Frantic brain activity!
November 2006Dr Stuart Pickering-Brown of the Division of Regenerative Medicine has won a grant of around £770k over three years from the Medical Research Council (MRC), to carry out follow-on work from his recent ground-breaking paper in Nature. The study linked the gene progranulin to frontotemporal dementia (FTD) for the first time, and the team will now be able to analyse the progranulin protein and peptide molecules in the brain.
“We will investigate whether levels of and/or modifications to these correlate with the clinical features and/or distribution of pathology of frontotemporal dementia,” Stuart says. “Because all known progranulin mutations in FTD cause loss of ribonucleic acid (RNA) we will also investigate whether levels of RNA correlate with pathology, as well as looking at other brain proteins that interact with progranulin.”
The MRC has also granted Stuart a £65k supplement to start cell biological work on progranulin, the first time such an award has been made in the funding council’s history, and he is an author on four papers published in a special issue of Brain commemorating 100 since the classification of Alzheimer's disease.
“The paper I’m first author on concerns the first gene identified as causing FTD, tau,” he says. “We’d previously identified tau mutations which had a different pathology to that usually seen - a ‘tau-negative’ pathology - but thought that tau mutations must just be able to cause disease via two very different routes.
“However, when we linked the progranulin gene - also on chromosome 17 - to FTD for the Nature paper, we noticed that our patients with progranulin mutations had this same tau-negative neuropathology. So we screened all our ‘tau mutations’ cases with the tau-negative pathology, and it turned out they all actually had progranulin mutations.
“This proved that what we thought were mutations in tau were in fact just rare, benign variants, and it was the progranulin mutation which was causing FTD. It also killed the hypothesis that there are two routes to tau-related disease – there is only one, and it leads to a straightforward tau-based pathology.”
