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PMID: 7753801 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Serum amyloid P component prevents proteolysis of the amyloid fibrils of Alzheimer disease and systemic amyloidosis.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 92 ·No. 10 ·1995-05-09 ·Pages 4299-303

Tennent GA, Lovat LB, Pepys MB

Abstract

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.

MeSH Terms
Alzheimer Disease/metabolism Amyloid/metabolism Amyloid beta-Protein Precursor/metabolism Amyloidosis/metabolism Chymotrypsin/metabolism Galactose/analogs & derivatives,pharmacology Humans Kinetics Neurofibrillary Tangles/metabolism Protein Binding Serum Amyloid A Protein/metabolism Spleen/metabolism Trypsin/metabolism
Chemicals
Amyloid Amyloid beta-Protein Precursor Serum Amyloid A Protein 4,6-pyruvylated galactose Chymotrypsin Trypsin Galactose
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Tennent G A
Immunological Medicine Unit, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.
Lovat L B
Pepys M B
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.92.10.4299
Published
1995-05-09
Pages
4299-303
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC41931
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.92.10.4299 PMC Full Text View journal details
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