Fig. 7: Elevated Epinephrine (EPI) levels in AD, CBD and PS19 transgenic mice samples increases Tauopathy in OTSC through alpha-1 adrenergic signaling.
A Quantification of epinephrine (EPI) levels in the Pre-frontal (PF) cortex of AD patients from Braak stage 0-2 (n = 19) and Braak stage 6 (n = 21). P-value was calculated using Unpaired two-tailed T-test with Welch’s correction, t = 3.748, df = 28.57. B Quantification of EPI levels in the hippocampus/Entorhinal (HC/EC) cortex of AD patients from Braak stage 0-2 (n = 20) and Braak stage 6 (n = 18). P-value was calculated using Unpaired two-tailed t-test with Welch’s correction, t = 3.726, df = 24.85. C Quantification of EPI levels in the CSF of AD patients from Braak stage 0-2 (n = 6) and Braak stage 6 (n = 16). P-value was calculated using Unpaired two-tailed t-test with Welch’s correction, t = 3.764, df = 15.17. D Quantification of EPI levels in the PF cortex of CBD patients from Braak stage 0 (n = 8) and Braak stage 3 (n = 10) stages. P-value was calculated using Unpaired two-tailed t-test with Welch’s correction, t = 4.622, df = 12.17. E Quantification of EPI levels in the cortex of 9-months old mice WT (n = 6), PS19 (n = 8), CgA-KO (n = 6), and CgA-KO/PS19 (n = 7). P-value was calculated using One-way Anova (F3, 23 = 1.545, P = 0.2298) Dunnett’s multiple comparison test. F WB showing p-Tau, total tau and actin (loading control) in hippocampus OTSC lysates upon EPI treatment. G Quantification of WB of Tau phosphorylation at S202 relative to total Tau (n = 3). P-value was calculated using Unpaired two-tailed t-test with Welch’s correction, t = 18.32, df = 3.944. H Quantification of WB of Tau phosphorylation at S396/S404 relative to total Tau (n = 3). P-value was calculated using Unpaired two-tailed T-test with Welch’s correction, t = 5.292, df = 2.025. I Representative IF images showing MC1+ misfolded Tau species in hippocampus OTSC treated with EPI (top) or PBS control (bottom). Scale bar = 200 μm. J Image J quantification of MC1+ fraction in EPI (n = 3) and PBS (n = 3) treated hippocampus OTSC. P-value was calculated using Unpaired two-tailed t-test with Welch’s correction, t = 3.095, df = 3.938. K Schematic of the use of EPI and prazosin (PR) in OTSC to access Tau phosphorylation and neurofibrillary tangle formation (Created in BioRender84). L Representative images showing MC1 positive pathological Tau conformations in WT hippocampus OTSC treated with EPI, PBS, EPI+PR. Scale bar = 200 μm. M ImageJ quantification of MC1+ Tau conformations in OTSC (n = 4, per group). P-value was calculated using One-way Anova (F3, 12 = 9.786, P = 0.0015) Sidak’s Multiple Comparisons Test. Data are presented as mean values +/− SEM. Source data are provided as a Source Data file.
