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Previous Article | Next Article
The Journal of Neuroscience, March 15, 2003, 23(6):2086
The Binding of 2-(4'-Methylaminophenyl)Benzothiazole to Postmortem Brain Homogenates Is Dominated by the Amyloid Component
William E. Klunk1, Yanming Wang2, Guo-feng Huang2, Manik L. Debnath1, Daniel P. Holt2, Li Shao1, Ronald L. Hamilton3, Milos D. Ikonomovic4, Steven T. DeKosky4, and Chester A. Mathis2 1 Laboratory of Molecular Neuropharmacology, Department of Psychiatry, Western Psychiatric Institute and Clinic, 2 PET Facility, Department of Radiology, 3 Division of Neuropathology, Department of Pathology, and 4 Department of Neurology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213
2-(4'-Methylaminophenyl)benzothiazole (BTA-1) is an uncharged derivative of thioflavin-T that has high affinity for A
fibrils and shows very good brain entry and clearance. In this study, we asked whether BTA-1, at concentrations typical of those achieved during positron emission tomography (PET) studies, could specifically bind to amyloid deposits in the complex milieu of human brain or whether amyloid binding was overshadowed by nonspecific binding, found even in brains that did not contain amyloid deposits. We quantitatively assessed [3H]BTA-1 binding to crude homogenates of postmortem brain obtained from nine Alzheimer's disease (AD) subjects, eight controls, and six subjects with non-AD dementia. BTA-1 binding was >10-fold higher in AD brain, and the majority (94%) of the binding was specific (displaceable). High-affinity [3H]BTA-1 was observed only in AD brain gray matter and was not present in control brain gray matter, AD brain white matter, or cerebellum. The Kd of [3H]BTA-1 for binding to AD brain (5.8 ± 0.90 nM) was very similar to the Kd for binding to synthetic A
Key words: Alzheimer's disease; neuroimaging; plaques; neurofibrillary tangles; positron emission tomography; PET; thioflavin-T; benzothiazole; postmortem; binding
Copyright © 2003 Society for Neuroscience 0270-6474/03/2362086-07$05.00/0
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