Amyloid Plaques Dissociate Pentameric to Monomeric C‐Reactive Protein: A Novel Pathomechanism Driving Cortical Inflammation in Alzheimer's Disease?
Open accessAbstract
Beta‐amyloid (Aβ) plaques and local inflammation are central to the pathogenesis of Alzheimer's disease. Although an association between circulating pentameric C‐reactive protein (pCRP) and Alzheimer's disease has been reported no pathomechanistic link has been established. We hypothesized that Aβ plaques induce the dissociation of pCRP to individual monomers (mCRP), which possess strong pro‐inflammatory properties not shared with pCRP and localizing inflammation to Alzheimer's plaques. pCRP was incubated with Aβ plaques generated in vitro and with non‐aggregated Aβ 42 peptide. pCRP dissociation to mCRP was found only when co‐incubated with Aβ plaques. Furthermore, sections of frontal cortex from brains of patients with and without Alzheimer's disease were stained with antibodies specific for mCRP and pCRP. There was significantly more mCRP in the cortex of Alzheimer's disease patients (P ≤ 0.01). In contrast, there was no significant difference in pCRP staining. These findings establish that Aβ plaques possess a previously unrecognized potential to dissociate pentameric CRP to monomeric CRP. The existence of mCRP but not pCRP in the brains of Alzheimer's disease patients strongly indicates that this newly described biological effect of Aβ plaques is relevant in Alzheimer pathobiology; potentially localizing and amplifying inflammation via the strong pro‐inflammatory effects of locally generated mCRP.
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Pentameric CRP dissociation into monomeric forms is prompted by amyloid plaque in APP/PS1 mice.
“The CRP has a role in amyloid pathology as studied and shown in APP/PS1 (amyloid precursor protein/presenilin 1) mice; pentameric CRP dissociation takes place into monomeric forms prompted by amyloid plaque [50, 51].”
From Recent Advancements in Pathogenesis, Diagnostics and Treatment of Alzheimer’s Disease (2020) · cites this paper as [50]
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Recent Advancements in Pathogenesis, Diagnostics and Treatment of Alzheimer’s Disease
Khan, S., Barve, K. H., & Kumar, M. S. (2020) · Current Neuropharmacology · doi:10.2174/1570159x18666200528142429 · Cited by 820 · see citing works
“The CRP has a role in amyloid pathology as studied and shown in APP/PS1 (amyloid precursor protein/presenilin 1) mice; pentameric CRP dissociation takes place into monomeric forms prompted by amyloid plaque [50, 51].”
BackgroundOxidative Stress, Inflammation, and Neuroprogression in Chronic PTSD
Miller, M. W., Lin, A. P., Wolf, E. J., & Miller, D. R. (2018) · Harvard Review of Psychiatry · doi:10.1097/hrp.0000000000000167 · Cited by 237 · see citing works
Brosseron, F., Traschütz, A., Widmann, C. N., Kummer, M. P., Tacik, P., Santarelli, F., Jessen, F., & Heneka, M. T. (2018) · Alzheimer's Research & Therapy · doi:10.1186/s13195-018-0353-3 · Cited by 113 · see citing works
“have described dissociation of pentameric into monomeric CRP induced by amyloid plaques [28, 29].”
BackgroundSlevin, M., Matou, S., Zeinolabediny, Y., Corpas, R., Weston, R., Liu, D., Boras, E., Di Napoli, M., Petcu, E., Sarroca, S., et al. (2015) · Scientific Reports · doi:10.1038/srep13281 · Cited by 115 · see citing works
- Authors
- Strang, F., Scheichl, A., Chen, Y., Wang, X., Htun, N., Bassler, N., Eisenhardt, S. U., Habersberger, J., & Peter, K.
- Affiliations
- Baker Heart and Diabetes Institute (AU)
- Venue
- Brain Pathology
- Publisher
- Wiley
- Published
- 2011-11
- Volume
- 22
- Issue
- 3
- Pages
- 337-346
- ISSN
- 1015-6305 (ISSN-L)
- 1750-3639
- PMC
- PMC8092962
- OpenAlex
- W1926292724
- Cited by
- 94
- References
- 42
- Citations by year
- 2026: 3 · 2025: 11 · 2024: 4 · 2023: 7 · 2022: 8 · 2021: 7 · 2020: 7 · 2019: 6 · 2018: 12 · 2017: 5 · 2016: 6 · 2015: 6 · 2014: 5 · 2013: 2 · 2012: 5
- FWCI
- 2.62
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain Pathology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Monash University
- Australian Research Council
- National Health and Medical Research Council
- National Medical Research Council
- DOD Prostate Cancer Research Program
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Biomarkers in Disease Mechanisms
- Keywords
- Alzheimer's disease, amyloid plaques, C-reactive protein, monomeric C-reactive protein, cortical inflammation, inflammatory cytokines, amyloid-beta, frontal cortex
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Brain, C-Reactive Protein, Female, Humans, Inflammation, Male, Plaque, Amyloid
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