AUTHOR=Wray Selina , Lewis Patrick A.

TITLE=A Tangled Web – Tau and Sporadic Parkinson's Disease

JOURNAL=Frontiers in Psychiatry

VOLUME=Volume 1 - 2010

YEAR=2010

URL=https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2010.00150

DOI=10.3389/fpsyt.2010.00150

ISSN=1664-0640

ABSTRACT=Parkinson's disease (PD) represents a major challenge for health care systems around the world: it is the most common degenerative movement disorder of old age, affecting over 100,000 people in the UK alone. A great deal of progress has been made in understanding the molecular basis of PD by taking advantage of advances in genetics, initially by the identification of genes responsible for rare mendellian forms of PD (outlined in table one), and more recently by applying genome wide association studies (GWAS) to the sporadic form of the disease. Several such GWAS have now been carried out, with a meta-analysis currently under way. Using over 6000 cases and 10000 controls, two of these studies have identified variation at a number of loci as being associated with an increased risk of disease.  Three genes stand out as candidates from these studies – the SNCA gene, coding for α -synuclein, the LRRK2 gene, coding for leucine rich repeat kinase 2, and MAPT, coding for the microtubule associated protein tau.  Point mutations in α -synuclein, along with gene multiplication events, result in autosomal dominant PD, often with a significant dementia component. In addition to this, α -synuclein is the principle component of the main pathological hallmark of PD, the Lewy body. Mutations in LRRK2 are the most common genetic cause of PD, and so again were a likely candidate for a susceptibility locus for the sporadic form of disease. More surprising, perhaps, was the identification of tau as a susceptibility factor for Parkinson's.  In this review we will outline the role of tau in neurodegeneration and in different forms of parkinsonism, and speculate as to what the functional basis of this association might be.