Fig. 1

Tau pipeline overview. a In QuPath, a whole slide image is digitally separated into haematoxylin, DAB, and residual channels. Tissue segmentation for region of interest follows where grey matter is segmented from cortical slides, subthalamic nucleus, globus pallidus and putamen are segmented from basal ganglia slides, and dentate nucleus is segmented from cerebellum slides. Obvious artefacts are also manually removed. b DAB thresholding is performed to detect tau objects (in green) and features are extracted for each object. c Tau classification (examples presented in yellow and blue boxes for a pre-frontal slide) begins with separating non-tau artefacts from tau objects using a universal screening classifier and tau objects are then classified into different tau types using region-specific tau classifiers (which include 4 different tau classifiers, for cortical regions, putamen, subthalamic nucleus and globus pallidus, and dentate nucleus). Final slide checking is required to ensure accurate results before subsequent analysis. TA Tufted astrocyte, NFT Neurofibrillary tangle, CB coiled bodies, TF tau fragments, DAB 3,3′-diaminobenzidine