Driscoll I, Troncoso JC, Sojkova J, Zhou Y, Rudow G, Kraut MA, Ferrucci L, Mathis CA, Klunk WE, Resnick SM.
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.