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Prospects for Noninvasive Imaging of Brain Amyloid β in Alzheimer's Disease
Author(s) -
FRIEDLAND R. P.,
SHI J.,
LAMANNA J. C.,
SMITH M. A.,
PERRY G.
Publication year - 2000
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2000.tb06358.x
Subject(s) - genetically modified mouse , amyloid (mycology) , amyloid beta , serum amyloid p component , alzheimer's disease , beta (programming language) , dementia , amyloid precursor protein , transgene , cerebrospinal fluid , pathology , chemistry , medicine , disease , biochemistry , inflammation , c reactive protein , computer science , gene , programming language
A bstract : The brain in patients with Alzheimer's disease (AD) contains large amounts of fibrillary amyloid β protein. Studies attempting to use levels of amyloid β 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 β 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 β protein precursor (βPP) to assess the binding of basic fibroblast growth factor (bFGF) and serum amyloid P compo nent (SAP) to amyloid β (Aβ) plaques in mouse brain. Although the binding of these ligands is similar to AD, neither is found endogenously associated with Aβ 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 Aβ imaging methods.