Journal
NEUROBIOLOGY OF AGING
Volume 32, Issue 2, Pages 223-234Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2009.02.011
Keywords
Alzheimer's disease; A beta; Benzothiazole; beta-Amyloid; Cerebral amyloid angiopathy; Imaging; Nonhuman primates; Pittsburgh Compound B; Senile plaques
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Funding
- University Research Committee of Emory University [RR-00165, PO1 AG026423, P50AG025688]
- Woodruff Foundation
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Aged nonhuman primates accumulate large amounts of human-sequence amyloid p (AD) in the brain, yet they do not manifest the full phenotype of Alzheimer's disease (AD). To assess the biophysical properties of Ail that might govern its pathogenic potential in humans and nonhuman primates, we incubated the benzothiazole imaging agent Pittsburgh Compound B (PIB) with cortical tissue homogenates from normal aged humans, humans with AD, and from aged squirrel monkeys, rhesus monkeys, and chimpanzees with cerebral A beta-amyloidosis. Relative to humans with AD, high-affinity PIB binding is markedly reduced in cortical extracts from aged nonhuman primates containing levels of insoluble A beta similar to those in AD. The high-affinity binding of PIB may be selective for a pathologic, human-specific conformation of multimeric A beta, and thus could be a useful experimental tool for clarifying the unique predisposition of humans to Alzheimer's disease. (C) 2009 Elsevier Inc. All rights reserved.
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