Fig. 1

Injection of proteopathic tau seeds in the mouse brain induces somatodendritic tau pathology locally and in distant regions that project axons to the injected area. A, B Schematic diagrams showing neurons with their projection in the known neural circuit and the regions with induced tau pathology after tau inoculation. Projection axons and their terminals are shown as bold lines and bifurcations, respectively. Neurons exhibiting somatodendritic tau pathology and axonal tau accumulation are shown in red (the brain region/subregion in pink), and those free from somatodendritic tau burden in green. After injection of tau seeds into the hippocampus, layers II (L_II) and III (L_III) of the entorhinal cortex (EC) showed somatodendritic tau inclusions, whereas the EC deep layers (DL) only show axonal tau accumulation (A); the distinct patterns clearly demarcated the superficial layers from deep layers of the EC [9]. Tau pathology was induced in the locus coeruleus after tau inoculation in the hippocampus, but not vice versa (B) [14]. C Schematic diagram showing proposed model of induced tau pathology in the mouse brain after tau inoculation. Somatodendritic tau pathology is seen mostly in the injection area and type I distant brain regions in which neurons project axons to the injected region. Note that this category includes distant regions that are bidirectionally connected to the injected area. However, the type II distant region, where neurons receive axonal inputs from but do not project axons to the injected area, exhibits only axonal/neuritic tau pathology without somatodendritic tau burden