Background: Alzheimer's disease (AD) is the most common type of dementia, typically characterized by memory loss followed by progressive cognitive decline and functional impairment. Many clinical trials of potential therapies for AD have failed, and there is currently no approved disease-modifying treatment. Biomarkers for early detection and mechanistic understanding of disease course are critical for drug development and clinical trials. Amyloid has been the focus of most biomarker research. Here, we developed a deep learning-based framework to identify informative features for AD classification using tau positron emission tomography (PET) scans. Methods: We analysed [18F]flortaucipir PET image data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. We first developed an image classifier to distinguish AD from cognitively normal (CN) older adults by training a 3D convolutional neural network (CNN)-based deep learning model on tau PET images (N=132; 66 CN and 66 AD), then applied the classifier to images from individuals with mild cognitive impairment (MCI; N=168). In addition, we applied a layer-wise relevance propagation (LRP)-based model to identify informative features and to visualize classification results. We compared these results with those from whole brain voxel-wise between-group analysis using conventional Statistical Parametric Mapping (SPM12). Results: The 3D CNN-based classification model of AD from CN yielded an average accuracy of 90.8% based on five-fold cross-validation. The LRP model identified the brain regions in tau PET images that contributed most to the AD classification from CN. The top identified regions included the hippocampus, parahippocampus, thalamus, and fusiform. The LRP results were consistent with those from the voxel-wise analysis in SPM12, showing significant focal AD associated regional tau deposition in the bilateral temporal lobes including the entorhinal cortex. The AD probability scores calculated by the classifier were correlated with brain tau deposition in the medial temporal lobe in MCI participants (r=0.43 for early MCI and r=0.49 for late MCI). Conclusion: A deep learning framework combining 3D CNN and LRP algorithms can be used with tau PET images to identify informative features for AD classification and may have application for early detection during prodromal stages of AD. ### Competing Interest Statement The authors have declared no competing interest.
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