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. 7. Schematic model for the pathological role of ApoE4 through inhibiting VMAT2 in LC neurodegeneration.

Fig. 7.

Our data support a model in which ApoE4 blocks VMAT2 and elevates DOPEGAL concentrations in the cytoplasm via NE leakage, which in turn activates AEP, exacerbates Tau toxicity, and prompts LC neurodegeneration. In contrast, ApoE3 binds to Tau and prevents Tau N368 cleavage by AEP.