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More than half a million Canadians are living with dementia and that number is expected to nearly double by the end of the decade, according to The Alzheimer Society of Canada, driven by aging demographics and longer lifespans.

Alzheimer’s is the leading cause of dementia and Canada, alongside the rest of the world, is headed for a crisis that will weigh on an already strained health care system – and so the race is on for a treatment or even a cure.

“There’s a huge, huge need to just increase the quality of life of individuals as we age, and there’s many different strategies to do that,” says Matthew Parsons, a professor of biomedical sciences at Memorial University in St. John’s.

One of those strategies is early detection of the disease to help slow cognitive decline, which Dr. Parsons and his team are working on at his university laboratory.

As Dr. Parsons explains, the brain’s neurons and cells are in constant communication through pockets of space between the cells, known as synapses. With Alzheimer’s and many other neurodegenerative diseases, the cells stop communicating, ultimately causing progressive cognitive decline.

“If you remove a brain cell’s ability to communicate with the neighbour, that brain cell is as good as dead,” Dr. Parsons explains. “In Alzheimer’s – and this seems to be true for many other neurodegenerative diseases – the connections… die before the cells die.”

Mounting evidence over the past two decades shows this synaptic dysfunction is at the root of the disease, and Dr. Parsons and his team want to know why that occurs.

“We do know now synapse loss is one of the best, if not the best, correlate of cognitive decline in Alzheimer’s disease,” he says. “So the more synapses you lose, the worse the cognitive decline is going to be.”

His team is interested in saving the synapses in order to save the brain. “There’s a lot of effort into [learning] exactly how the synapses are dying,” Dr. Parsons says. “If we know how the synapses are dying, the better the chance we have at developing therapeutics that can help maintain strong, healthy synapses over a lifetime.”

Predicting who might develop dementia

Many researchers worldwide are working to identify better biomarkers for Alzheimer’s to predict who will develop the disease so treatment can begin early.

“They’ve come a long way, but we still can’t predict with 100 per cent certainty who is definitely going to get Alzheimer’s disease,” Dr. Parsons says. “I think a better understanding of synapse death with earlier detection and intervention is a very promising strategy for the treatment, or even prevention, of Alzheimer’s disease.”

With the help of funding from the Alzheimer’s Society of Canada, the Memorial team is working with a known gene mutation linked to familial forms of Alzheimer’s, introducing them to brain cells or tissues in the lab, either in cell cultures or in animal models.

By doing that, the team hopes to figure out how the particular gene mutation affects the brain cell’s ability to communicate, which in turn leads to cell death and cognitive decline.

“Brain cells are very social and they like to communicate with each other. If you grow isolated neurons in a dish, and they’ll actually start connecting and forming synapses with each other,” Dr. Parsons says.

By comparing neurons that have the Alzheimer’s mutation to those that don’t, the team is finding clues to a potential therapy. The team’s work related to the Alzheimer’s society grant just ended but the research continues, Dr. Parsons says. The next phase is the preclinical assessment of gene therapy strategies that might restore synapse health. His lab is looking at potential targets for what could be causing the synaptic loss.

“We think we have a really good target now and if we can increase its expression in the brain we could save synapses later on,” he says.

Dr. Parson’s and his team are also conducting related research into Huntington’s disease, which bears certain similarities to Alzheimer’s and can also cause devastating cognitive decline.

Promising targets for new treatments on the horizon

Dr. Josée Guimond, the director of research, knowledge translation and exchange at the Alzheimer Society of Canada, says there are some promising targets for new treatments to slow or stop the progression of Alzheimer’s disease.

She points out the U.S. Food and Drug Administration approved a new treatment for earlier this year. Aduhelm, which targets a protein in the brain linked with Alzheimer’s, is recommended for patients with mild cognitive impairment.

The approval has been controversial because of mixed clinical trial results and U.S. Congress is looking into the approval process, but Dr. Guimond says it’s an important step as no other clinical treatment for the disease has been brought to market in nearly 20 years. Last year, there were 152 clinical trials assessing new therapies for Alzheimer’s.

“Alzheimer’s disease and other dementias are complex and not yet fully understood,” says Dr. Guimond, whose organization provides about $3-million a year for research. “While the number of potential treatment options currently being explored represents a significant improvement over the years, dementia research funding is still far behind any other major disease resulting in fewer drugs in the pipeline of clinical trials.”

On Nov. 30, The Globe and Mail hosted a virtual event called Regenerative medicine: Where will stem cells take us? Presented by Bayer, the webinar explored the way researchers are working on stem cell advances that could change the future of medicine. Read more here.