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How it all Started: Tau and Protein Phosphatase 2A

Issue title: Tau and Beyond for Alzheimer's Disease: A Special Issue dedicated to Dr. Inge Grundke-Iqbal

Guest editors: Alejandra Alonso and Chengxin Gong

Article type: Review Article

Authors: Liu, Changa | Götz, Jürgena; b; *

Affiliations: [a] Brain and Mind Research Institute, University of Sydney, Camperdown, NSW, Australia | [b] Centre for Ageing Dementia Research (CADR) at the Queensland Brain Institute (QBI), The University of Queensland, Brisbane, QLD, Australia

Correspondence: [*] Correspondence to: Jürgen Götz, Centre for Ageing Dementia Research (CADR), Queensland Brain Institute (QBI), The University of Queensland, Brisbane, QLD 4072, Australia. Tel.: +61 7 3346 6329; Fax: +61 7 3346 6301; E-mail: j.goetz@uq.edu.au.

Keywords: Alzheimer's disease, frontotemporal dementia, nucleus, protein phosphatase 2A, SFPQ, tau, transcription factor

DOI: 10.3233/JAD-130503

Journal: Journal of Alzheimer's Disease, vol. 37, no. 3, pp. 483-494, 2013

Accepted 25 April 2013
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Published: 24 September 2013
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Abstract

This review is dedicated to Inge Grundke-Iqbal who laid the foundations of the tau field, by isolating tau from the Alzheimer's disease (AD) brain, discovering that tau is hyperphosphorylated, and proving a critical role of protein phosphatase 2A (PP2A) and its endogenous inhibitor I2PP2A in this process. This memorial starts with a few personal notes, and then covers how subcellular fractionation helped in isolating tau. We review in detail the role of PP2A and its endogenous inhibitor in tau phosphorylation. We discuss the role that methylation and phosphorylation have in regulating PP2A activity. We add what we have contributed to understanding the role of tau and PP2A in AD using PP2A transgenic and knockout models, and conclude by addressing two underexplored areas in tau research: tau's non-canonical functions and the role distinct tau isoforms have in a physiological context.

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