Serum Amyloid P Component Accelerates the Formation and Enhances the Stability of Amyloid Fibrils in a Physiologically Significant Under-Saturated Solution of Amyloid-β42
Abstract
The mechanism whereby an under-saturated solution of amyloid-β (Aβ)42 precipitates as β sheets in vivo in Alzheimer's disease remains to be elucidated. Herein we present in vitro evidence that serum amyloid P component may mediate this process through its acceleration of amyloid formation from an under-saturated solution of Aβ42 and subsequently its stabilization of the amyloid fibrils formed over physiologically significant timeframes. Our observations support serum amyloid P component as a therapeutic target in Alzheimer's disease.
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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 [86]
Cites
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Self-citationCopper Abolishes the β-Sheet Secondary Structure of Preformed Amyloid Fibrils of Amyloid-β42
House, E., Mold, M., Collingwood, J., Baldwin, A., Goodwin, S., & Exley, C. (2009) · Journal of Alzheimer's Disease · doi:10.3233/jad-2009-1235 · Cited by 45 · see citing works
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Extracellular protein components of amyloid plaques and their roles in Alzheimer’s disease pathology
Rahman, M. M., & Lendel, C. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00465-0 · Cited by 245 · see citing works
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“Recent studies show that SAP accelerates the formation and enhances the proteolytic stability of A 42 fibrils (73).”
BackgroundMold, M., Ouro-Gnao, L., Wieckowski, B. M., & Exley, C. (2013) · Scientific Reports · doi:10.1038/srep01256 · Cited by 101 · see citing works
Self-citationPlasma Based Markers of [11C] PiB-PET Brain Amyloid Burden
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Blood-Derived Plasma Protein Biomarkers for Alzheimer’s Disease in Han Chinese
Cheng, Z., Yin, J., Yuan, H., Jin, C., Zhang, F., Wang, Z., Liu, X., Wu, Y., Wang, T., & Xiao, S. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00414 · Cited by 37 · see citing works
“…been considered to be interesting and potentially significant in AD disease pathology in previous studies (Phillips et al., 1991; Iadecola and Davisson, 2008; Carecchio and Comi, 2011; Daborg et al., 2012; Mold et al., 2012; Tian et al., 2014; Willette et al., 2015; Buxbaum and Johansson, 2017).”
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Greene, M., Klimtchuk, E. S., Seldin, D. C., Berk, J. L., & Connors, L. H. (2014) · Biochemistry · doi:10.1021/bi5011249 · Cited by 26 · see citing works
HIV Infection Induces Extracellular Cathepsin B Uptake and Damage to Neurons
Cantres-Rosario, Y. M., Ortiz-Rodríguez, S. C., Santos-Figueroa, A. G., Plaud, M., Negrón, K., Cotto, B., Langford, D., & Meléndez, L. M. (2019) · Scientific Reports · doi:10.1038/s41598-019-44463-1 · Cited by 35 · see citing works
Ozawa, D., Nomura, R., Mangione, P. P., Hasegawa, K., Okoshi, T., Porcari, R., Bellotti, V., & Naiki, H. (2016) · Scientific Reports · doi:10.1038/srep29077 · Cited by 25 · see citing works
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Luo, J., Wärmländer, S., Gräslund, A., & Abrahams, J. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.a116.714576 · Cited by 24
“Recent studies show that SAP accelerates the formation and enhances the proteolytic stability of A 42 fibrils (73).”
BackgroundWallin, C., Luo, J., Jarvet, J., Wärmländer, S. K. T. S., & Gräslund, A. (2016) · Israel Journal of Chemistry · doi:10.1002/ijch.201600105 · Cited by 24 · see citing works
Lin, X.-Y., Pan, D., Sang, L.-X., & Chang, B. (2021) · World Journal of Gastroenterology · doi:10.3748/wjg.v27.i12.1132 · Cited by 18 · see citing works
Serum amyloid P secreted by bone marrow adipocytes drives skeletal amyloidosis
Kumar, S., Song, K., Wang, J., Baghel, M. S., Zeng, Y., Shen, K., Zheng, J., Crane, J., Demehri, S., Gao, P., et al. (2025) · Nature Aging · doi:10.1038/s43587-025-00924-z · Cited by 16 · see citing works
“The binding of SAP stabilizes amyloid fibrils 85 and promotes their formation in the brain 86,87 , thereby contributing to the pathogenesis of AD and cerebral amyloid angiopathy 88,89 .”
Genetic evidence for serum amyloid P component as a drug target in neurodegenerative disorders
Schmidt, A. F., Finan, C., Chopade, S., Ellmerich, S., Rossor, M. N., Hingorani, A. D., & Pepys, M. B. (2024) · Open Biology · doi:10.1098/rsob.230419 · Cited by 11 · see citing works
Intracellular tracing of amyloid vaccines through direct fluorescent labelling
Mold, M. J., Kumar, M., Mirza, A., Shardlow, E., & Exley, C. (2018) · Scientific Reports · doi:10.1038/s41598-018-20845-9 · Cited by 7 · see citing works
Self-citationSerum amyloid P component accumulates and persists in neurones following traumatic brain injury
Yip, P. K., Liu, Z.-H., Hasan, S., Pepys, M., & Uff, C. E. G. (2023) · Open Biology · doi:10.1098/rsob.230253 · Cited by 4 · see citing works
“The binding of SAP stabilizes amyloid fibrils [30] and promotes their formation [31,32], thereby contributing to both amyloid deposition and persistence [33].”
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Schmidt, A. F., Finan, C., Chopade, S., Ellmerich, S., Rossor, M. N., Hingorani, A. D., & Pepys, M. B. (2023) · medRxiv · doi:10.1101/2023.08.15.23293564 · Cited by 4 · see citing works
Bergkvist, L. (2017) · Linköping studies in science and technology. Dissertations · doi:10.3384/diss.diva-137452
“These mutations often result in an increased Aβ1-42/Aβ1-40 concentration ratio (Scheuner et al., 1996).”
BackgroundInfluential
- Authors
- Mold, M., Shrive, A. K., & Exley, C.
- Affiliations
- Keele University (GB)
- Venue
- Journal of Alzheimer's Disease
- Publisher
- SAGE Publications
- Published
- 2012-04-16
- Volume
- 29
- Issue
- 4
- Pages
- 875-881
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W1553593663
- Cited by
- 26
- References
- 0
- Citations by year
- 2025: 3 · 2024: 1 · 2023: 3 · 2021: 4 · 2020: 1 · 2019: 1 · 2018: 3 · 2016: 4 · 2015: 2 · 2014: 1 · 2013: 2 · 2012: 1
- FWCI
- 1.29
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
- Keywords
- serum amyloid P component, amyloid-beta 42
- MeSH terms
- Aluminum, Amyloid, Serum Amyloid P-Component, Animals, Calcium, Copper, Dose-Response Relationship, Drug, Glucose, Humans, Magnesium, Peptide Fragments, Time Factors, Tomography, X-Ray Computed, Tromethamine, Amyloid beta-Peptides, Protein Structure, Secondary
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