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Activation of the classical complement pathway in brain tissue of Alzheimer patients
Abstract
Positive immunohistochemical staining of Alzheimer brain tissue was obtained with antibodies to proteins associated with classical, but not the alternative, complement pathway. Clq, C3d, C4d are fractions of complement proteins that bind to tissue when the classical complement pathway is activated. Antibodies to these fractions stained senile plaques, dystrophic neurites and some neurofibrillary tangles. C5b-9 is the membrane attack complex which promotes cell lysis when assembled on the plasma membrane. An antibody to a neoantigenic site on this complex stained dystrophic neurites and many neurofibrillary tangles, but not extracellular amyloid. Properdin and fraction Bb of factor B, two proteins that bind to tissue when the alternative complement pathway is activated, were not detected immunohistochemically.
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“in normal aging [300] and in tauopathy patients [75], C1q is dramatically upregulated and is shown to co-localize with hyperphosphorylated tau, plaques and neurofibrillary tangles in AD brain sections [1, 219, 282]”
From Microglia and monocytes in inflammatory CNS disease: integrating phenotype and function (2022) · cites this paper as [219]
In the citing paper
“The classical complement cascade is triggered by C1q-complex, and C1q is strongly expressed by microglia and enriched in the plaque cellular niche, as shown in Figure 4I and S4B (Eikelenboom et al. , 1988; McGeer et al. , 1989).”
From Spatial Transcriptomics and In Situ Sequencing to Study Alzheimer’s Disease (2020) · cites this paper as McGeer et al., 1989
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Metadata
- Authors
- McGeer, P. L., Akiyama, H., Itagaki, S., & McGeer, E. G.
- Affiliations
- University of British Columbia (CA)
- Corresponding author
- McGeer, P.L.
- Venue
- Neuroscience Letters
- Publisher
- Elsevier BV
- Published
- 1989-12
- Volume
- 107
- Issue
- 1-3
- Pages
- 341-346
- ISSN
- 0304-3940 (ISSN-L)
- OpenAlex
- W1980565738
- Cited by
- 383
- References
- 15
- Citations by year
- 2025: 5 · 2024: 10 · 2023: 7 · 2022: 6 · 2021: 12 · 2020: 7 · 2019: 10 · 2018: 8 · 2017: 9 · 2016: 6 · 2015: 8 · 2014: 12 · 2013: 17 · 2012: 10
- FWCI
- 3.94
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience Letters (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- classical complement pathway, Alzheimer's disease, complement activation, C1q, C3d, C4d, C5b-9 membrane attack complex, amyloid plaques, dystrophic neurites, neurofibrillary tangles, amyloid, alternative complement pathway, properdin, factor B
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Brain, Inclusion Bodies, Complement Activation, Complement Pathway, Classical, Complement C4, Humans, Immunohistochemistry, Neurofibrils, Peptide Fragments, Complement C1q, Complement C3d, Complement C4b, Complement Membrane Attack Complex
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