Extracellular Tau and Its Potential Role in the Propagation of Tau Pathology - PubMed

Review

Extracellular Tau and Its Potential Role in the Propagation of Tau Pathology

Kaoru Yamada. Front Neurosci. 2017.

Abstract

The pathological aggregation of tau protein is a hallmark of a set of neurodegenerative diseases collectively referred to as tauopathies. Tau aggregates independently in each neuron, but this aggregation can also occur in a non-cell autonomous manner in which aggregated tau is transmitted from one cell to another. Such trans-cellular propagation is initiated by the uptake of extracellular tau, which then seeds soluble tau in the recipient cells to spread the tau pathology. Accumulating evidence has demonstrated that tau is not only present in the cytoplasm of neurons but also actively released into the extracellular space. This finding has led to the idea that extracellular tau could be a novel therapeutic target to halt the propagation of tau pathology. From this perspective, the present review article focuses on recent advances in understanding the mechanisms regulating the levels of extracellular tau and discusses the role of such mechanisms in the propagation of tau pathology.

Keywords: Alzheimer's disease; extracellular tau; propagation; tauopathies; unconventional protein secretion.

Similar articles

• Tau Secretion.

  Ruan Z, Ikezu T. Ruan Z, et al. Adv Exp Med Biol. 2019;1184:123-134. doi: 10.1007/978-981-32-9358-8_11. Adv Exp Med Biol. 2019. PMID: 32096034 Review.

• Tau secretion and propagation: Perspectives for potential preventive interventions in Alzheimer's disease and other tauopathies.

  Annadurai N, De Sanctis JB, Hajdúch M, Das V. Annadurai N, et al. Exp Neurol. 2021 Sep;343:113756. doi: 10.1016/j.expneurol.2021.113756. Epub 2021 May 12. Exp Neurol. 2021. PMID: 33989658 Review.

• The propagation mechanisms of extracellular tau in Alzheimer's disease.

  Wei Y, Liu M, Wang D. Wei Y, et al. J Neurol. 2022 Mar;269(3):1164-1181. doi: 10.1007/s00415-021-10573-y. Epub 2021 Apr 28. J Neurol. 2022. PMID: 33913022 Review.

• Mechanisms of secretion and spreading of pathological tau protein.

  Brunello CA, Merezhko M, Uronen RL, Huttunen HJ. Brunello CA, et al. Cell Mol Life Sci. 2020 May;77(9):1721-1744. doi: 10.1007/s00018-019-03349-1. Epub 2019 Oct 30. Cell Mol Life Sci. 2020. PMID: 31667556 Free PMC article. Review.

• What is the evidence that tau pathology spreads through prion-like propagation?

  Mudher A, Colin M, Dujardin S, Medina M, Dewachter I, Alavi Naini SM, Mandelkow EM, Mandelkow E, Buée L, Goedert M, Brion JP. Mudher A, et al. Acta Neuropathol Commun. 2017 Dec 19;5(1):99. doi: 10.1186/s40478-017-0488-7. Acta Neuropathol Commun. 2017. PMID: 29258615 Free PMC article. Review.

Cited by

• Aβ and Tau Interact with Metal Ions, Lipid Membranes and Peptide-Based Amyloid Inhibitors: Are These Common Features Relevant in Alzheimer's Disease?

  Di Natale G, Sabatino G, Sciacca MFM, Tosto R, Milardi D, Pappalardo G. Di Natale G, et al. Molecules. 2022 Aug 9;27(16):5066. doi: 10.3390/molecules27165066. Molecules. 2022. PMID: 36014310 Free PMC article. Review.

• Propagation of Tau via Extracellular Vesicles.

  Pérez M, Avila J, Hernández F. Pérez M, et al. Front Neurosci. 2019 Jul 2;13:698. doi: 10.3389/fnins.2019.00698. eCollection 2019. Front Neurosci. 2019. PMID: 31312118 Free PMC article. Review.

• Cofactors are essential constituents of stable and seeding-active tau fibrils.

  Fichou Y, Lin Y, Rauch JN, Vigers M, Zeng Z, Srivastava M, Keller TJ, Freed JH, Kosik KS, Han S. Fichou Y, et al. Proc Natl Acad Sci U S A. 2018 Dec 26;115(52):13234-13239. doi: 10.1073/pnas.1810058115. Epub 2018 Dec 11. Proc Natl Acad Sci U S A. 2018. PMID: 30538196 Free PMC article.

• News about Therapies of Alzheimer's Disease: Extracellular Vesicles from Stem Cells Exhibit Advantages Compared to Other Treatments.

  Meldolesi J. Meldolesi J. Biomedicines. 2022 Jan 5;10(1):105. doi: 10.3390/biomedicines10010105. Biomedicines. 2022. PMID: 35052785 Free PMC article. Review.

• Toxic Tau Oligomers Modulated by Novel Curcumin Derivatives.

  Lo Cascio F, Puangmalai N, Ellsworth A, Bucchieri F, Pace A, Palumbo Piccionello A, Kayed R. Lo Cascio F, et al. Sci Rep. 2019 Dec 12;9(1):19011. doi: 10.1038/s41598-019-55419-w. Sci Rep. 2019. PMID: 31831807 Free PMC article.

References

Publication types

LinkOut - more resources

• Full Text Sources

  • Europe PubMed Central
  • Frontiers Media SA
  • PubMed Central

• Other Literature Sources

  • scite Smart Citations