Biomedical Doctoral Awards

Chulmin Cho, McGill University, Jewish General Hospital, Lady Davis Institute

Project: Therapeutic importance of drebrin in amelioration of synaptic dysfunction in Alzheimer's disease

This project aims to uncover how synapses, or structures where signals are transmitted between brain cells, are lost in the early stages of Alzheimer’s disease. Synapse loss is more closely linked to dementia than other hallmarks of the disease, including brain plaques and tangles. Understanding how this loss occurs could provide clues for treatment. In particular, this project will determine whether the loss of a protein called drebrin has an important role to play in the loss of synapses.

Félix Jules, Université de Montréal, Centre de Recherche de l'hôpital Maisonneuve-Rosemont

Project: Characterization of a novel therapeutic target for the treatment of Alzheimer's disease

The brains of people with Alzheimer’s disease often contain plaques, formed from clumps of misfolded toxic protein fragments called amyloid beta. Researchers believe these plaques are partially responsible for the disease. Amyloid beta fragments form when enzymes ‘snip’ amyloid precursor protein (APP) into smaller pieces. The Beta-APP Cleaving Enzyme (BACE) makes the first snip. Those with Alzheimer’s disease have high levels of BACE in their brains. Understanding the biology of BACE could lead to new therapies for Alzheimer's disease.

Patricia Leighton, University of Alberta

Project: Uncovering mechanisms of A-beta 42 toxicity and normal roles of amyloid precursor protein (APP) using zebrafish models of Alzheimer’s disease
Recipient of the Annie Dakens Research Fund Award

The brains of people with Alzheimer’s disease often contain plaques, formed of clumps of misfolded proteins fragments called amyloid beta. Amyloid beta produced by neurons in one area of the brain triggers the death of nearby neurons. Amyloid beta also triggers the formation of tangles in the brain which disrupt signals from one neuron to another. Understanding how amyloid beta does this will help researchers design drugs to stop or reverse the progression of the disease. By genetically modifying zebrafish to show signs of Alzheimer's disease, more can be learned about the destructive work of amyloid beta and help better understand the role of amyloid beta precursor protein (APP), which breaks down to form amyloid beta protein fragments. Because APP seems to protect neurons, it is important to develop therapies that can block amyloid beta without inferring with APP's protective work.

Maxime Montembeault, Centre de Recherche de l'Institut Universitaire de Gériatrie de Montréal

Project: Characterization of semantic deficits and their anatomical bases in Alzheimer's disease and Semantic dementia patients

People with dementia often have trouble communicating which can sometimes lead to social isolation. These difficulties can also complicate how certain forms of dementia, including Alzheimer's disease (AD) and Semantic dementia (SD), are diagnosed and differentiated. By relating the symptoms of AD and SD to brain function, the results of this study could help distinguish the two disorders earlier and point the way to new interventions (such as language rehabilitation programs) to help maintain a person’s ability to communicate, as well as help target other treatments more effectively.

Franck Petry, Université Laval

Project: The effect of Type 1 diabetes on pathogenesis of tau in vivo

While we do not know exactly what causes Alzheimer’s disease, our genes and environment probably play important roles. One risk factor that has been identified is diabetes, but it’s not clear how diabetes increases the risk. Using mice, this project will explore how Type 1 diabetes might lead to Alzheimer’s disease. Understanding this relationship will have important implications for preventing and treating Alzheimer’s, including the possible use of anti-diabetic drugs.

Maria Lisa Putorti, McGill University

Project: Effects of Caspase-6 gene polymorphisms in Alzheimer's disease

The brains of people with Alzheimer’s disease contain greater amounts of a protein called Caspase-6 (Casp6), compared to those without the disease. This protein is responsible for the degeneration of neurons. But there are different forms of Casp6 and the role each of them plays is unknown. Certain forms of Casp6 increase the risk of Alzheimer’s disease while others decrease it. Identifying the different forms and levels of Casp6 in the DNA of people with Alzheimer's compared to those without the disease could lead to new diagnostic tests and drugs to decrease forms of Casp6 associated with Alzheimer’s disease.

Deborah Schwartz, Baycrest Centre for Geriatric Care (Toronto)

Project: The impact of visceral fat and sex-steroid hormones on brain health

Obesity appears to increase the risk of dementia, especially when fat builds up in the abdominal cavity between organs. Older women may be at increased risk because estrogen drops after menopause, triggering their bodies to store more fat in the abdomimal area. Estrogen also protects the brain from degenerating. This project will use a large population sample, the Saguenay-Youth Parent Study, consisting of 1,000 adolescents and their parents, to examine the effects of abdominal fat on brain health and the role sex and sex hormones play. Understanding risk factors for dementia is important for prevention and treatment strategies.

Amanda Tyndall, Hotchkiss Brain Institute, University of Calgary

Project: Cardiovascular fitness modulation of cerebrovascular reserve and cognition in older adults

People over the age of 55 experience declines in normal brain function and brain blood flow. Previous studies show that physically active older adults have increased brain blood flow and better cognition, but it is unclear why. To determine the reasons, 125 sedentary women and 125 sedentary men between the ages of 55 and 75 will be studied, taking baseline measurements of their physical fitness, brain blood flow and cognition. These groups will be retested after three months of exercise and once more after six months. This study could provide insights into how well exercise protects against Alzheimer’s disease and other dementias.

Yanlin Wang, University of Alberta

Project: Role of the insulin-like growth factor-II (IGF-II) receptor in beta-amyloid metabolism and its implications in Alzheimer’s disease pathology

Many researchers believe Alzheimer’s disease is caused by an overproduction and accumulation in the brain of toxic beta amyloid protein fragments. In neurons, the endosomal-lysosomal (EL) system is an important area for generating and clearing beta-amyloid. The insulin-like growth factor II (IGF-II) receptor is also responsible for transporting and regulating enzymes involved in these processes. Previous studies suggest increasing the function of the IGF-II receptor may protect neurons, whereas decreasing it can lead to neuron death after brain injury or exposure to toxins. To better understand why this happens, this research project will investigate cultured neurons, mice genetically modified to have Alzheimer’s and post-mortem human brain tissues in those with Alzheimer’s. Findings could point the way to early diagnosis and treatments.

Biomedical Post-doctoral Awards

Élizabeth Beauchesne, McGill University

Role of chronic hypertension-induced cerebrovascular oxidative stress and impaired abeta amyloid clearance across the blood-brain barrier in the pathogenesis of Alzheimer’s dementia
This project is jointly funded by the Alzheimer Society Research Program (ASRP) and the Fonds de recherche du Québec - Santé (FRQS), through the FRQS and ASC Partnership Program.

Many researchers believe Alzheimer’s disease is caused by an overproduction and accumulation in the brain of toxic beta amyloid protein fragments. While it’s not clear why this happens, we know proteins in the brain’s blood vessels play a role in clearing away beta amyloid. People with Alzheimer’s have damaged brain blood vessels, which may explain why beta amyloid accumulates. We don’t know why the brain’s blood vessels are damaged in those with Alzheimer’s, but we suspect oxidative stress has something to do with it. Since hypertension is associated with oxidative stress and hypertension is a risk factor for Alzheimer’s, this project will study their contribution to beta amyloid accumulation in mice genetically modified to have Alzheimer’s. A new class of nutraceutical antioxidant agents (Nrf2 inducers) will also be tested on Alzheimer’s mice with hypertension to see whether the drugs can prevent or reduce amyloid beta clearance problems.

Carrie Esopenko, Baycrest Geriatric Centre

Project: A multimodal neuroimaging and behavioural examination of the relationship between repetitive traumatic brain injuries and aging in retired National Hockey League players

This project will assess the relationship between repetitive concussions and aging in the brains of retired National Hockey League players. Studies show the greater the severity of the concussion, the greater the brain atrophy and functional changes. Research also shows that increasing age is linked to greater structural and functional brain changes. However, it’s not clear how concussion and age interact to affect brain health as we get older. Using cognitive tests and neuroimaging, this project will examine NHL alumni to pinpoint brain biomarkers associated with concussions and aging. A biomarker is a physical or chemical change in a person that indicates whether they have a disease and how far along it is. It allows doctors to diagnose a patient early, even before symptoms appear. In this case it could allow for early diagnosis of changes in the brain that could lead to dementia.

Shireen Hossain, McGill University

Project: Defining the process of aggregate-formation of AB42 peptide in Alzheimer’s disease and its relevance to toxicity and disease

The brains of people with Alzheimer’s disease often contain plaques, made up of clumps of misfolded toxic protein fragments called amyloid beta. Researchers believe these plaques are partially responsible for Alzheimer’s. These protein fragments are formed from a larger protein – the amyloid beta precursor protein (APP) – after it is ‘snipped’ by a series of enzymes. The resulting amyloid beta fragments include the non-toxic AB40 and AB38 fragments, as well as the toxic, plaque-forming AB42 fragment. Studying cell cultures and mice genetically modified to have Alzheimer’s disease will provide a clearer picture of how AB42 is created and leads to the disease. Findings could help researchers develop drugs to stop its accumulation.