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Activation of macrophages by Alzheimer beta amyloid peptide
A Klegeris1, D G Walker, P L McGeer
1Kinsmen Laboratory of Neurological Research, Department of Psychiatry, University of British Columbia, Vancouver, Canada.
Abstract:
Microglia (brain resident macrophages) have been found to be closely associated with beta amyloid containing plaques in brain tissue affected by Alzheimer disease (AD). To investigate whether beta amyloid peptide (beta AP) may activate microglia, the effects of synthetic beta AP (amino acids 1-40) and a subfragment (amino acids 25-35) on rat peritoneal macrophages were assessed using four different assays for activation. These peptides were compared with substance P, which has previously been shown to activate macrophages. Both beta amyloid peptides activated macrophages, as assessed by increased respiratory burst-associated oxygen consumption, by luminol-dependent chemiluminescence, and by aggregation. In addition, beta amyloid peptide (1-40) caused a significant increase in macrophage nitric oxide production, while subfragment (25-35) did not. Substance P caused significant activation as assessed by oxygen consumption and chemiluminescence, but not by aggregation or nitric oxide induction.
Insights
Beta amyloid peptides, implicated in Alzheimer disease (AD), activate microglia, the brain's immune cells. This study demonstrates beta amyloid's direct role in triggering microglial activation, a key process in AD pathogenesis.
Area of Science:
- Neuroscience
- Immunology
- Biochemistry
Background:
- Microglia, brain-resident macrophages, are associated with beta-amyloid plaques in Alzheimer disease (AD).
- The direct effect of beta-amyloid peptides on microglial activation is not fully understood.
Purpose of the Study:
- To investigate whether beta-amyloid peptide (beta AP) can activate microglia.
- To compare the activation potential of beta AP with substance P.
Main Methods:
- Synthetic beta AP (amino acids 1-40) and a subfragment (amino acids 25-35) were tested on rat peritoneal macrophages.
- Macrophage activation was assessed using assays for respiratory burst oxygen consumption, chemiluminescence, aggregation, and nitric oxide production.
Main Results:
- Both beta AP (1-40) and its subfragment (25-35) activated macrophages, indicated by increased oxygen consumption, chemiluminescence, and aggregation.
- Beta AP (1-40) significantly increased nitric oxide production, while the subfragment (25-35) did not.
- Substance P activated macrophages via oxygen consumption and chemiluminescence but not aggregation or nitric oxide induction.
Conclusions:
- Beta-amyloid peptides directly activate macrophages, suggesting a role in the inflammatory response in Alzheimer disease.
- The findings highlight beta-amyloid's potential to modulate microglial function, contributing to AD pathology.