Extended Data Fig. 4: DOPEGAL modification of Tau is regulated by AEP and MAO-A.
From: Tau modification by the norepinephrine metabolite DOPEGAL stimulates its pathology and propagation
DOPEGAL (0.25 μg) was injected into the LC regions of MAPT and MAPT/AEP-/- mice. DOPEGAL modification and cleavage of Tau in the LC were examined by immunofluorescence staining. A. Representative images of DBH (green), TauK353-DOPEGAL (red), and DAPI (blue); Tau N368 (green), TauK353-DOPEGAL (red), and DAPI (blue) staining in LC sections of DOPEGAL-injected MAPT and MAPT/AEP-/- mice. Scale bar is 100 μm. B,C. Quantification of TauK353-DOPEGAL + (B) and Tau N368 + cells (C). Data are shown as mean ± SEM. n = 6 per group. Two-way ANOVA with Sidak’s multiple comparison. D. AAV-control or AAV-MAO-A was injected into the LC regions of MAPT mice. Neuronal cell death (TUNEL) and DOPEGAL modification (Tau K353-DOPEGAL), cleavage (Tau N368), phosphorylation (AT8), and aggregation (T22) of Tau in the LC were examined by immunofluorescence staining. Scale bar is 100 μm. E. Co-stained positive cells were quantified in the LC of AAV-injected MAPT mice. Data are shown as mean ± SEM. n = 6 per group. Student t-test.
