disease (AD) pathology. This protein was found in specific brain cells, suggesting a new target for AD research.
Area of Science:
- Neuroscience
- Biochemistry
- Pathology
Background:
- Metals, particularly iron, are implicated in neuropathologies.
- Disruptions in iron metabolism and transport are evident in Alzheimer's disease (AD).
- A novel iron uptake pathway involving melanotransferrin (p97), independent of the transferrin receptor, has been identified.
Purpose of the Study:
- To investigate the potential link between melanotransferrin and Alzheimer's disease (AD) pathology.
- To examine the distribution of melanotransferrin, transferrin, and the transferrin receptor in AD brain tissues.
Main Methods:
- Immunohistochemical analysis of brain tissues from AD cases.
- Localization studies of melanotransferrin, transferrin, and transferrin receptor.
Main Results:
- In AD brain tissues, melanotransferrin and the transferrin receptor were highly localized to capillary endothelium.
- Transferrin was primarily found in glial cells.
- Melanotransferrin was also detected in reactive microglia associated with senile plaques in AD brains.
Conclusions:
- Melanotransferrin mediates iron uptake via a pathway distinct from the transferrin receptor.
- This melanotransferrin-mediated iron uptake pathway may contribute to the pathology of Alzheimer's disease.