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The extensive cortical tau tangle pathology present in 5.5 months old vehicle (veh) treated P301S mice (A) was widely attenuated in long-term rapamycin (rapa) treated mice (B).

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posted on 2013-05-07, 02:36 authored by Sefika Ozcelik, Graham Fraser, Perrine Castets, Véronique Schaeffer, Zhiva Skachokova, Karin Breu, Florence Clavaguera, Michael Sinnreich, Ludwig Kappos, Michel Goedert, Markus Tolnay, David Theo Winkler

The lowering in tangle formation was most pronounced in the motor cortex (C: left vehicle treated/right rapamycin) and associated with reduced pathological tau hyperphosphorylation at the AT8 and AT100 epitopes (D, E). In parallel, cortical astrogliosis was diminished following rapamycin treatment (F). While there was a trend towards a reduction of the sparse tangles in the hippocampus, the advanced tau pathology in the brain stem however was not significantly ameliorated by rapamycin (G, H). Short-term treatment at 3 months of age for 6 weeks again resulted in a marked reduction of cortical tangles (I) (A–H: 5MT group; I: 6WT. A–C, G–I: Gallyas silver stain; D: AT8 IHC; E: AT100 IHC; F: GFAP IHC. Bar in A equals 300 µm in A and B, 150 µm in C, G and I, 75 µm in D–F, 600 µm in H).