title: Pittsburgh Compound-B (PiB) binds amyloid β-protein protofibrils.
abstract: The neuropathology of Alzheimer's disease (AD) includes amyloid plaque formation by the amyloid β-protein (Aβ) and intracellular paired helical filament formation by tau protein. These neuropathogenetic features correlate with disease progression and have been revealed in brains of AD patients using positron emission tomography (PET). One of the most useful positron emission tomography imaging agents has been Pittsburgh Compound-B (PiB). However, since its introduction in 2002, substantial evidence has accumulated suggesting that Aβ oligomerization and protofibril formation, rather than fibril formation per se, may be the more important pathogenetic event in AD. Detecting protofibrils and oligomeric forms of Aβ thus may be of value. We report here the results of experiments to determine whether PiB binds to oligomers or protofibrils formed by Aβ40 and Aβ42. We observed strong binding to Aβ42 fibrils, significant binding to protofibrils, and weaker binding to Aβ42 oligomers. PiB also binds Aβ40 fibrils, but its binding to Aβ40 protofibrils and oligomers is substantially lower than for that observed for Aβ42.
authors.affiliation: Department of Radiology, University of California San Diego School of Medicine, La Jolla, CA, USA.|Department of Neurology, David Geffen School of Medicine at UCLA, and Molecular Biology Institute (MBI) and Brain Research Institute (BRI), University of California, Los Angeles, CA, USA.
authors.forename: Ghiam
authors.initials: G
authors.lastname: Yamin
authors.affiliation: Department of Neurology, David Geffen School of Medicine at UCLA, and Molecular Biology Institute (MBI) and Brain Research Institute (BRI), University of California, Los Angeles, CA, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Teplow
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D000682:Amyloid / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D018450:Disease Progression; D006801:Humans; D016874:Neurofibrillary Tangles / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods; D011485:Protein Binding; D013844:Thiazoles / Q000494:pharmacology*; D016875:tau Proteins / Q000378:metabolism*
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000682:Amyloid; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D013844:Thiazoles; D016875:tau Proteins
keywords: Pittsburgh Compound-B (PiB); amyloid β-protein (Aβ); oligomers; positron emission tomography (PET); protofibrils