Research Projects

Using new DNA technology to reveal the role of genes in neurodegenerative diseases

Awarded to:
Prof Henry Houlden

Current award:

University College London

1 October 2023 - 30 September 2027

Full project name:

Detailed genomic and transcriptomic investigation of the MAPT locus in dementia






Tau is a protein that normally helps stabilise the structure of nerve cells in the brain. It can become abnormally folded and form clumps, called tangles, inside the nerve cells in the brain. This can lead to diseases such as Alzheimer’s disease (AD) and frontotemporal dementia (FTD).

AD is the most common cause of dementia, affecting 1 in 14 people over the age of 65, approximately 850,000 people in the UK. It causes progressive memory loss, confusion, mood changes and difficulty with daily tasks. FTD is a rarer type of dementia, accounting for under 1 in 20 of all dementia cases in the UK, however it still equates to roughly 16,000 people. FTD typically affects younger people (between 45 and 64) and causes similar symptoms to AD.

The MAPT gene provides instructions for making the tau protein, and mutations in this gene have been linked to AD and FTD. Some forms of MAPT may increase the risk of developing tau tangles, which cause nerve cell death leading to damage to the brain and the development of neurodegenerative diseases. However, researchers still do not know the mechanisms behind this.

Researchers can decipher the genetic code in our DNA using ‘sequencing’ methods, which provides clues as to how mutations in certain genes can cause disease. However, the sequencing techniques available up until now are not able to analyse the complex genetic data needed to explain how changes in the MAPT gene could lead to AD or FTD. This has led to gaps in knowledge regarding the link between tau and neurodegenerative diseases.

 Prof Houlden and his team are looking to close the gap of our knowledge. Leading to an important understanding of the mechanisms involved and how some genetic changes contribute to certain neurodegenerative diseases.


What will they do?

Prof Houlden and his team have been developing new technology over the last three years that can read longer segments of a gene and its resulting proteins. They aim to map out the DNA in and around the MAPT gene. They will use tissue samples from Queen Square Brain Bank and other brain banks, people with and without neurodegenerative diseases have donated their brains after their death.

These tissue samples will include a range of neurodegenerative disorders; AD, FTD, corticobasal degeneration (CBD; a rare progressive neurological disorder characterised by the deterioration of specific areas of the brain) and progressive supranuclear palsy (PSP; a rare neurological condition that can cause problems with balance, movement, vision, speech and swallowing).

From this they will determine whether cells with mutations in the MAPT gene change the likelihood of having faulty tau proteins building up. The team will update add their data to gene databases, such as the 100,000 Genomes Project, so they can improve the accuracy of identifying disease causing forms of the MAPT gene.


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