Pittsburgh Compound‐B (PiB) binds amyloid β‐protein protofibrils. Issue 2 (12th December 2016)

• Record Type: Journal Article
• Authors: Yamin, Ghiam; Teplow, David B.
• Is Part Of: Journal of neurochemistry. Volume 140:Issue 2(2017)
• Page Start: 210
• Page End: 215
• Publication Date: 2016-12-12
• Subjects: amyloid β‐protein (Aβ) -- oligomers -- Pittsburgh Compound‐B (PiB) -- positron emission tomography (PET) -- protofibrils; Neurochemistry -- Periodicals; 616.8042
• DOI: 10.1111/jnc.13887
• Languages: English
• ISSNs: 0022-3042

Abstract

Abstract : 11 C‐Pittsburgh Compound‐B (PiB) PET is a valuable, non‐invasive tool for amyloid imaging in humans. PiB binds avidly to amyloid fibrils formed by the Alzheimer's disease amyloid β‐protein. We report here that PiB also binds to protofibrils and some oligomers, but with a lower avidity than to fibrils. PiB thus may be of use in studies involving protofibril and oligomer formation and visualization. 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.