Researchers are one step nearer to finding out why abnormalities in the protein tau can lead to neuronal death in young-onset dementia.
Levels of the different types of tau become unbalanced in diseases such as frontotemporal dementia (FTD), Alzheimer’s and Parkinson's disease. In the brain there are six versions of tau, called isoforms, and the levels of each isoform are tightly controlled by the cell. The study of all six versions of tau is complex to do as they are not always all expressed.
For the first time researchers have demonstrated that stem cell derived neurons can express all six isoforms of tau, and that the levels were unsettled in cells from patients with FTD.
Lead author Dr Selina Wray, based in UCL’s Department of Molecular Neuroscience, said: “We know tau is important in diseases but it has been difficult to study in the laboratory because many cell and animal systems routinely used for disease modelling do not express all the different versions of tau.”
To overcome this difficulty the researchers took stem cells from patients with FTD linked to changes in tau processing and cells from individuals without dementia. They converted the stem cells into neurons using novel technology which allows this to be done in the laboratory where the neurons can be grown in a dish. The neurons were then analysed to see which versions of tau were present at different time points.
Dr Wray, who is supported by the NIHR Queen's Square Dementia Biomedical Research Unit, said: “We wanted to assess whether stem cell derived neurons express all six versions of tau, at the correct levels and whether it would be disrupted in cells from patients with alterations in tau processing”.
The findings, published in Human Molecular Genetics, may be a useful system to understand the biological basis of FTD and why tau abnormalities lead to neuronal death.
Researchers anticipate the study results could influence the selection of treatments for patients with diseases involving tau. Dr Wray said: “For the moment we are further characterising our model to understand the consequences of altered tau processing, in regards to clinical application, we hope in the future this model could be used for drug screening in the laboratory.”
To read Developmental regulation of tau splicing is disrupted in stem cell derived neurons from frontotemporal dementia patients with the 10+16 splice-site mutation in MAPT in full click here.
