Serum amyloid P component prevents proteolysis of the amyloid fibrils of Alzheimer disease and systemic amyloidosis
Open accessAbstract
Extracellular deposition of amyloid fibrils is responsible for the pathology in the systemic amyloidoses and probably also in Alzheimer disease [Haass, C. & Selkoe, D. J. (1993) Cell 75, 1039-1042] and type II diabetes mellitus [Lorenzo, A., Razzaboni, B., Weir, G. C. & Yankner, B. A. (1994) Nature (London) 368, 756-760]. The fibrils themselves are relatively resistant to proteolysis in vitro but amyloid deposits do regress in vivo, usually with clinical benefit, if new amyloid fibril formation can be halted. Serum amyloid P component (SAP) binds to all types of amyloid fibrils and is a universal constituent of amyloid deposits, including the plaques, amorphous amyloid beta protein deposits and neurofibrillary tangles of Alzheimer disease [Coria, F., Castano, E., Prelli, F., Larrondo-Lillo, M., van Duinen, S., Shelanski, M. L. & Frangione, B. (1988) Lab. Invest. 58, 454-458; Duong, T., Pommier, E. C. & Scheibel, A. B. (1989) Acta Neuropathol. 78, 429-437]. Here we show that SAP prevents proteolysis of the amyloid fibrils of Alzheimer disease, of systemic amyloid A amyloidosis and of systemic monoclonal light chain amyloidosis and may thereby contribute to their persistence in vivo. SAP is not an enzyme inhibitor and is protective only when bound to the fibrils. Interference with binding of SAP to amyloid fibrils in vivo is thus an attractive therapeutic objective, achievement of which should promote regression of the deposits.
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Serum amyloid P was suggested to contribute to the persistence of amyloid deposits.
“serum amyloid P, the major APP in mice, was suggested to contribute to the persistence of amyloid deposits (Tennent et al., 1995).”
From Model Based Targeting of IL-6-Induced Inflammatory Responses in Cultured Primary Hepatocytes to Improve Application of the JAK Inhibitor Ruxolitinib (2017) · cites this paper as Tennent et al., 1995
The binding of SAP stabilizes amyloid fibrils and promotes their formation in the brain, thereby contributing to the pathogenesis of AD and cerebral amyloid angiopathy.
“The binding of SAP stabilizes amyloid fibrils85 and promotes their formation in the brain86,87, thereby contributing to the pathogenesis of AD and cerebral amyloid angiopathy88,89.”
From Serum amyloid P secreted by bone marrow adipocytes drives skeletal amyloidosis (2025) · cites this paper as [85]
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Research works printed but not linked: 6
- [1]Pepys, M. B. (1994) in Samter's Immunologic Diseases, eds. Frank, M. M., Austen, K. F., Claman, H. N. & Unanue, E. R. (Little, Brown, Boston), 5th Ed., pp. 637–655.
- [5]Maggio, J. E., Stimson, E. R., Ghilardi, J. R., Allen, C. J., Dahl, C. E., Whitcomb, D. C., Vigna, S. R., Vinters, H. V., Labenski, M. E. & Mantyh, P. W. (1992) Proc. Natl. Acad. Sci. USA 89, 5462–5466.
- [16]Skinner, M., Pepys, M. B., Cohen, A. S., Heller, L. M. & Lian, J. B. (1980) in Amyloid and Amyloidosis, eds. Glenner, G. G., Pinho e Costa, P. & Falcao de Freitas, F. (Excerpta Medica, Amsterdam), pp. 384–391.
- [21]Pepys, M. B. (1986) in Amyloidosis, eds. Marrink, J. & van Rijswijk, M. H. (Nijhoff, Dordrecht, The Netherlands), pp. 43– 50.
- [23]Pepys, M. B., Rademacher, T. W., Amatayakul-Chantler, S., Williams, P., Noble, G. E., Hutchinson, W. L., Hawkins, P. N., Nelson, S. R., Gallimore, J. R., Herbert, J., Hutton, T. & Dwek, R. A. (1994) Proc. Natl. Acad. Sci. USA 91, 5602–5606.
- [30]Soutar, A. K., Hawkins, P. N., Vigushin, D. M., Tennent, G. A., Booth, S. E., Hutton, T., Nguyen, O., Totty, N. F., Feest, T. G., Hsuan, J. J. & Pepys, M. B. (1992) Proc. Natl. Acad. Sci. USA 89, 7389-7393.
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“SAP is a universal constituent of amyloid deposits and protects amyloid fibers from proteolysis and subsequent clearance [3].”
Background
- Authors
- Tennent, G. A., Lovat, L. B., & Pepys, M. B.
- Affiliations
- Hammersmith Hospital (GB)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1995-05-09
- Volume
- 92
- Issue
- 10
- Pages
- 4299-4303
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC41931
- OpenAlex
- W2061033316
- Cited by
- 438
- References
- 0
- Citations by year
- 2026: 7 · 2025: 14 · 2024: 13 · 2023: 10 · 2022: 16 · 2021: 12 · 2020: 14 · 2019: 9 · 2018: 8 · 2017: 10 · 2016: 12 · 2015: 20 · 2014: 10 · 2013: 17 · 2012: 26
- FWCI
- 13.08
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Amyloidosis: Diagnosis, Treatment, Outcomes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
- Keywords
- serum amyloid P component, amyloid fibrils, proteolysis, Alzheimer's disease, systemic amyloidosis, amyloid A amyloidosis, amyloid binding, amyloid plaques, amyloid-beta, neurofibrillary tangles, type 2 diabetes
- MeSH terms
- Alzheimer Disease, Amyloid, Serum Amyloid A Protein, Amyloidosis, Chymotrypsin, Galactose, Humans, Kinetics, Protein Binding, Spleen, Trypsin, Amyloid beta-Protein Precursor, Neurofibrillary Tangles
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