. Correspondence between in vivo PiB-PET amyloid imaging and post-mortem, regional burden of As and Tau lesions. Human Amyloid Imaging 2011 Meeting Abstracts. 2011 Jan 15;


The definitive diagnosis of AD requires post-mortem confirmation of neuropathological hallmarks . amyloid-s plaques (As) and neurofibrillary tangles. The advent of radiotracers for amyloid imaging presents an opportunity to investigate amyloid deposition in vivo. The Pittsburgh Compound-B (PiB) PET ligand remains the most widely studied to date; however, the extent of agreement with neuropathological assessment has not been thoroughly investigated. We examined the correspondence among quantitative immunohistological assessments of As and phosphorylated Tau in post-mortem tissues, and regional PiB load (PET) and brain volume (MRI) in 6 older Baltimore Longitudinal Study of Aging participants who came to autopsy. Based on consensus clinical diagnosis, five were nondemented and one demented. All individuals underwent PiB-PET and MRI assessments with imaging-autopsy intervals ranging between 1.1 to 2.4 years. We used unbiased stereology (fractional area) to estimate the burden of As (6E10) and Tau (PHF1) immunoreactivities in 5 random, systematically-selected paraffin sections from each of the following regions: hippocampus, orbito-frontal cortex, anterior and posterior cingulate gyri, precuneus and cerebellum. The cerebellum served as a reference region for in vivo quantification of As and was negative for both As and Tau immunoreactivity. In general, there was agreement between the regional measures of As obtained stereologically and via imaging, with significant associations observed for 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 significant associations were observed between PiB load and Tau immunoreactivity (pfs>0.2). Moreover, neither As or Tau immunoreactivity were associated with regional brain volumes (pfs>0.05). Methodological differences notwithstanding, we report an agreement between amyloid imaging and post-mortem assessment of As deposition. The strong correlation of in vivo PiB retention with region-matched, quantitative analyses of As in post-mortem tissue offers support for the validity of PiB-PET imaging as a method for evaluation of As burden in vivo.


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  1. Miami: HAI Amyloid Imaging Conference Abstracts