Post-mortem correlates of in vivo PiB-PETamyloid imaging in a typical case of Alzheimer’s disease

The positron emission tomography (PET) radiotracer Pittsburgh Compound-B (PiB) binds with high affinity to b-pleated sheet aggregates of the amyloid-b (Ab) peptide in vitro.The in vivo retention of PiB in brains of people with Alzheimer’s disease shows a regional distribution that is very similar to distribution of Ab deposits observed post-mortem. However, the basis for regional variations in PiB binding in vivo, and the extent to which it binds to different types of Ab-containing plaques and tau-containing neurofibrillary tangles (NFT), has not been thoroughly investigated. The present study examined 28 clinically diagnosed and autopsy-confirmed Alzheimer’s disease subjects, including one Alzheimer’s disease subject who had undergone PiB-PET imaging 10 months prior to death, to evaluate region- and substrate-specific binding of the highly fluores-cent PiB derivative 6-CN-PiB.These datawere then correlatedwith region-matched Ab plaque load and peptide levels, [3H]PiB binding in vitro, and in vivo PETretention levels.We found that in Alzheimer’s disease brain tissue sections, the preponderance of 6-CN-PiB binding is in plaques immunoreactive to either Ab42 or Ab40, and to vascular Ab deposits. 6-CN-PiB labelling was most robust in compact/cored plaques in the prefrontal and tem-poral cortices.While diffuse plaques, including those in caudate nucleus and presubiculum, were less prominently labelled, amorphous Ab plaques in the cerebellum were not detectable with 6-CN-PiB.Only a small subset of NFTwere 6-CN-PiB positive; these resembled extracellular ‘ghost ’ NFT. In Alzheimer’s disease brain tissu