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

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Abstract

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.

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Acknowledgments

This work was supported in part by the NIA Intramural Research Program of the National Institutes of Health. Dr. Troncoso was supported by a grant from the JHU ADRC (NIA AG05146) and the Alzheimer’s Association (IIRG-09-134090). We thank Andrew Crabb, MS, for image data management, Beth Nardi, MA, for study management, the staff of the PET facility, the Brain Bank, and the Autopsy Study at The Johns Hopkins University and the neuroimaging staff of the National Institute on Aging for their assistance.

Conflict of interest

GE Healthcare holds a license agreement with the University of Pittsburgh based on the PiB technology described in this article. Drs. Klunk and Mathis are co-inventors of PiB and, as such, have a financial interest in this license agreement.

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Authors and Affiliations

  1. National Institute on Aging, Baltimore, MD, USA

    Ira Driscoll, Jitka Sojkova, Luigi Ferrucci & Susan M. Resnick

  2. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Juan C. Troncoso, Gay Rudow & Olga Pletnikova

  3. Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Jitka Sojkova, Yun Zhou, Michael A. Kraut & Dean F. Wong

  4. Department of Radiology, University of Pittsburgh, Pittsburgh, PA, USA

    Chester A. Mathis

  5. Departments of Psychiatry and Neurology, University of Pittsburgh, Pittsburgh, PA, USA

    William E. Klunk

  6. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Juan C. Troncoso & Richard J. O’Brien

  7. Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA

    Christos Davatzikos

  8. Psychology Department, University of Wisconsin-Milwaukee, 224 Garland Hall; 2441 E Hartford Ave, Milwaukee, WI, 53211, USA

    Ira Driscoll

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  1. Ira Driscoll
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  2. Juan C. Troncoso
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  3. Gay Rudow
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  4. Jitka Sojkova
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  7. Michael A. Kraut
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Correspondence to Ira Driscoll.

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Driscoll, I., Troncoso, J.C., Rudow, G. et al. Correspondence between in vivo 11C-PiB-PET amyloid imaging and postmortem, region-matched assessment of plaques. Acta Neuropathol 124, 823–831 (2012). https://doi.org/10.1007/s00401-012-1025-1

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  • DOI: https://doi.org/10.1007/s00401-012-1025-1

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