Preferential association of serum amyloid P component with fibrillar deposits in familial British and Danish dementias: similarities with Alzheimer's disease.

Abstract

Two hereditary forms of cerebrovascular amyloidosis, familial British and Danish dementias (FBD and FDD), share striking similarities with Alzheimer's disease (AD) despite structural differences among their amyloid subunits (ABri in FBD, ADan in FDD, and Abeta in AD). Neuropathological lesions in these disorders include neurofibrillary tangles, parenchymal amyloid and pre-amyloid deposits and overwhelming cerebral amyloid angiopathy co-localizing with reactive microglia and multiple amyloid associated proteins including activation products of the complement cascade. Immunohistochemical analysis of FBD and FDD brain lesions unveiled the presence of serum amyloid P-component (SAP) primarily associated with thioflavin positive amyloid deposits in spite of the significant pre-amyloid burden existing in both disorders. Using affinity chromatography and ELISA binding assays we demonstrated specific, calcium-dependent, saturable, high affinity binding interactions between SAP and ABri/ADan peptides, with dissociation constant values in the sub-nanomolar range and within the same order of magnitude as those resulting from the interaction of SAP with Alzheimer's Abeta1-40 and Abeta1-42. The preferential association of SAP with fibrillar amyloid lesions and not with non-fibrillar pre-amyloid deposits is puzzling, suggesting that SAP modulates the assembly and stability of the final fibril rather than participating in the early steps of protein misfolding and oligomerization.

• Authors: Agueda Rostagno, Tammaryn Lashley, Douglas Ng, Jordana Meyerson, Hans Braendgaard, Gordon Plant, Marie Bojsen-Møller, Janice Holton, Blas Frangione, Tamas Revesz, Jorge Ghiso
• Journal: Journal of the neurological sciences (J Neurol Sci) Vol. 257 Issue 1-2 Pg. 88-96 (Jun 15 2007) ISSN: 0022-510X [Print] Netherlands
• PMID: 17374542 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Adaptor Proteins, Signal Transducing
• Amyloid
• Amyloid beta-Peptides
• Benzothiazoles
• Biomarkers
• ITM2B protein, human
• Membrane Glycoproteins
• Membrane Proteins
• Peptide Fragments
• Protein Subunits
• Serum Amyloid P-Component
• Thiazoles
• amyloid beta-protein (1-40)
• amyloid beta-protein (1-42)
• thioflavin T

Topics

• Adaptor Proteins, Signal Transducing
• Aged
• Amyloid (metabolism)
• Amyloid beta-Peptides (metabolism)
• Benzothiazoles
• Biomarkers (metabolism)
• Brain (metabolism, pathology, physiopathology)
• Cerebral Amyloid Angiopathy, Familial (metabolism, pathology, physiopathology)
• Dementia (metabolism, pathology, physiopathology)
• Denmark
• England
• Humans
• Immunohistochemistry
• Membrane Glycoproteins
• Membrane Proteins
• Neurofibrils (metabolism, pathology)
• Peptide Fragments (metabolism)
• Plaque, Amyloid (metabolism, pathology)
• Protein Subunits (metabolism)
• Serum Amyloid P-Component (metabolism)
• Thiazoles (metabolism)