Complement activation in very early Alzheimer disease
Abstract
The activation of the classical complement (C)-system in early-stage Alzheimer disease (AD) and nondemented aging was examined with immunohistochemistry in subjects assessed by the Clinical Dementia Rating (CDR). Activation (staining for C3 and C4 fragments) was found in all brains with amyloid deposits, including all nondemented (CDR 0) cases, with either small numbers of diffuse plaques or with sufficient plaques and tangles to indicate preclinical AD. Staining for C3 and C4 increased in parallel with plaque density in very mild to severe clinical AD. A subset of very mild AD (CDR 0.5) cases also showed C1q (on plaques) and C5b-9 (on neuritic plaques and tangles), whereas these C-fragments were consistently found in severe AD (CDR 3). Mirror section (split-face) analysis showed that C1q, C3, and apoJ (clusterin) occurred on the same plaques. However, C-system regulators CD59, CR1, DAF, and MCP were not detected on plaques or tangles at any stage, indicating that C-activation related to AD is incompletely controlled.
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In human AD brain tissue, there is immunohistochemical evidence for activation of complement, especially associated with plaques (C1q, C3, and C4) and to a lesser extent with neurofibrillary tangles and dystrophic neurites (C5b-C9).
“In human AD brain tissue, there is considerable immunohistochemical evidence for activation of complement, especially associated with plaques (C1q, C3, and C4) and to a lesser extent with neurofibrillary tangles and dystrophic neurites (C5b-C9; Zanjani et al., 2005).”
From Microglia in Alzheimer’s disease (2018) · cites this paper as Zanjani et al., 2005
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Self-citation
- Authors
- Zanjani, H., Finch, C. E., Kemper, C., Atkinson, J., McKeel, D., Morris, J. C., & Price, J. L.
- Affiliations
- University of Southern California (US)
- Washington University in St. Louis (US)
- Corresponding author
- Zanjani, H
- Finch, C E
- Venue
- Alzheimer Disease & Associated Disorders
- Published
- 2005-04
- Volume
- 19
- Issue
- 2
- Pages
- 55-66
- ISSN
- 0893-0341 (ISSN-L)
- OpenAlex
- W2041432038
- Cited by
- 115
- References
- 33
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 1 · 2023: 3 · 2022: 1 · 2021: 9 · 2020: 7 · 2019: 5 · 2018: 6 · 2017: 3 · 2016: 2 · 2015: 6 · 2014: 4 · 2013: 8 · 2012: 6
- FWCI
- 2.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Alzheimer Disease & Associated Disorders (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG03991, AG-13499, AG 05681, R01AG013499, P50AG005681, P01AG003991)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- complement system, Alzheimer's disease, preclinical Alzheimer's disease, amyloid plaques, neurofibrillary tangles, complement C3, C4, C1q, membrane attack complex, clusterin, complement regulatory proteins, CD59, complement receptor 1, CD55, mannose-binding protein, Clinical Dementia Rating
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Analysis of Variance, Complement System Proteins, Female, Humans, Male, Middle Aged, Amyloid beta-Peptides
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