Alzheimer’s disease is a neurodegenerative condition that progressively interferes with an individual’s memory, thinking and behaviour. It is the most common form of dementia and is estimated that more than 1 million Canadians will be living with it by 2030.
With no cure for the disease, scientists around the world are conducting research that is leading to breakthroughs in the diagnosis, progression and prevention of Alzheimer’s. Dr. Julie Ottoy, scientist in the Hurvitz Brain Sciences Program, is one of the many researchers at Sunnybrook Research Institute, studying the pathophysiology of Alzheimer’s and what impacts it has on patient outcomes.
Dr. Ottoy’s interest in researching the causes and progression of Alzheimer’s disease started from her personal experiences. Like many Canadians, she has seen firsthand how the disease can impact the lives of family members and friends. Her experiences with her own loved ones and conversations with individuals with lived experience have played a pivotal part in shaping her work.
They remind me time and again that the research we do is about people, their families and their futures.
Dr. Ottoy’s research is working to answer some of the most fundamental questions surrounding Alzheimer’s. Who is most likely to develop Alzheimer’s? In what cases does the disease progress faster? Can we detect changes in the brain before symptoms appear?
Her work specifically focuses on better understanding mixed dementia. This is when Alzheimer’s disease occurs alongside vascular brain damage, which occurs when the blood vessels in our brain are affected and the blood flow to the brain is disrupted. Although mixed dementia is common, it’s not fully understood, making diagnosis and treatment challenging.
Using advanced neuroimaging techniques, like PET and MRI scans, blood-based biological markers, computational biology and AI-based analysis tools, Dr. Ottoy’s research focuses on two overarching themes:
- Mechanisms: To better understand how changes in our blood vessels and immune system contribute to brain changes seen in Alzheimer’s and mixed dementia.
- Biomarkers: To investigate novel biological markers that can aid researchers and clinicians in predicting the progression of these disorders in their early stages.
Her research looks for signs of vascular damage on brain scans, patterns of inflammation and the presence of toxic proteins that form into amyloid plaques and tau tangles. By combining this information, researchers can group patients into more specific subgroups based on the biological changes driving their disease, in turn driving more targeted intervention.
Photo illustration. Kevin Van Paassen/Sunnybrook Health Sciences Centre.
“Alzheimer’s is a very heterogeneous disease, meaning there is a number of different contributing factors and causes for the disease,” explains Dr. Ottoy. “By identifying different subgroups of patients using biomarkers, we are a step closer to creating more tailored treatments that match the individual needs of each patient more closely.”
Another area of her research investigates how well different brain regions connect with one another. The abnormal buildup of tau, one of the toxic proteins in Alzheimer’s disease, leads to cognitive decline in Alzheimer’s disease. Some studies suggest the way brain regions connect with each other is a key mechanism for the spreading of tau. Dr. Ottoy’s work studies these highly-connected regions and tau epicentres, to predict where the tau will build up next.
By studying the interface between the vascular system, immune cells and the spread of Alzheimer’s-specific toxic proteins throughout the brain, scientists can identify novel treatment targets, determine the best time and approach for disease intervention and develop new biomarkers that can inform future clinical trials and potential treatments. Understanding immuno-vascular contributions to dementia is important because both vascular and immune factors are modifiable.
With the advent of disease-modifying treatments, we are closer than ever in meaningfully slowing the progression of Alzheimer’s disease.
Today’s research lays the groundwork for larger-scale initiatives, including multi-site collaborations, like Toronto’s first 7-Tesla MRI, housed at Sunnybrook and part of the Toronto Neuro-Immunology/Imaging Consortium (TONIIC), a multi-site collaborative research initiative focused on neuroimmunology and neuroimaging for diseases such as Alzheimer’s. These research efforts will deepen understanding of disease mechanisms and aid in identifying new biomarkers and therapies.
“My hope is that these advancements will drive the development of combination treatment strategies that reach the clinic and accelerate progress toward precision medicine for neurodegenerative diseases.”
Dr. Ottoy’s research in immune-vascular contributions to dementia is funded by the Alzheimer’s Association and BrightFocus.
