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

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 11C-Pittsburgh compound-B (PiB)-PET ligand remains the most widely studied to date; however, regional variations in 11C-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 11C-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 11C-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 11C-PiB-PET imaging as a method for evaluation of plaque burden in vivo.