The pathway linking the tau and amyloid precursor proteins in neurodegeneration
Lithium is first-line therapy for bipolar disorder, but has many side effects that limit its use. One side effect is parkinsonism. Understanding the molecular mechanism of lithium-induced parkinsonism is of importance for bipolar disease, but will also contribute to our understanding of Parkinson’s disease. He has previously found that a protein called ‘tau’ is reduced in the brains of Parkinson’s disease patients, and reducing tau in mice recapitulated a number of key symptoms of Parkinson’s disease. He has been able to demonstrate that tau reduction caused iron accumulation in mouse brain, which manifested symptoms of Parkinson’s disease. In this project, we showed that lithium treatment to cells caused tau-mediated iron accumulation, and lithium treatment to normal mice (at the therapeutic dose) caused parkinsonism via tau mediated pathway. He further analysed brain-iron content (by MRI) in a group of healthy volunteers before and after they took lithium, and found iron elevation in a region of the brain associated with Parkinson’s disease. These results are in accordance with his previous findings that collectively support the direct involvement of tau protein in Parkinson’s disease in addition to its unique role in Alzheimer’s disease.
Dr Lei was awarded a prestigous NHMRC Early Career Fellowship in mid 2013 and subsequently recinded his AADRF fellowship in August 2013.