EuroTau: towing scientists to tau without tautology

What a change in situation... A few years ago, at the height of the amyloid cascade, tau biologists, (so called Tauists) were virtually invisible in Alzheimer’s disease conferences, which were occupied by amyloid biologists (so called baptists). Currently, sessions dedicated to tau and Tauopathies are increasing in several congresses on neurodegenerative diseases, including AAIC and AD/PD. Interest in tau biology is so great that a Tau consortium, set up especially to provide a forum for this area of research, has been created in the US. In Europe, tau biologists have gathered in tau-focused meetings organized in Cambridge, UK (2010, 2012), Madrid, Spain (2013) and more recently in Lille, France (2017). The microtubule-associated tau protein is not a new protein, it was discovered in 1975, and has featured in the game of neurodegenerative disorders since 1985. Tau is now the “Figura”, and the renewed interest in this protein leads one to ask “Why such interest in tau proteins and why now?”. There are many reasons for this burgeoning interest. Firstly the fact that most amyloid-centred therapies for Alzheimer’s disease (AD) and related disorders have demonstrated very modest, symptomatic efficacy, leaving an unmet medical need for new, more effective therapies. While drug development efforts in the last two decades have primarily focused on the amyloid cascade hypothesis, with disappointing results so far, tau-based strategies have, until recently, received little attention. This is despite the presence of extensive tau pathology, which is central not just to AD but is a key component of several other neurodegenerative diseases collectively called “Tauopathies”. Thus, focusing on tau as a drug target can have a profound bearing on diseasemodification for several neurodegenerative conditions facing our ageing society today. Secondly, multiple facets of tau biology, and therefore manifold potential implications for its role in Tauopathies, have emerged recently. Several laboratories world-wide made the seminal discovery that tau is the main component of the neurofibrillary tangles (NFT) found in AD patients more than thirty years ago, but since then, evidence has accumulated showing that posttranslational modifications such as acetylation, glycosylation, phosphorylation and truncation, among others [10, 14, 18] are pivotal in regulating tau functions. Thirdly, the discovery of some families with highly penetrant, dominant mutations within the tau gene causing fronto-temporal lobar degeneration [8] demonstrated that tau dysfunction, including its alternative splicing is sufficient to cause neurodegeneration and clinical dementia [1, 8, 14, 15]. Whilst it is still not clear how the mutations in the tau gene cause neurodegeneration, the overall effect of these mutations is predicted to be an increase in the rate of tau aggregation and eventually the formation of insoluble tau inclusions. As a result of this growing interest in tau biology, new hypotheses on the physiological and pathological role of tau are growing. It is no longer believed to be simply a microtubule-associated protein (MAP) [10] with recent advances in our understanding of tau’s cellular functions revealing functions beyond its classical role as a MAP. This has provided novel insights into its causative role in neurodegeneration. Such functions include neuronal polarization, axonogenesis, interactions with the plasma membrane and scaffold proteins, signal transduction, cell cycle, DNA/RNA protection, determination of dendritic spine density, and regulation of normal synaptic function [4, 11, 17]. Some of these are actively being pursued at present [12], thus broadening our range of potential therapeutic tools to treat AD and other tauopathies. Collectively, the recognition of tau as a key player in the pathobiology of human neurodegenerative diseases has driven substantial efforts to understand its biological and pathological functions. The spread of tau pathology through the brain of tauopathy patients has been the subject of recent research * Correspondence: luc.buee@inserm.fr Univ. Lille, Inserm, CHU-Lille, UMR-S 1172, LabEx DISTALZ, 59000 Lille, France Inserm U1172, Univ. Lille, Fac. Medecine, Place de Verdun, 59045 Lille cedex, France Full list of author information is available at the end of the article