Skip to main content
. Author manuscript; available in PMC: 2022 Jul 1.
Published in final edited form as: Acta Neuropathol. 2021 Apr 25;142(1):139–158. doi: 10.1007/s00401-021-02315-1

Fig. 3. ApoE4-elicited neurotoxicity is dependent on AEP cleavage of Tau N368.

Fig. 3.

Primary neurons were cultured and infected with AAV-hTau, AAV-ApoE3 or ApoE4, and AAV-AEP or AEP C189S. a. Western blot analysis showed that ApoE4 overexpression induced Tau phosphorylation and Tau N368 cleavage with AEP overexpression but not inactive AEP C189S. b. LDH assay showed that ApoE4 or AEP overexpression in neurons induced cell death. c. The activation of AEP was confirmed by enzymatic assay. Data are shown as mean ± SEM. N=3 per group. * p<0.05. Primary neurons were infected with AAV-hTau and AAV-ApoE3/E4, followed by treatment with vehicle or the AEP inhibitor, compound 11(10 μM). d. Western blot analysis showed that Tau and ApoE4-induced AEP activation, Tau phosphorylation, and Tau N368 cleavage were blocked by compound 11. e. LDH assay showed that cell death by Tau and ApoE4 was inhibited by compound 11. f. The inhibition of AEP was confirmed by enzymatic assay. Data are shown as mean ± SEM. N=3 per group. * p<0.05. Primary neurons were infected with AAV-ApoE3/E4 and AAV-Tau/Tau N255A/N368A. g. Western blot analysis showed that non-cleavable Tau N255A/N368A repressed the effects of Tau and ApoE4 in AEP activation, Tau phosphorylation, and Tau N368 cleavage, h. LDH assay indicating the blocking effect of Tau N225A/N368A in cell death by Tau and ApoE4. i. The activation of AEP was confirmed by enzymatic assay. Data are shown as mean ± SEM. N=3 per group. * p<0.05, ** p<0.01.