Researchers find cause of inherited form of early onset dementia

Vancouver, BC – The genetic cause of the second most common type of dementia in those under the age of 65 has been discovered by researchers at the University of British Columbia and Vancouver Coastal Health Research Institute (VCHRI).

Mutations in the progranulin gene cause an inherited form of frontotemporal dementia (FTD), according to findings made by UBC researchers professor Ian Mackenzie, of the deptartment of pathology and laboratory medicine, and professor Howard Feldman, director of the UBC hospital clinic for alzheimer’s disease and related disorders.

The findings were published online in Nature.

The scientists, working together with colleagues at the Mayo Clinic, led by Dr Mike Hutton, have identified mutations in the progranulin gene. Drs Mackenzie and Feldman and are both members of VCHRI, clinicians at Vancouver General Hospital and UBC Hospital and members of the brain research centre at UBC Hospital.

“The discovery is particularly exciting because the way these mutations cause dementia was quite unsuspected and opens the door to new possibilities for treatment,” says Dr Mackenzie.

FTD represents approximately 15% of all dementia, affects both men and women, usually between 50-60 years old at the time of onset and is inherited in about half of cases. It typically leads to a devastating impairment in language until the patient is virtually mute, and causes serious changes in behaviour such as compulsive buying or eating, and disturbed social functioning. Unlike Alzheimer’s disease, the most common type of dementia in all age groups, patients with FTD may retain memory until later in the course of the disease. After diagnosis, the expected lifespan is 5-10 years.

Until now, most inherited forms of dementia, such as familial Alzheimer’s and Parkinson’s diseases, have been associated with mutant genes that cause an accumulation of disease-specific proteins within brain cells, creating a toxic effect and prematurely killing neurons.

The investigators have discovered that mutations in the progranulin gene that cause FTD results in an underproduction of the progranulin protein – an essential growth factor needed for nerve cell survival. Uncovering this unique mechanism of nerve cell degeneration means scientists can now explore entirely new treatment strategies.

“Treatment may be successful if we can find a way to deliver progranulin to nerve cells,” says Dr Feldman, who adds that the discovery is an excellent example of clinicians, neuroscience researchers and geneticists working together to accelerate discovery.

The research team will now develop screening tests for families with FTD, explore genetic and non-genetic therapies, and determine if the gene plays a role in more common degenerative diseases such as other forms of dementia and amyotrophic lateral sclerosis (ALS).