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On the causal role of retromer-dependent endosomal recycling in Alzheimer’s disease

Nature Cell Biology volume 25, pages 1394–1397 (2023)Cite this article

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Recent findings ranging from genetics to structural biology, together with studies in human neurons, animal models and patient brains, implicate the retromer-dependent endosomal recycling pathway as both causal and common in Alzheimer’s disease.

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Fig. 1: Retromer-dependent endosomal recycling and the integrative biology of AD.

References

  1. Petsko, G. A. & Small, S. A. Science 377, 31–32 (2022).

    Article  CAS  PubMed  Google Scholar 

  2. Small, S. A. & Gandy, S. Neuron 52, 15–31 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Rogaeva, E. et al. Nat. Genet. 39, 168–177 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Holstege, H. et al. Nat. Genet. 54, 1786–1794 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Scheltens, P. et al. Lancet 397, 1577–1590 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Kovtun, O. et al. Nature 561, 561–564 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Jensen, A. M. G. et al. Proc. Natl Acad. Sci. USA 120, e2212180120 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Mishra, S. et al. Cell Mol. Life Sci. 79, 162 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Simoes, S. et al. Cell Rep. 37, 110182 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Qureshi, Y. H. et al. Cell Rep. 38, 110262 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Knupp, A. et al. Cell Rep. 31, 107719 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Asadzadeh, J. et al. Nat. Commun. 13, 5049 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Simoes, S. et al. Sci. Transl. Med. 12, eaba6334 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Vaz-Silva, J. et al. EMBO J. 37, e99084 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  15. Andersen, O. M. et al. Cell Rep. Med. 3, 100740 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Daly, J. L. et al. Nat. Commun. 14, 3086 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Bota, M., Sporns, O. & Swanson, L. W. Proc. Natl Acad. Sci. USA 112, E2093–E2101 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Small, S. A. & Swanson, L. W. Cold Spring Harb. Symp. Quant. Biol. 83, 193–200 (2018).

    Article  PubMed  Google Scholar 

  19. Gouras, G. K., Tampellini, D., Takahashi, R. H. & Capetillo-Zarate, E. Acta Neuropathol. 119, 523–541 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Kwart, D. et al. Neuron 104, 256–270.e5 (2019).

    Article  CAS  PubMed  Google Scholar 

  21. Chen, X. Q. et al. Ann. Neurol. 594, 245–258 (2023).

    Article  Google Scholar 

  22. Vardarajan, B. N. et al. Neurobiol. Aging 33, 2231.e2215–2230 (2012).

    Article  Google Scholar 

  23. Morabito, M. V. et al. Neurobiol. Dis. 65, 188–192 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Sims, J. R. et al. JAMA 330, 512–527 (2023).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA

    Jessica E. Young

  2. Genomics of Neurodegenerative Diseases and Aging, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands

    Henne Holstege

  3. Danish Research Institute of Translational Neuroscience (DANDRITE), Department of Biomedicine, Aarhus University, Aarhus, Denmark

    Olav M. Andersen

  4. Department of Neurology and the Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham & Women’s Hospital, Boston, MA, USA

    Gregory A. Petsko

  5. Department of Neurology, Columbia University, New York, NY, USA

    Scott A. Small

  6. The Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University, New York, NY, USA

    Scott A. Small

Authors
  1. Jessica E. Young
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  2. Henne Holstege
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  3. Olav M. Andersen
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  4. Gregory A. Petsko
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  5. Scott A. Small
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Corresponding author

Correspondence to Scott A. Small.

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Competing interests

G.A.P., S.A.S. and O.M.A. own equity in and are paid consultants for Retromer Therapeutics, Inc. J.E.Y. has a sponsored research agreement with Retromer Therapeutics, inc. H.H. is a paid consultant for Retromer Therapeutics Inc.

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Nature Cell Biology thanks Gunnar Gouras, Matthew Seaman, and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Young, J.E., Holstege, H., Andersen, O.M. et al. On the causal role of retromer-dependent endosomal recycling in Alzheimer’s disease. Nat Cell Biol 25, 1394–1397 (2023). https://doi.org/10.1038/s41556-023-01245-2

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