Using C. elegans to understand seeding and spreading of tau aggregation

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Alzheimer's disease (AD) is a common and devastating neurodegenerative disorder, and there are currently no effective treatments for it. The underlying cause of AD is believed to be the "clumping" together of proteins called ABeta and tau into large structures called aggregates. These clumps, once formed, may then spread into different cells of the brain. We aim to discover how clumps of tau form and spread between cells, and how we might be able to prevent this from happening. First of all, we will find out whether other proteins that normally clump together when cells get older might cause the formation of tau aggregates that lead to disease. Next, we will genetically manipulate a microscopic worm called Caenorhabditis elegans (C. elegans) to produce tau in different cells, giving us a better way to investigate how tau clumps together and spreads between cells, as C. elegans are easy to genetically modify. We will then change the expression of different genes in C. elegans, to see whether this affects the progress of tau clumping and spreading. In particular, we will change the levels of the proteins that normally form aggregates with age, to see how this affects tau; and we will investigate a pathway called the unfolded protein response (UPR) that is also able to spread between cells, to see if this affects the spreading of tau. If we find ways to influence the formation and spreading of tau aggregates, these genes and the molecular pathways may make promising targets for the development of new drugs against AD, a hugely important goal that could ultimately improve the lives of thousands of AD sufferers and their carers.