alzheimer’s disease (ad) is a neurodegenerative disorder and the most common form of dementia. almost 47 million people suffer from dementia worldwide. ad accounts for approximately 60%–80% of all dementia cases. three major pathologies characterize the disease: senile plaques, neurofibrillary tangles and inflammation. we review the literature on events contributing to the inflammation. those i...

Three potent rabbit antisera to human serum amyloid A protein (SAA) appear to be directed exclusibely to the carboxy terminal region not shared with the tissue amyloid A protein. Since binding to albumin completely blocks the reaction of these antisera with the antigen, and since SAA exists in serum complexed to albumin, the anti-SAA cannot be used to detect or quantitate this serum component. ...

The oligomeric state of human SAP (serum amyloid P component) in the absence and presence of known ligands has been investigated using nanoelectrospray ionization MS. At pH 8.0, in the absence of Ca2+, SAP has been shown to consist of pentameric and decameric forms. In the presence of physiological levels of Ca2+, SAP was observed to exist primarily as a pentamer, reflecting its in vivo state. ...

Solid-phase binding, competitive binding, and cytotoxicity neutralization assays indicate that the B pentamer and A subunit both contribute to human serum amyloid P (HuSAP) component binding to Stx2. A polyvalent globotriaosyl-ceramide receptor analog, Daisy, did not competitively inhibit HuSAP binding, implying that the two ligands bind to different Stx2 domains.

The amyloid deposits that cause disease in systemic amyloidosis always contain the normal plasma protein, serum amyloid P (SAP) component. SAP is the target of a novel immunotherapy approach now being developed to eliminate amyloid deposits. The treatment is enabled by, and critically depends on, the use of the drug (R)-1-[6-[(R)-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine-2-carboxyli...

Wolfson Drug Discovery Unit, Centre for Amyloidosis and Acute Phase Proteins, Division of Medicine, Royal Free Campus, University College London, Rowland Hill Street, London NW3 2PF, UK Division of Neuropathology and Department of Neurodegenerative Disease, and Stroke Research Group, Department of Brain Repair and Rehabilitation, Institute of Neurology, University College London, Queen Square, ...

Insoluble protein fibrils resulting from the self-assembly of a conformational intermediate are implicated as the causative agent in several severe human amyloid diseases, including Alzheimer's disease, familial amyloid polyneuropathy, and senile systemic amyloidosis. The latter two diseases are associated with transthyretin (TTR) amyloid fibrils, which appear to form in the acidic partial dena...

Highly specific, high-resolution scintigraphic images of amyloid-laden organs in mice with experimentally induced amyloid A protein (AA) amyloidosis were obtained after intravenous injection of 123I-labeled serum amyloid P component (SAP). Interestingly, a much higher proportion (up to 40%) of the injected dose of heterologous human SAP localized to amyloid and was retained there than was the c...

Amyloid deposits are proteinaceous extra-cellular aggregates associated with a diverse range of disease states. These deposits are composed predominantly of amyloid fibrils, the unbranched, beta-sheet rich structures that result from the misfolding and subsequent aggregation of many proteins. In addition, amyloid deposits contain a number of non-fibrillar components that interact with amyloid f...