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The propagation mechanisms of extracellular tau in Alzheimer’s disease

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Abstract

Tubulin-associated unit (tau) is an important microtubule-associated protein. The abnormal intracellular aggregation of tau has been strongly associated with Alzheimer's disease (AD). Accumulating evidence has conclusively demonstrated that tau is present in the cytoplasm of neurons and is also actively released into the extracellular space. However, the types of tau species that are released are unclear, as is the mechanism of their release by donor neurons and subsequent uptake by recipient neurons in AD. Understanding the underlying mechanisms of abnormal tau cell-to-cell transmission can provide novel insights into the etiology and pathogenesis of AD and can help identify new targets for the development of AD therapies focused on counteracting neurodegeneration or even preventing it. From this perspective, the present review 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-associated pathology.

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Abbreviations

AD:

Alzheimer's disease

CSF:

Cerebrospinal fluid

EV:

Extracellular vesicle

MT:

Microtubule

NFT:

Neurofibrillary tangle

PHF:

Paired helical filaments

PM:

Plasma membrane

PTM:

Post-translational modification

Tau:

Tubulin-associated unit

TNTs:

Tunneling nanotubes

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Funding

The authors gratefully acknowledge the financial support provided by the Beijing Science and Technology Planning Project (grant number No. Z171100001017106) and the National Natural Science Foundation of China (No. 81904194).

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  1. Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing city, 100091, China

    Yun Wei & Meixia Liu

  2. Jining Hospital of Integrated Traditional Chinese Medicine and Western Medicine, Shandong province, 272000, China

    Dongxin Wang

Authors
  1. Yun Wei
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  2. Meixia Liu
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  3. Dongxin Wang
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Contributions

As the co-first author, Yun Wei and Meixia Liu wrote the manuscript. Dongxin Wang helped with initial writing. Yun Wei edited and revised the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Yun Wei.

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The authors declare that they have no competing interests.

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This article is a review and does not involve human or animal specimens.

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Wei, Y., Liu, M. & Wang, D. The propagation mechanisms of extracellular tau in Alzheimer’s disease. J Neurol 269, 1164–1181 (2022). https://doi.org/10.1007/s00415-021-10573-y

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  • DOI: https://doi.org/10.1007/s00415-021-10573-y

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