(A) Tau strains (10 μg) were injected into the left hippocampus of young PS19 mice (n=3 per condition, see ). Mouse brains were collected 8-weeks after injection. Relevant regions are indicated on a representative mouse hippocampus (DG, dentate gyrus; mf, mossy fibers; Sub, Subiculum). HEK Morphology table indicates the inclusion patterns in various strains, grouped by text color. Color-coded squares indicate these HEK cell-associated patterns in all images (B-J).
(B) DS1 injection produces no AT8 tau pathology. Representative images of CA1 and CA3 are displayed. Scale bars represent 50 μm. See for whole hippocampal images for DS1-19.
(C) DS10 produces AT8 positive mossy fiber “dot” pathology, with limited CA1 pathology as observed previously (). See for contralateral mf pathology.
(D) DS14 seeds mossy fiber dots similar to DS10, as well as tangle-like pathology, indicating that it is a distinct strain despite its other similar features to DS10. See for contralateral mossy fiber and CA1 pathology.
(E) DS7 induces “wisps” that resemble neuropil threads, but may fall within axon terminals and the dendritic tree of pyramidal neurons.
(F) DS18 pathology includes wisps and mossy fiber dots similar to DS7 and 10 respectively, as well as “grains” that are found throughout much of the hippocampus. See for data indicating that these phenotypes spread to distant synaptically connected locations including the entorhinal cortex.
(G-J) Several strains produce different levels of tangle-like AT8 pathology in CA1 and CA3 of the hippocampus.
(G) DS2, 3, 11, and 19 induce rare AT8 pathology in pyramidal CA1 neurons. The localization of AT8 staining varies in certain cases (cell body versus axonal pathology in DS2 and 11 respectively).
(H) DS4, 8, 12, 13, 16, and 17 induce slightly stronger tangle-like pathology in CA1 of the hippocampus (“low tangles”). CA3 shows limited or no tangle pathology at this time point.
(I) DS5 and 9 produces AT8 tangle-like tau pathology that reaches CA3 of the hippocampus as well as CA1 pyramidal cells (“medium tangles”). Tangles appear relatively consolidated within the soma of neurons. See for spread of tau pathology to the contralateral hippocampus and ipsilateral EC.
(J) DS6 and 15 display the highest level of tangle-like AT8 pathology (“high tangles”). Highly consolidated pathology was observed throughout cell bodies and axons of CA1 and CA3 neurons. See for spread of tau pathology to the contralateral hippocampus and ipsilateral EC.