Correspondence between in vivo (11)C-PiB-PET amyloid imaging and postmortem, region-matched assessment of plaques

• Published in: Acta neuropathologica Vol. 124; no. 6; pp. 823 - 831
• Main Authors: Driscoll, Ira, Troncoso, Juan C, Rudow, Gay, Sojkova, Jitka, Pletnikova, Olga, Zhou, Yun, Kraut, Michael A, Ferrucci, Luigi, Mathis, Chester A, Klunk, William E, O'Brien, Richard J, Davatzikos, Christos, Wong, Dean F, Resnick, Susan M
• Format: Journal Article
• Language: English
• Published: Germany Springer 01.12.2012
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - diagnostic imaging; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Amyloid beta-Peptides - metabolism; Aniline Compounds; Autopsy - methods; Benzothiazoles - metabolism; Brain; Diagnosis; Diagnostic imaging; Female; Humans; Male; Neurofibrillary Tangles - diagnostic imaging; Neurofibrillary Tangles - metabolism; Neurofibrillary Tangles - pathology; Neuroimaging - methods; Plaque, Amyloid - diagnostic imaging; Plaque, Amyloid - metabolism; Plaque, Amyloid - pathology; Positron-Emission Tomography; Thiazoles
• ISSN: 0001-6322; 1432-0533
• DOI: 10.1007/s00401-012-1025-1

The definitive Alzheimer's disease (AD) diagnosis requires postmortem confirmation of neuropathological hallmarks-amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs). The advent of radiotracers for amyloid imaging presents an opportunity to investigate amyloid deposition in vivo. The (11)C-Pittsburgh compound-B (PiB)-PET ligand remains the most widely studied to date; however, regional variations in (11)C-PiB binding and the extent of agreement with neuropathological assessment have not been thoroughly investigated. Sojkova and colleagues [35] reported variable agreement between CERAD-based neuropathologic diagnosis of AD lesions and mean cortical PiB, suggesting the need for a more direct quantification of regional Aβ in relation to in vivo imaging. In the present study, we extend these findings by examining the correspondence among regional (11)C-PiB load, region-matched quantitative immunohistological assessments of Aβ and NFTs, and brain atrophy (MRI) in six older Baltimore Longitudinal Study of Aging participants who came to autopsy (imaging-autopsy interval range 0.2-2.4 years). The total number of Aβ plaques (6E10) and NFTs (PHF1) in paraffin sections from hippocampus, orbito-frontal cortex, anterior and posterior cingulate gyrus, precuneus and cerebellum was quantified using a technique guided by unbiased stereological principles. We report a general agreement between the regional measures of amyloid obtained via stereological assessment and imaging, with significant relationships evident for the anterior (r = 0.83; p = 0.04) and posterior (r = 0.94; p = 0.005) cingulate gyri, and the precuneus (r = 0.94; p = 0.005). No associations were observed between (11)C-PiB load and NFT count for any of the regions examined (p > 0.2 in all regions), or between regional Aβ or NFT counts and corresponding brain volumes. The strong associations of PiB retention with region-matched, quantitative analyses of Aβ in postmortem tissue offer support for the validity of (11)C-PiB-PET imaging as a method for evaluation of plaque burden in vivo.