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. 2021 Sep 2;11:17604. doi: 10.1038/s41598-021-97117-6

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Schematic diagram of the relationship between ApoE4 and FoxO3a in AD pathogenesis. ApoE4 represses the transcription factor FoxO3a. Downregulation of FoxO3a reduces the protein levels of its autophagy/mitophagy-related downstream genes, such as Atg12, Beclin-1, BNIP3, and PINK1, which could result in an impairment of autophagy and mitophagy. Dysfunction of autophagy might increase the levels of phosphorylated tau proteins, leading to AD pathogenesis.