Two groundbreaking discoveries by an Irish scientist, separated by almost 20 years, have shed significant new light on the causes of dementia and Parkinson’s disease.

Back in 1994, Prof Tim Lynch was training as a neurologist in the United States when his research team made a landmark finding of the first mutation of the tau gene that causes a form of dementia.

Working in Columbia-Presbyterian Medical Center, New York, the team discovered the mutation responsible for frontotemporal dementia – a form of the disease occurring in the part of the brain behind the forehead and ears – in an Irish-American family.

This discovery changed the science and direction of dementia research across the globe, including work on Alzheimer’s disease, because the tau protein is also abnormal in the brains of Alzheimer patients.

At the time, the team predicted all the sites within the stem loop of the gene where mutations over time would be found, and also predicted no mutations would be within the loop region.

In the years that have passed, all but one of the predicted tau mutations were found, thereby further unlocking the mysteries of brain degeneration.

It wasn’t until two years ago that the final mutation was uncovered and, in the words of Lynch, “the loop was closed”.

This happened on the other side of the Atlantic when a man presented to his neurology clinic at the Dublin Neurological Institute at the Mater Misericordiae University Hospital in Dublin with short-term memory loss and a changed personality.

Peculiar clinical pattern

The 44-year-old farmer showed signs of disinhibition and impulsivity, but was also apathetic and lacked motivation, according to the report published recently in Brain journal.

His sense of humour was altered and he enjoyed playing practical jokes.

“I had been waiting for something like this for over 15 years, to complete the circle that started with the initial research in the US.

“The patient had a family history of neurodegenerative diseases that had been previously labelled as Alzheimer’s but the clinical pattern was peculiar,” says Lynch.

The Mater team examined a number of the man’s siblings, who were found to have either personality change or atypical parkinsonism, thereby indicating the importance of the tau gene for Parkinson’s disease as well as dementia.

“Thanks to our previous work and recognition of the importance of the ‘missing tau mutations’ we were in a position to realise that we had found the missing tau mutation and that this gene change was causing the disorder in the family.”

Lynch says Ireland is an ideal country in which to carry out neurological research because the population is genetically homogenous yet large enough to accommodate a sufficient variety of conditions.

Researchers also appreciate the traditionally large size of Irish families as the large families make identification of causative genes in brain conditions easier.

The tau loop mutation causes frontotemporal dementia, which accounts for roughly one in five dementia cases, behind Alzheimer’s and stroke.

“It’s a particularly nasty form of the disease, one that robs patients of their personality.

“It differs in this respect from Alzheimer’s, where the personality is preserved. It’s also a tricky diagnosis, often mistaken for other issues,” says Lynch.

Amyloid protein mutations

In recent years, much research has focused on mutations in the amyloid protein as the potential cause of degenerative diseases in the brain.

Lynch, though, believes tau offers greater potential for unlocking the dark secrets of dementia and other neurological disorders.

Given the fact that more than 700,000 people in Ireland suffer from some form of neurological condition, with this number set to increase as the population ages, the importance of brain research cannot be underestimated.

A cure for dementia is perhaps five to 10 years away, he estimates.

“We can now stop multiple sclerosis in its tracks using biologic agents, and we hope to be doing the same with dementia in the next 10 years.”

Even delaying the onset of dementia by five years would confer an enormous financial benefit on a hard-pressed health system, he points out.

“The result of this research will be used to bring new awareness to this particular field of neurology and result in new interest and funding for the development of much-needed novel treatments.”