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Astrocytes associated with senile plaques possess muscarinic acetylcholine receptors
E Messamore1, N Bogdanovich, H Schröder
1Karolinska Institute Alzheimer's Disease Research Centre, Department of Geriatric Medicine, Huddinge University Hospital, Sweden.
Abstract:
AUTOPSY sections of the temporal and parahippocampal gyri were incubated with the monoclonal antibody M35 to label muscarinic acetylcholine receptors. Senile plaques were visualized either by counterstaining with Congo red or by Bielschowsky silver-stain of adjacent sections. The antibody labelled pyramidal and non-pyramidal cells in the grey matter, as well as fibrous astrocytes in the white matter and first cortical layer, of elderly control brains. In AD brains however, the grey matter was characterized by prominently labelled fibrous astrocytes and few or poorly labelled neurones. M35-immunoreactive astrocytes were often associated with senile plaques. These findings suggest that plaque-associated astrocytes may be responsive to acetylcholine or cholinergic drugs.
Insights
In Alzheimer's disease (AD) brains, M35 antibody revealed fewer neurons but more fibrous astrocytes, especially near senile plaques. This suggests astrocytes may respond to acetylcholine or related drugs.
Area of Science:
- Neuroscience
- Neuropathology
- Alzheimer's Disease Research
Background:
- Muscarinic acetylcholine receptors are crucial for cognitive function.
- Alterations in neuronal and glial cells are characteristic of Alzheimer's disease (AD).
- Senile plaques are a hallmark pathology in AD brains.
Purpose of the Study:
- To investigate the distribution and characteristics of muscarinic acetylcholine receptors in the temporal and parahippocampal gyri of control and AD brains.
- To explore the relationship between M35-labeled cells, particularly astrocytes, and senile plaques in AD.
Main Methods:
- Autopsy brain sections from elderly controls and AD patients were used.
- Monoclonal antibody M35 was employed to label muscarinic acetylcholine receptors.
- Congo red staining and Bielschowsky silver-stain were utilized to visualize senile plaques.
Main Results:
- In control brains, M35 labeled neurons and fibrous astrocytes in grey and white matter.
- In AD brains, M35 prominently labeled fibrous astrocytes, often associated with senile plaques, while neurons were poorly labeled.
- A significant increase in M35-immunoreactive astrocytes was observed in AD grey matter compared to controls.
Conclusions:
- Astrocytes in AD brains exhibit altered muscarinic acetylcholine receptor expression, particularly in proximity to senile plaques.
- Plaque-associated astrocytes may possess functional muscarinic receptors, suggesting potential responsiveness to acetylcholine or cholinergic therapies.
- These findings highlight a potential role for astrocytes in AD pathogenesis and suggest them as therapeutic targets.