£2 million study to reveal workings of dementia genes

Frontotemporal lobar degeneration (FTLD) is a group of dementias that affect the frontal and temporal lobes of the brain and are characterised by behaviour and language dysfunction, rather than the memory loss associated with Alzheimer’s disease (AD).

FTLD, which affects about 50,000 people in the UK, also differs from AD in that it targets younger people: FTLD sufferers are usually in their 50s or 60s, although people as young as their 20s have also fallen victim to FTLD. AD sufferers tend to be older.

“Alzheimer’s patients lose their awareness of space and time, whereas FTLD can result in changes in personality as well as speech and language difficulties,” said Dr Stuart Pickering-Brown, who is leading the research.

“Sufferers can become apathetic or exhibit behaviour at the other extreme and lose normal social values which lead them to act inappropriately.

“Speech and language difficulties fall into two main types: sufferers can develop problems with grammar and pronunciation or have semantic dementia where they lose the information content of language.

Errors in two genes – tau and progranulin – have been identified as causes for FTLD but these only account for 10% of cases. The University of Manchester team plan to investigate the role other genes may play in the disease.

“Our research suggests other genes may be important in regulating the amount of tau and progranulin in the brain,” said Dr Pickering-Brown, who is based in the School of Translational Medicine.

“Progranulin is associated with wound healing and little is known about its function in the brain, so we now plan to study the effects of progranulin on cells and explore how it is affected by other genes.”

At the end of the five year study, the team hope to have a much clearer understanding of the genetic causes underlying FTLD.

“Understanding the biological problems that lead to FTLD will help in diagnosing the condition and ultimately allow us to find future therapies for patients.”

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