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Molecular and cellular characterization of the membrane attack complex, C5b-9, in Alzheimer's disease
S Webster1, L F Lue, L Brachova
1Department of Molecular Biology and Biochemistry, University of California, Irvine 92697, USA.
Insights
The membrane attack complex (MAC, C5b-9) is significantly elevated in Alzheimer's disease brains, indicating its role in neuroinflammation. This complement component is linked to key Alzheimer's pathology markers.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- The membrane attack complex (MAC), C5b-9, is a crucial effector of the complement system in inflammatory responses.
- MAC is the terminal, cytolytic component of both classical and alternative complement pathways, associated with other inflammatory mediators.
Purpose of the Study:
- To investigate the presence and localization of the membrane attack complex (C5b-9) in Alzheimer's disease (AD) brains compared to non-demented (ND) elderly brains.
- To characterize the C5b-9 and its C9 component in AD and ND brains using various molecular and microscopic techniques.
Main Methods:
- Immunohistochemistry (light and electron microscopy)
- Western blot analysis
- Reverse transcriptase polymerase chain reaction (RT-PCR)
- ELISA assays for in vitro C5b-9 production
Main Results:
- MAC (C5b-9) was abundantly present in the Alzheimer's disease cortex, associated with neurofibrillary tangles, dystrophic neurites in plaques, and neuropil threads.
- MAC was weakly detected, if at all, in the cortex of non-demented elderly individuals under identical conditions.
- Specificity of staining was confirmed by antibody deletion and preabsorption.
Conclusions:
- The membrane attack complex (C5b-9) is a significant component of the inflammatory process in Alzheimer's disease brain.
- The findings suggest a potential role for complement-mediated inflammation in AD pathogenesis.
Abstract:
The membrane attack complex, C5b-9, is of considerable importance in many inflammatory reactions. It is the terminal, cytolytic component of both classical and alternative pathway activation, and its presence presupposes other potentially destructive complement constituents, including anaphylotoxins and opsonins. We have characterized C5b-9 and its C9 constituent in the Alzheimer's disease (AD) and nondemented elderly (ND) brain using immunohistochemistry at the light and electron microscopic levels, Western blot analysis, and the reverse transcriptase polymerase chain reaction. We have also conducted in vitro ELISA assays of amyloid beta-peptide-stimulated SC5b-9 production. C5b-9 is abundantly present in Alzheimer's disease cortex, associated with neurofibrillary tangle containing neurons, dystrophic neurites within neuritic plaques, and neuropil threads, but is weakly detected, if at all, in nondemented elderly cortex under the same conditions. Staining of Alzheimer's disease sections is abolished both by deletion of primary antibody or preabsorption with purified SC5b-9.