Pittsburgh Compound-B (PiB) binds amyloid β-protein protofibrils

The neuropathology of Alzheimer's disease (AD) includes amyloid plaque formation by the amyloid beta-protein (A beta) 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 A beta 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 A beta thus may be of value. We report here the results of experiments to determine whether PiB binds to oligomers or protofibrils formed by A beta 40 and A beta 42. We observed strong binding to A beta 42 fibrils, significant binding to protofibrils, and weaker binding to A beta 42 oligomers. PiB also binds A beta 40 fibrils, but its binding to A beta 40 protofibrils and oligomers is substantially lower than for that observed for A beta 42.