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 [¹⁸F]FDDNP positron emission tomography (PET) scan results in a patient with dementia with Lewy bodies (DLB), with cortical neuropathology distribution determined postmortem in three physical dimensions in whole brain coronal sections. Analysis of total amyloid-β (Aβ) distribution in frontal cortex and posterior cingulate gyrus confirmed its statistically significant correlation with cortical [¹⁸F]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 [¹⁸F]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 [¹⁸F]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 were present at a much lower level than either Aβ or NFTs and did not significantly contribute to the in vivo signal. [¹⁸F]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.