Prospects for noninvasive imaging of brain amyloid beta in Alzheimer's disease.
The brain in patients with Alzheimer's disease (AD) contains large amounts of fibrillary amyloid beta protein. Studies attempting to use levels of amyloid beta protein in plasma, cerebrospinal fluid or skin as diagnostic tests for the disease have not been fruitful. A method for the noninvasive detection of cerebral amyloid beta would be valuable for dementia differential diagnosis, pathophysiology and monitoring of anti-amyloid therapies. Anti-amyloid monoclonal antibody 10H3 has been evaluated as an amyloid-imaging ligand, without success. Important considerations in the development of amyloid-imaging ligands include choice of radiolabel and physical and biological half-lives, route of administration, protein binding, use of control molecules, and imaging techniques. It is important that imaging studies be designed to reflect the slow nature of the process of amyloid deposition. We used a transgenic mouse model overexpressing beta protein precursor (beta PP) to assess the binding of basic fibroblast growth factor (bFGF) and serum amyloid P component (SAP) to amyloid beta (A beta) plaques in mouse brain. Although the binding of these ligands is similar to AD, neither is found endogenously associated with A beta deposits. Because SAP is a component of mouse serum, these findings suggest the blood-brain barrier in transgenic mice is not affected as it is in AD. These findings suggest that the transgenic mouse may be used as a model for evaluation of A beta imaging methods.
Friedland
R P
RP
Department of Neurology, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA. rpf2@po.cwru.edu
Shi
J
J
Lamanna
J C
JC
Smith
M A
MA
Perry
G
G
D000544:Alzheimer Disease / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000032:analysis* / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D000911:Antibodies, Monoclonal; D001812:Blood-Brain Barrier; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology*; D016222:Fibroblast Growth Factor 2 / Q000032:analysis* / Q000378:metabolism; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D058225:Plaque, Amyloid / Q000473:pathology; D000683:Serum Amyloid P-Component / Q000032:analysis* / Q000378:metabolism; D013667:Technetium; D015899:Tomography, Emission-Computed, Single-Photon
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000911:Antibodies, Monoclonal; D000683:Serum Amyloid P-Component; D016222:Fibroblast Growth Factor 2; D013667:Technetium