Researchers led by Prof Karen Duff (UK DRI Centre Director at UCL) and Prof Andrew Yoo (Washington University School of Medicine) have created a new model system for studying the pathology of tau, a protein implicated in Alzheimer’s disease (AD), frontotemporal lobe dementias (FTD) and other neurodegenerative conditions, as reported in a new study published in Cell Stem Cell.
There are six distinct variants of tau protein present in adult human brains that differ in certain features, including the number of repeat regions in a section of the protein known as the ‘microtubule binding domain’ (termed 3R or 4R). 3R and 4R tau are expressed at a 1:1 ratio in a healthy adult human brain. The ratio is different in abnormal brains, such as those affected by FTD.
A challenge of studying tau pathology is finding a system that accurately reflects the ratio of tau present in human neurons, as adult mice do not express 3R tau, and induced pluripotent stem cells (iPSCs) do not express much 4R as they represent foetal stages of development rather than adult brain cells. Therefore, the team set out to develop a cellular model system that would provide a more accurate, representative model for studying the biology of tau, both in its healthy and diseased state.