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Complement-dependent Proinflammatory Properties of the Alzheimer's Disease β-Peptide
Open accessAbstract
Large numbers of neuritic plaques (NP), largely composed of a fibrillar insoluble form of the β-amyloid peptide (Aβ), are found in the hippocampus and neocortex of Alzheimer's disease (AD) patients in association with damaged neuronal processes, increased numbers of activated astrocytes and microglia, and several proteins including the components of the proinflammatory complement system. These studies address the hypothesis that the activated complement system mediates the cellular changes that surround fibrillar Aβ deposits in NP. We report that Aβ peptides directly and independently activate the alternative complement pathway as well as the classical complement pathway; trigger the formation of covalent, ester-linked complexes of Aβ with activation products of the third complement component (C3); generate the cytokine-like C5a complement-activation fragment; and mediate formation of the proinflammatory C5b-9 membrane attack complex, in functionally active form able to insert into and permeabilize the membrane of neuronal precursor cells. These findings provide inflammation-based mechanisms to account for the presence of complement components in NP in association with damaged neurons and increased numbers of activated glial cells, and they have potential implications for the therapy of AD.
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“Fourth, C5b-9 insertion into cell membranes provides an explanation for the association of this complex with dystrophic neurites in NP (2, 3).”
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“In this regard, we and others previously showed that fibrillar forms of A b bound the first reacting factor of the classical complement pathway (CCP), C1q (3, 7), and depleted the activity of the fourth complement component (C4) as well as whole complement activity (CH50), when incubated with human serum as a compleme…”
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Metadata
- Authors
- Bradt, B. M., Kolb, W. P., & Cooper, N. R.
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 1998-08-03
- Volume
- 188
- Issue
- 3
- Pages
- 431-438
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W1967176607
- Cited by
- 255
- References
- 4
- FWCI
- 8.23
- Type
- journal article
- Language
- en
- Open access
- green
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