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Comment
. 2021 Jun 15;2(6):100316.
doi: 10.1016/j.xcrm.2021.100316.

Astrocytic apoE4 and tau: Deadly combination for neurons

Paramita Chakrabarty  1 , David R Borchelt  1
Affiliations
Comment

Astrocytic apoE4 and tau: Deadly combination for neurons

Paramita Chakrabarty et al. Cell Rep Med. .

Abstract

New data from Wang and colleagues1 suggest that astrocyte-derived apoE4 drives tau-mediated neurodegeneration. This research highlights how a genetic risk factor for Alzheimer's disease is a major determinant of neurodegeneration in tau-expressing neurons by regulating non-cell-autonomous pathways.

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Figures

Figure 1
Figure 1
Immune cells regulate tauopathy in an APOE-dependent manner (A–E) Reducing astrocytic apoE (A) or completely ablating microglia (C) ameliorates tauopathy and neurodegeneration in PS19 mice with APOE4 (B). Ablating microglia increases astrocytic apoE, which is neuroprotective in these mice (C). Reducing astrocytic apoE reduces tauopathy (D and E) but does not alter neurodegeneration in PS19×APOE3 mice. Recent data from several labs suggest some form of cross-talk (indicated by black arrows) between neurons (indicated in gray) and immune cells (microglia in blue and astrocytes in green). Thus, it is likely that both astrocyte and microglia are required for tau-mediated neurodegeneration in the context of apoE.
See this image and copyright information in PMC

Comment on

References

    1. Wang C., Xiong M., Gratuze M., Bao X., Shi Y., Andhey P.S., Manis M., Schroeder C., Yin Z., Madore C. Selective removal of astrocytic APOE4 strongly protects against tau-mediated neurodegeneration and decreases synaptic phagocytosis by microglia. Neuron. 2021;109:1657–1674.e7. - PMC - PubMed
    1. Williams T., Borchelt D.R., Chakrabarty P. Therapeutic approaches targeting Apolipoprotein E function in Alzheimer’s disease. Mol. Neurodegener. 2020;15:8. - PMC - PubMed
    1. Shi Y., Yamada K., Liddelow S.A., Smith S.T., Zhao L., Luo W., Tsai R.M., Spina S., Grinberg L.T., Rojas J.C., Alzheimer’s Disease Neuroimaging Initiative ApoE4 markedly exacerbates tau-mediated neurodegeneration in a mouse model of tauopathy. Nature. 2017;549:523–527. - PMC - PubMed
    1. Shi Y., Manis M., Long J., Wang K., Sullivan P.M., Remolina Serrano J., Hoyle R., Holtzman D.M. Microglia drive APOE-dependent neurodegeneration in a tauopathy mouse model. J. Exp. Med. 2019;216:2546–2561. - PMC - PubMed
    1. Deczkowska A., Keren-Shaul H., Weiner A., Colonna M., Schwartz M., Amit I. Disease-Associated Microglia: A Universal Immune Sensor of Neurodegeneration. Cell. 2018;173:1073–1081. - PubMed