A Brief Description of Currently Funded Research Grants
2009-2010
Comparative studies of memory and attention/executive abilities in individuals with Alzheimer’s disease and Parkinson’s disease, with and without dementia.
Dr. Nicole Caza
Institut universitaire de gériatrie de Montréal
Montreal, Quebec
Introduction: Individuals with Alzheimer’s and Parkinson’s disease with and without dementia have common clinical signs. Early on, patients present with attention deficit, difficulty in strategically solving problems (called “executive deficit”), and memory problems. However, past research suggests that the relative degree of impairment in memory and attention/executive abilities may vary according to diagnostic group, resulting in distinct patterns of cognitive impairment. Understanding how memory and attention/executive abilities are differentially impaired in Alzheimer’s and Parkinson’s disease is important for successful patient management.
Projected benefits and application of findings: Understanding how memory and attention/executive abilities are uniquely affected in individuals with Alzheimer’s disease and Parkinson’s disease with and without dementia will help determine which cognitive function is more likely to decline and/or have an impact on the patient’s daily activities. In turn, this will result in more functional families which can make appropriate decisions. Better characterization of memory and attention/executive abilities will also help to customize intervention program, resulting in healthier patients. Importantly, all of the tasks in this proposal can be adapted and used as part of a neuropsychological evaluation. False recognition and source memory are both clinically and theoretically important as they provide clues concerning the underlying processes involved in human memory, and highlight reconstructive aspect of memory, which few studies have addressed in clinical populations. Methods and knowledge developed in this research can be 1) used in clinical trials to examine which processes are targeted by the therapeutic agent, and 2) extended to include individuals with Lewy Body dementia to enlighten its relationship with other dementias, especially in Parkinson’s disease.
Direct in vivo imaging of the effects of early-life seizures on brain circuit structure and function
Dr. Kurt Haas
University of British Columbia
Vancouver, British Columbia
Purpose of the research: To identify how seizures during early brain development disrupt normal structural and functional brain circuit plasticity, potentially creating dysfunctional circuits underlying neurological disorders later in life.
Project benefits and application of findings: Results will provide critical insight to the susceptibility of the developing brain to early-life seizures. These results are of critical clinical importance, given the high incidence of seizures in humans during critical periods of brain development. Furthermore, by studying the effects of anti-epileptic drugs on brain neuron growth in the same model system, clinicians will be able to balance the risks of alterations induced by seizures and potential therapies. Future applications of this important new model of developmental seizures will be to screen for new therapeutics to prevent or counter seizure induced damage.
The role of microRNAs in tau alternative splicing and sporadic tauopathies
Dr. Sébastien Hébert
Centre de Recherche du CHUQ (CHUL)
Québec, Quebec
Introduction: Tauopathies are a group of devastating neurodegenerative disorders characterized by abnormal intracellular deposits of the microtubule-associated protein tau. Both genetic and biochemical evidences suggest that changes in tau messenger RNA (mRNA) alternative splicing of can cause tau aggregation and lead to the development of tauopathies like frontotemporal lobar degeneration (FTLD). MicroRNAs, small endogenous non-coding RNAs, have recently emerged as major regulators of biological pathways, whereas loss of microRNA pathways leads to neurodegeneration in animals. Recent studies performed in humans support the idea that changes in microRNA expression profiles can contribute significantly to risk for major neurodegenerative diseases such as Alzheimer’s disease (which contain tau inclusions). Interestingly, a key role for microRNAs in regulating neuronal-specific mRNA splicing has recently been reported. Whether changes in the microRNA network contribute to the development of tauopathies (like FTLD) via abnormal regulation of tau mRNA splicing remains therefore an interesting possibility.
Projected benefits and applications of findings: MicroRNAs have only recently been involved in human disease but research has mainly focused on cancer. We believe that this line of research is very exciting because it contributes to the growing field of microRNAs in neurodegeneration and it sheds a totally new light on the regulation of genes and cellular pathways potentially involved in tauopathies. From our preliminary data, it looks like that misregulation of microRNAs could turn out to be a major cause of sporadic FTLD.
Mapping Neuro-Inflammation in Alzheimer's Disease with [18F]-Feppa-A New Ligand for the Peripheral Benzodiazepine Receptor (PBR)
Dr. Romina Mizrahi
Dr. Sylvain Houle
Dr. Pablo Rusjan
Dr. Alan Wilson
Centre for Addiction and Mental Health
Toronto, Ontario
Introduction : Alzheimer’s disease (AD) is a progressive disease that affects mostly elderly people. In the AD brain damaged neurons provide obvious stimuli for neuroinflammation. Further, nonsteroid anti-inflammatory drugs (NSAIDs) may diminish the risk of developing AD. The peripheral benzodiazepine receptor (PBR) has been implicated in various functions such the inflammation response seen in AD. Scientists across the world have looked at PBRs in the brain of persons with AD, and found that their levels are elevated. However, the method they used was not accurate enough. We have recently developed a method to measure PBR in the human brain, using a radioactive dye called [18F]-FEPPA that can exquisitely “sense” PBR levels in the brain when looked at with positron emission tomography (PET).
Projected benefits and applications of findings: Upon validation as a PET dye capable of measuring the PBR, [18F]-FEPPA will provide a unique opportunity to measure neuro-inflammation in human brain. Thus, imaging the PBR may help develop early detection strategies for AD and understand anti-inflammatory treatments as well as other potential approaches that may help slow the progression or delay the onset of AD.