scholarly journals Pharmacological removal of serum amyloid P component from intracerebral plaques and cerebrovascular Aβ amyloid deposits in vivo

Open Biology ◽  
2016 ◽  
Vol 6 (2) ◽  
pp. 150202 ◽  
Author(s):  
Raya Al-Shawi ◽  
Glenys A. Tennent ◽  
David J. Millar ◽  
Angela Richard-Londt ◽  
Sebastian Brandner ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Serum Amyloid ◽  
Amyloid P Component ◽  
Serum Amyloid P ◽  
Serum Amyloid P Component ◽  
Amyloid Deposits ◽  
Amyloid P ◽  
Cerebrovascular Amyloid

Human amyloid deposits always contain the normal plasma protein serum amyloid P component (SAP), owing to its avid but reversible binding to all amyloid fibrils, including the amyloid β (Aβ) fibrils in the cerebral parenchyma plaques and cerebrovascular amyloid deposits of Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA). SAP promotes amyloid fibril formation in vitro , contributes to persistence of amyloid in vivo and is also itself directly toxic to cerebral neurons. We therefore developed (R)-1-[6-[(R)-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine-2-carboxylic acid (CPHPC), a drug that removes SAP from the blood, and thereby also from the cerebrospinal fluid (CSF), in patients with AD. Here we report that, after introduction of transgenic human SAP expression in the TASTPM double transgenic mouse model of AD, all the amyloid deposits contained human SAP. Depletion of circulating human SAP by CPHPC administration in these mice removed all detectable human SAP from both the intracerebral and cerebrovascular amyloid. The demonstration that removal of SAP from the blood and CSF also removes it from these amyloid deposits crucially validates the strategy of the forthcoming ‘Depletion of serum amyloid P component in Alzheimer's disease (DESPIAD)’ clinical trial of CPHPC. The results also strongly support clinical testing of CPHPC in patients with CAA.

Studies with Radiolabelled Serum Amyloid P Component Provide Evidence for Turnover and Regression of Amyloid Deposits In Vivo

1994 ◽  
Vol 87 (3) ◽  
pp. 289-295 ◽  
Author(s):  
Philip N. Hawkins
Keyword(s):  
Amyloid Fibrils ◽  
Specific Binding ◽  
Serum Amyloid ◽  
Poor Correlation ◽  
Amyloid P Component ◽  
Serum Amyloid P ◽  
Serum Amyloid P Component ◽  
Amyloid Deposits ◽  
Amyloid P

1. Quantitative scintigraphic and turnover studies, utilizing the specific binding affinity of serum amyloid P component for amyloid fibrils, have been developed as a tool for evaluating amyloid deposits in vivo. 2. Serial studies in over 300 patients have shown characteristic, diagnostic tissue distributions of amyloid in different types of amyloidosis. There is generally a poor correlation between quantity of amyloid and associated organ dysfunction. 3. Contrary to previous expectations, regression of amyloid has been demonstrated systematically for the first time: AA, AL and variant transthyretin-associated amyloid deposits often regress rapidly, and sometimes completely, if the supply of fibril protein precursors is substantially reduced.

P2-307: CPHPC depletes serum amyloid P component from the cerebrospinal fluid in Alzheimer's disease

2008 ◽  
Vol 4 ◽  
pp. T462-T462
Author(s):  
Basil H. Ridha ◽  
Martin N. Rossor ◽  
Sebastian J. Crutch ◽  
Geoffrey Keir ◽  
J. Ruth Gallimore ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Serum Amyloid ◽  
Amyloid P Component ◽  
Serum Amyloid P ◽  
Serum Amyloid P Component ◽  
Amyloid P

Serum Amyloid P Component Scintigraphy in Alzheimer's Disease

1996 ◽  
Vol 90 (s34) ◽  
pp. 18P-18P
Author(s):  
L B Lovat ◽  
A A J O'brien ◽  
S J Armstrong ◽  
S Madhoo ◽  
C J Bulpitt ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Serum Amyloid ◽  
Amyloid P Component ◽  
Serum Amyloid P ◽  
Serum Amyloid P Component ◽  
Amyloid P

Amyloidosis

2020 ◽  
pp. 2218-2234
Author(s):  
Mark B. Pepys ◽  
Philip N. Hawkins
Keyword(s):  
Amyloid Fibrils ◽  
Amyloid Fibril ◽  
Polarized Light ◽  
Serum Amyloid ◽  
Amyloid P Component ◽  
Serum Amyloid P ◽  
Serum Amyloid P Component ◽  
Amyloid Deposits ◽  
Amyloid P

Amyloidosis is the clinical condition caused by extracellular deposition of amyloid in the tissues. Amyloid deposits are composed of amyloid fibrils, abnormal insoluble protein fibres formed by misfolding of their normally soluble precursors. About 30 different proteins can form clinically or pathologically significant amyloid fibrils in vivo as a result of either acquired or hereditary abnormalities. Small, focal, clinically silent amyloid deposits in the brain, heart, seminal vesicles, and joints are a universal accompaniment of ageing. Clinically important amyloid deposits usually accumulate progressively, disrupting the structure and function of affected tissues and lead inexorably to organ failure and death. There is no licensed treatment which can specifically clear amyloid deposits, but intervention which reduces the availability of the amyloid fibril precursor proteins can arrest amyloid accumulation and may lead to amyloid regression with clinical benefit. Pathology—amyloid fibrils bind Congo red dye producing pathognomonic green birefringence when viewed in high-intensity cross-polarized light, and the protein type can be identified by immunostaining or proteomic analysis. Amyloid deposits always contain a nonfibrillar plasma glycoprotein, serum amyloid P component, the universal presence of which is the basis for use of radioisotope-labelled serum amyloid P component as a diagnostic tracer. Clinicopathological correlation—amyloid may be deposited in any tissue of the body, including blood vessels walls and connective tissue matrix; clinical manifestations are correspondingly diverse. Identification of the amyloid fibril protein is always essential for appropriate clinical management. The specific types of amyloidosis covered in this chapter are reactive systemic (AA) amyloidosis, monoclonal immunoglobulin light chain (AL) amyloidosis, and hereditary systemic amyloidoses (including familial amyloid polyneuropathy).

scholarly journals Serum Amyloid P Component (SAP)-Like Protein From Botryllid Ascidians Provides a Clue to Amyloid Function

1992 ◽  
Vol 3 (1) ◽  
pp. 67-84 ◽  
Author(s):  
V. L. Scofield ◽  
L. Puntambekar ◽  
S. F. Schluter ◽  
D. R. Coombe
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Serum Amyloid ◽  
Amyloid Protein ◽  
Inflammatory Lesions ◽  
Serum Amyloid P ◽  
Serum Amyloid P Component ◽  
Amyloid Deposits ◽  
Fouling Organisms ◽  
Amyloid P

The HA-1 lectin isolated from Botrylloides leachii has an amino acid composition similar to that of mammalian serum amyloid protein (SAP). SAP is a universal component of mammalian amyloid deposits. Like SAP, HA-1 has a disc ultrastructure, and antibody to HA-1 binds both (a) to amyloidlike fibers deposited between rejectedBotrylloidescolonies and (b) to cerebral amyloid deposits in Alzheimer's disease brains. Deposition of protochordate amyloid within rejection sites and surrounding fouling organisms implies that these fibers function as barriers to allogeneic and infectious challenge. Similarly, mammalian amyloid may also function to contain inflammatory lesions and to limit the spread of certain infections. Pathological amyloidotic conditions in humans, such as Alzheimer's disease, may result from unregulated expression of this primitive encapsulation response.

Sign in / Sign up

Export Citation Format

Share Document