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Synaptic Localisation of Tau

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Tau Biology

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1184))

Abstract

The microtubule-associated protein tau has been identified in several intraneuronal compartments, including in association with synapses. In Alzheimer’s disease, frontotemporal dementia and related tauopathies, highly phosphorylated tau accumulates as intraneuronal protein aggregates that are likely responsible for the demise of neurons and the subsequent progressive cognitive decline. However, the molecular mechanisms underlying such tau-mediated damage in the tauopathies is not fully understood. Tauopathy induces loss of synapses, which is one of the earliest structural correlates of cognitive dysfunction and disease progression. Notably, altered post-translational modifications of tau, including increased phosphorylation and acetylation, augment the mislocalisation of tau to synapses, impair synaptic vesicle release and might influence the activity-dependent release of tau from neurons. Thus, disease-associated accumulation of modified tau at the synapse adversely affects critical neuronal processes that are linked to neuronal activity and synaptic function. These findings emphasise the importance of gaining a comprehensive understanding of the diverse roles of tau at distinct intraneuronal locations. An improved knowledge of the impact of synaptic tau under physiological and pathological conditions and how tau localisation impacts on neuronal function will provide valuable insights that may lead to the development of new therapies for the tauopathies.

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Acknowledgements

Work in the authors’ laboratories is supported by Alzheimer’s Research UK, the Alzheimer’s Society, and the Biotechnology and Biological Sciences Research Council.

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Authors and Affiliations

  1. Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK

    Diane P. Hanger, Despoina Goniotaki & Wendy Noble

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  1. Diane P. Hanger
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  2. Despoina Goniotaki
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  3. Wendy Noble
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Correspondence to Diane P. Hanger .

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Editors and Affiliations

  1. Department of Life Sciences, Gakushuin University, Tokyo, Japan

    Akihiko Takashima

  2. Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, USA

    Benjamin Wolozin

  3. University of Lille, INSERM, CHU-Lille, Alzheimer & Tauopathies, LabEx DISTALZ, Lille, France

    Luc Buee

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Hanger, D.P., Goniotaki, D., Noble, W. (2019). Synaptic Localisation of Tau. In: Takashima, A., Wolozin, B., Buee, L. (eds) Tau Biology. Advances in Experimental Medicine and Biology, vol 1184. Springer, Singapore. https://doi.org/10.1007/978-981-32-9358-8_9

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