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March 2007

Pittsburgh Compound B Retention and Verification of Amyloid Deposition

Arch Neurol. 2007;64(3):315-316. doi:10.1001/archneur.64.3.315

Making a definitive diagnosis of Alzheimer disease (AD), or more specifically determining whether the presence of amyloid plaques in the central nervous system may be contributing to the clinical phenotype in a patient with dementia, was previously possible only with brain biopsy or at autopsy. The recent development of amyloid imaging with compounds such as carbon 11 (11C)–labeled Pittsburgh Compound B (PiB) and positron emission tomography (PET) scanning is likely to ultimately change the way physicians diagnose and treat disorders in which the aggregation of β-amyloid (Aβ) plays a role.1 It has been shown in human tissue ex vivo that the amount of PiB binding correlates strongly with the amount of Aβ present as measured biochemically.2,3 Further, in tissue sections from human brain2 as well as in vivo in a transgenic mouse model with Aβ deposition,4 it appears that PiB binds to Aβ if it is present as true amyloid (ie, in a fibrillar β-pleated sheet conformation) in neuritic plaques and cerebral amyloid angiopathy. It does not appear to bind to diffuse nonfibrillar Aβ deposits. Imaging by PET with 11C-PiB in humans with a clinical diagnosis of AD vs age-matched controls has shown that most of the AD cases have significant PiB retention in several characteristic cortical regions and that many of the controls do not display this retention.1,5 Many but not all individuals with mild cognitive impairment display PiB retention, likely because the PiB-positive individuals have early AD.1,6,7 As predicted from clinicopathological studies,8 some cognitively normal individuals also have been shown to have substantial cortical PiB retention,6 likely because amyloid deposition begins 10 to 20 years prior to the onset of the clinical signs and symptoms associated with AD. All of these predictions, however, are based on the assumption that retained PiB detected by PET scans in humans is actually binding to fibrillar forms of Aβ in vivo. Until now, whether positive PiB retention definitely means there is amyloid deposition in the central nervous system had not been proven.

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