Postmortem 3-D brain hemisphere cortical tau and amyloid-β pathology mapping and quantification as a validation method of neuropathology imaging.

This work is aimed at correlating pre mortem [F-18]FDDNP PET scan results in a patient with dementia with Lewy bodies (DLB), with cortical neuropathology distribution determined post mortem in three physical dimensions in whole brain coronal sections. Analysis of total Aβ distribution in frontal cortex and posterior cingulate gyrus confirmed its statistically significant correlation with cortical [F-18]FDDNP PET binding values (distribution volume ratios, DVR) (p<0.001, R=0.97, R2=0.94). Neurofibrillary tangle (NFT) distribution correlated significantly with cortical [F-18]FDDNP PET DVR in the temporal lobe (p<0.001, R=0.87, R2=0.76). Linear combination of Aβ and NFT densities was highly predictive of [F-18]FDDNP-PET DVR through all analyzed regions of interest (p<0.0001, R=0.92, R2=0.85), and both densities contributed significantly to the model. Lewy bodies (LB) were present at a much lower level than either Aβ or NFTs and did not significantly contribute to the in vivo signal. [F-18]FDG PET scan results in this patient were consistent with the distinctive DLB pattern of hypometabolism. This work offers a mapping brain model applicable to all imaging probes for verification of imaging results with Aβ and/or tau neuropathology brain distribution using immunohistochemistry, fluorescence microscopy and autoradiography.