Photo : Dr. Hideto Takahashi
September 21 marks World Alzheimer's Awareness Day. The IRCM and its Foundation are actively involved in the fight against dementia..
Dr. Hideto Takahashi's research specifically offers hope for drug development. An overview of his work and its significance:
As we age, our memory sometimes fails; this is part of the normal aging process. People with dementia, of which Alzheimer's is the most common form, have it worse: they lose track of time and space, struggle to learn new things or perform familiar tasks. They forget little things, words and even the names of their loved ones and eventually lose the ability to take care of themselves. Most people experience the first symptoms of the disease in their mid-sixties. The disease strikes women more often (65%) than men, and is fatal.
We all know someone with Alzheimer's in our family or community. The exact cause of the disease remains unknown. However, the consequences on the quality of life of people with dementia and their caregivers, as well as the economic impact of these diseases on the health care system are colossal.
In Canada, 75,000 people are diagnosed with dementia each year - Alzheimer's accounts for 60-80% of these - and it is crucial that we find ways to prevent it.
A new therapeutic target called Neurexin
Imagine that brain cells are like little islands that communicate with each other through chemical bridges. These connectors are the synapses that help us process information, learn and remember. To lose synapses is to lose these cognitive functions. Their loss is also a known early pathological feature of Alzheimer's disease.
Advances in science have identified an abnormal accumulation of a toxic molecule in the brain called beta-amyloid. How this affects cognitive impairment was a mystery that IRCM neuroscientist Hideto Takahashi was able to unravel.
Dr. Takahashi's laboratory discovered the direct link between the toxic molecule and neurexins, the molecules that play a key role in synapse formation and brain function, thus revealing the pathological mechanism of Alzheimer's disease: beta-amyloid disrupts neurexin function and breaks the chemical bridge, permanently. His team was also able to identify binding proteins that have the potential to protect neurexins from the disruptive action of the toxic molecule. Even more exciting: Hideto Takahashi discovered the same interaction with another toxic molecule found in dementia with Lewy bodies as well as Parkinson's with dementia. These discoveries at the IRCM raise the hope that neurexins could be a common therapeutic target for all of these degenerative diseases.
Dr. Takahashi's team hopes to take the research further and test their hypotheses on the learning and memory abilities of mice, and ultimately find drugs.
"We hope to show that by blocking the interaction between the protein and the toxic molecule, we can save the synapses before they are damaged. This would bring us closer to finding drugs that can treat or even prevent neurodegeneration in people with early dementia. We know that genetic mutations in neurexins are linked to autism, schizophrenia and other diseases that affect cognitive function. By better understanding the pathological role that neurexins play in brain structure and function, we will also shed new light on these other neurological disorders."
Hideto Takahashi, research unit director
Together, let's save our seniors from neurodegeneration before it's too late
Montreal is the hub of neuroscience research in Canada and the IRCM is one of its flagship institutions. Our researchers work in an environment of technological innovation that fosters interdisciplinary collaboration - an environment conducive to new ideas and their exploration. Hideto Takahashi, Director of the Synapse Development and Plasticity Unit, is a prime example.
Although there is a lot of research on Alzheimer's and dementia, most of it focuses on the toxic molecule, not the molecule's receptors, as Dr. Takahashi's lab does. Supported by the Canadian Institutes of Health Research and the Alzheimer Society of Canada, he has been at the forefront of research into understanding these complex cohesive mechanisms for five years. His lab will inherit state-of-the-art equipment after winning, as part of a group of leading neuroscientists at the IRCM, $7.9 million in funding through a Canada Foundation for Innovation (CFI) competition.
Hideto Takahashi's project is based on a comprehensive approach to research at the molecular, cellular, and behavioral levels of the mouse that will exploit multiple technology platforms; provide trainees with an excellent scientific and academic training environment; and help develop high-quality researchers who will contribute to maintaining Montreal's status as a leader in neuroscience research.
The Foundation's essential role in supporting research
The IRCM Foundation, through its major campaign Inspired by Life, aims to support Hideto Takahashi's ongoing work that has the potential to lead to the discovery of drugs that can alleviate the burden of dementia that will affect a growing number of our seniors.
