The DOI matches its Crossref record; 93 of the 93 references it cites were found in a registry or an index.
Complement in the pathogenesis of Alzheimer’s disease
Open accessAbstract
The emergence of complement as an important player in normal brain development and pathological remodelling has come as a major surprise to most scientists working in neuroscience and almost all those working in complement. That a system, evolved to protect the host against infection, should have these unanticipated roles has forced a rethink about what complement might be doing in the brain in health and disease, where it is coming from, and whether we can, or indeed should, manipulate complement in the brain to improve function or restore homeostasis. Complement has been implicated in diverse neurological and neuropsychiatric diseases well reviewed elsewhere, from depression through epilepsy to demyelination and dementia, in most complement drives inflammation to exacerbate the disease. Here, I will focus on just one disease, the most common cause of dementia, Alzheimer's disease. I will briefly review the current understanding of what complement does in the normal brain, noting, in particular, the many gaps in understanding, then describe how complement may influence the genesis and progression of pathology in Alzheimer's disease. Finally, I will discuss the problems and pitfalls of therapeutic inhibition of complement in the Alzheimer brain.
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“Recently, a number of novel agents targeting the complement system are being developed and tested in clinical trials for potential effective therapy for AD [97].”
From Sex-specific DNA methylation differences in Alzheimer’s disease pathology (2021) · cites this paper as [97]
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“Strong evidence has implicated the complement system in the pathogenesis of Alzheimer’s disease [72–76]”
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“Inappropriate control of the classical complement cascade causes unresolvable inflammation and disease (Hong et al. , 2016; Hansen, Hanson and Sheng, 2018; Morgan, 2018).”
From Spatial Transcriptomics and In Situ Sequencing to Study Alzheimer’s Disease (2020) · cites this paper as Morgan, 2018
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Meta-Analysis of 74,046 Individuals Identifies 11 New Susceptibility Loci for Alzheimer’s Disease
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Complement and microglia mediate early synapse loss in Alzheimer mouse models
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“In the hAPP model, C1q labelling of synapses was seen early and in much higher amounts than in normal mice; inhibition of C1q using a blocking antibody or deficiency of either C1q or C3 reduced synaptic elimination and improved hippocampal function [59].”
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Additional file 2 of An integrated toolkit for human microglia functional genomics
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Dysregulation of complement at the synapse in P301S mice and human tauopathies
Nimmo, J., Daskoulidou, N., Pottelberge, S. V., Muynck, L. D., & Morgan, B. P. (2026) · Acta Neuropathologica Communications · doi:10.1186/s40478-026-02347-2
Self-citationGiffin, K. A., Puranik, N., Bustamante, A. C., Padilla, M., Zeng, Z., Randolph, G., Wheaton, L., Moore, S. J., Newstead, M. W., Denstaedt, S. J., et al. (2026) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2026.101309
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Metadata
- Authors
- Morgan, B. P.
- Affiliations
- Cardiff University (GB)
- Corresponding author
- Morgan, B. Paul
- ORCID
- Morgan, B. Paul
- Venue
- Seminars in Immunopathology
- Published
- 2017-11-13
- Volume
- 40
- Issue
- 1
- Pages
- 113-124
- ISSN
- 1863-2297 (ISSN-L)
- 1863-2300
- PMC
- PMC5794825
- OpenAlex
- W2769984699
- Cited by
- 194
- References
- 93
- Citations by year
- 2026: 14 · 2025: 16 · 2024: 35 · 2023: 16 · 2022: 18 · 2021: 32 · 2020: 31 · 2019: 22 · 2018: 10
- FWCI
- 1.77
- Type
- journal article
- Language
- en
- Update notices
- correction (2018-09-21)
- Open access
- hybrid
- doi.org
- Locations
- Seminars in Immunopathology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
- Funders
- Cardiff University
- 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
- complement system, Alzheimer's disease, complement inhibition therapy, neuroinflammation, brain homeostasis, dementia pathogenesis
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