Striatal amyloid plaque density predicts braak neurofibrillary tangle stage and clinicopathological Ad: Implications for amyloid imaging

Amyloid imaging may revolutionize Alzheimer's disease (AD) research and clinical practice but is critically limited by the lack of correlation between cerebral cortex amyloid plaques and dementia. Also, amyloid imaging does not indicate the extent of neurofibrillary tangle spread throughout the brain. Autopsy studies suggest that striatal amyloid plaques correlate with dementia and Braak neurofibrillary tangle (NFT) stage. Striatal amyloid plaques, readily identified by amyloid imaging, might be used to predict, in living subjects, NFT stage and the likelihood that dementia is due to AD. The sensitivity and specificity of striatal plaque density scores, assigned on a 0-3 semi-quantitative scale using Campbell-Switzer and thioflavine S stains, for indicating Braak neurofibrillary tangle (NFT) stage and the presence of clinicopathological AD (dementia, NIA-Reagan “intermediate”) was determined in a postmortem series of 165 elderly subjects. Subjects were clinicopathologically classified as 26 non-demented elderly controls, 124 with AD, 18 with dementia with Lewy bodies, 18 with vascular dementia and 7 with hippocampal sclerosis dementia (some with more than one diagnosis). Subjects that had presented with movement disorders, including Parkinson's disease, progressive supranuclear palsy and corticobasal degeneration were excluded. higher striatal plaque density score (3 or 2-3) predicted a higher Braak NFT stage (Braak V and VI or Braak IV-VI) with sensitivities ranging from 73% to 96% and specificities ranging from 62% to 89%. The best combined diagnostic performance (sensitivity 81%, specificity 84%) was for a striatal plaque score of 2 or 3 predicting Braak NFT stages of IV, V or VI. A higher striatal plaque density score predicted the presence of dementia and clinicopathological AD with sensitivities ranging from 56% to 86% and specificities ranging from 76% to 92%. The best performance (sensitivity 86%, specificity 76%) was for a striatal plaque score of 2 or 3 predicting dementia with clinicopathological AD. Amyloid imaging of the striatum may be useful as a predictor, in living subjects, of Braak NFT stage and the presence or absence of dementia and clinicopathological AD. Validation of this hypothesis will require autopsy studies of subjects that had amyloid imaging during life.