DAY 1 – OCTOBER 12, 2021

Here are the links to the content presented during DAY 1.

SESSION 1    CIHR MEETS WITH CCNA PARTNERS (BY INVITATION ONLY)

No recording available

SESSION 2    OPENING SESSION

Land acknowledgment, State of the Consortium and Update on CCNA

SPEAKER: Dr Howard Chertkow, Scientific Director, CCNA

SESSION 3     INTERACTIVE SESSION ON MECHANISMS

This session is an opportunity to learn about work taking place across different teams. It will allow to interact, discuss, and discover new potential collaborations and foster connectivity. This session includes six short presentations on Mechanisms that lead to dementia and add to dementia risk by CCNA Members and Trainees. The presentations will be followed by a discussion with the audience.

MODERATOR: Gillian Einstein

1. Relationship between cerebrovascular pathology and resting-state functional connectivity in Alzheimer’s disease and vascular cognitive impairment and dementia: A systematic review – AmanPreet Badhwar
2. Metabolic dysregulation in early Alzheimer’s disease – Lewis Joo
3. Why is hearing loss a risk factor for dementia? An overview of possible mechanisms – Natalie Phillips
4. Influence of sex on pathology and behaviour in the 3xTg-AD mouse model of Alzheimer’s disease – Margaret Fahnestock
5. The intersection between genetics, epigenetics & aging in neurodegenerative diseases – Ekaterina Rogaeva
6. Sex differences in the neural correlates of neuropsychiatric symptoms in neurodegenerative disorders – Shankar Tumati

SESSION 4     PANEL – Perspectives on bringing research from bed to bedside

In this panel, we will hear three stories from CCNA researchers with experience bringing their work from the bench to the bedside – from the research lab to clinical use. The stories will cover experiences of success as well as failure, challenges, lessons learned and important milestones along the way. The discussion will draw observations about partnership vs. ownership in commercial initiatives, funding paths, and the involvement of people with lived experience of dementia and other stakeholders in product and business development.

MODERATOR: Catherine Ferland

SESSION 5    KEYNOTE PRESENTATION

Noninvasive sensory stimulation to induce gamma entrainment and neuroprotection

With Li-Huei Tsai, Ph.D. Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology

Rhythmic neural activity in the gamma range (30-80 Hz) is modulated during various aspects of cognitive function and has been shown to be disrupted in several neurological conditions, including Alzheimer’s disease (AD). It is well established that local network oscillations at specific frequencies can be induced in cortical areas using sensory stimuli. We have applied this approach, which we term Gamma ENtrainment Using Sensory stimuli (GENUS), using patterned light and sound stimulation at 40 Hz in AD model mice. Remarkably, GENUS augmented gamma oscillation power in multiple brain regions. Moreover, chronic application led to marked reduction of amyloid and tau pathology, attenuated neurodegeneration, and improved cognitive function in multiple AD mouse models. These beneficial effects elicited by GENUS are likely to be mediated by microglia activation, and increased capillary mediated clearance.  In humans, combined light and sound stimulation increases gamma oscillation power in extended brain regions including deep brain areas such as the amygdala, hippocampus and posterior insula. We found that GENUS is safe even after prolonged exposure. Preliminary data suggests that GENUS stabilized hippocampal volume in AD subjects and maintained functional connectivity in the brain. These results support further evaluation of GENUS in larger and longer clinical trials to evaluate its potential as a disease modifying therapeutic for Alzheimer’s disease.

PRESENTER: Ted Fon

SESSION 6    BEER & GREET (live gathering) 

No recording available

BIOS

Session 3

Gillian Einstein is The Wilfred and Joyce Posluns Chair in Women’s Brain Health and Aging, Professor of Psychology at the University of Toronto and Guest Professor of Gender and Health at Linköping University in Linköping, Sweden. She is an Adjunct Scientist at Women’s College Research Institute and at the Rotman Research Institute in Toronto. She is a board member of the International Gender Medicine Society, Chair of the Canadian Institutes of Health’s Institute of Gender and Health Advisory Board, and Founder of the Canadian Organization of Gender and Sex (COGS) Research. She is Lead of the Women, Sex, Gender, and Dementia cross-cutting program of the Canadian Consortium on Neurodegeneration and Aging. Her current research is on the effects of early life ovarian removal on women’s memory, brains, and long term risk of Alzheimer disease with the overarching question: How do both sex and gender mediate women’s brain health?

AmanPreet Badhwar is an Assistant Professor at the University of Montreal, Faculty of Medicine, Department of Pharmacology and Physiology, and a researcher at the Centre de recherche de l’Institut universitaire de gériatrie de Montréal. She is a CCNA member (Teams 7 & 9), Trainee Liaison-Team 9, and the CCNA Trainee Society past-Chair. Dr. Badhwar’s academic path has been to study neurological disease by combining different data types, starting with small-scale genetics and brain imaging early in her career, and progressively moving to “big-data-analytics” in Alzheimer’s disease. Dr. Badhwar directs the Multiomics Investigation of Neurodegenerative Diseases (MIND) Lab that focuses on integrating observations from in-vivo imaging and molecular ‘omics’ in the study of age-related dementias, with the goal of discovering new biomarkers and therapeutic targets, and improving methods to speed the drug discovery process. Dr. Badhwar has held multiple prestigious scholarships/awards, and was recently awarded the Fonds de recherche du Québec-Chercheur-boursiers Junior 1.

Lewis Joo’s research interest lies in the application of medical imaging and analysis for the characterization of neurodegenerative diseases. Currently, he is primarily focused on the functional characterization of Alzheimer’s disease in the prodromal stage using a rat model of Alzheimer’s disease. This involved broad assessment of structural and functional alterations using two-photon fluorescence microscopy, MRI and electrophysiology. He has an immense interest in medical imaging modalities and the benefits of multimodal assessment for neurodegenerative diseases which have prompted him to develop multiple methodological and procedural improvements for preclinical functional imaging studies. In particular, my recent focus has been on the adoption of awake imaging into the imaging protocol for future experiments.

Natalie Phillips (Ph.D., Clinical Psychology, Dalhousie, 1996) is a Professor in the Department of Psychology, Concordia University, and holds the Concordia University Research Chair (Tier 1) in Sensory-Cognitive Health in Aging and Dementia. Dr. Phillips examines the neuropsychology of healthy aging and Alzheimer’s disease. She studies the relationship between our senses and our cognitive abilities and language processing in older adults, including those who are bilingual. Dr. Phillips is one of the principal developers of the Montreal Cognitive Assessment (MoCA), a cognitive screening instrument used globally for the assessment of mild cognitive impairment. She is the Associate Scientific Director of the Canadian Consortium on Neurodegeneration in Aging (CCNA, http://ccna-ccnv.ca/en/), Canada’s national research consortium on dementia. She is the one of the organizing neuropsychologists for the COMPASS-ND study, and is founding leader of CCNA Team 17 (http://ccna-ccnv.ca/en/research/theme-3/), which examines issues of sensory health and cognitive function in people with dementia.

Margaret Fahnestock received her Honours B.Sc. in Biological Sciences from Stanford and her Ph.D. in Biochemistry from the University of California, Berkeley. Following postdoctoral work in Endocrinology at Baylor and Neurobiology at Stanford, she moved to the Stanford Research Institute, where her team developed base-by-base DNA sequencing, the basis for today’s DNA sequencing machines. After a sabbatical in Neurology at UCSF, Dr. Fahnestock moved to McMaster University. She is now a Full Professor in McMaster’s Psychiatry and Behavioural Neurosciences Department and co-Lead for CCNA Team 2. Dr. Fahnestock is internationally recognized for her work in neurotrophin regulation, expression and signalling. Her research focuses on neurotrophic factor biosynthesis and regulation, their receptors, and their roles in Alzheimer’s disease and other neurological disorders. She was the first to describe biologically active proNGF in the brain and its elevation in Alzheimer’s disease. She has published over 100 peer-reviewed articles and has been funded continuously for over 35 years.

Ekaterina Rogaeva’s graduate degree (1983) and PhD in Biochemistry (1988) were obtained at Moscow State University. For the past 30 years, she has been doing genetic research at the University of Toronto in the Tanz Centre for Research in Neurodegenerative Diseases. In 2013, she obtained the Lewy Body Chair position, and was promoted to Full Professor in 2015. Dr. Rogaeva contributed to 350 peer-reviewed papers (h-index=92; Citations=46,639). Most of these papers are focused on the development of effective genetic testing for neurodegenerative diseases (eg, Alzheimer’s Disease, ALS and Parkinson’s Disease). For instance, she played a central role in the discovery of several genes associated with the early- and late-onset forms of Alzheimer’s Disease (eg, PSEN1, PSEN2 and SORL1). More recently, Dr. Rogaeva’s studies have focused on the link between neurodegenerative disorders and epigenetic events, such as age-related DNA methylation reflecting biological aging.

Shankar Tumati is a postdoctoral fellow with CCNA’s Team 11 (Prevention & Treatment of Neuropsychiatric Symptoms). Dr. Tumati’s research is focused on understanding the neurocognitive mechanisms of neuropsychiatric symptoms in dementia using structural and functional MRI imaging. In his PhD studies in the Netherlands, he investigated functional MRI and MR-spectroscopy changes in association with apathy in patients with mild cognitive impairment. In his postdoctoral work in Ottawa, he studied the temporal structure of neural activity and its abnormalities in psychiatric disorders. With Team 11, he is investigating whether the neural correlates of neuropsychiatric symptoms are similar across neurodegenerative disorders and whether there are sex-specific associations. He is also working on developing interventions to treat these symptoms. When not analyzing data, he spends time outdoors and likes to cook Indian recipes.

Session 4

Catherine Ferland, PhD, is the Chief Research and Programs Officer at Brain Canada. Dr. Ferland is a trained neurophysiologist interested in the endogenous mechanisms of pain modulation. She has a broad academic background including Kinesiology, Veterinary Biomedicine and Clinical Neurophysiology. She was appointed Assistant Professor in the Department of Anesthesia at McGill University, with an affiliation to the Integrated Program in Neuroscience. Supported by a Fonds de recherche du Quebec-Santé Research Scholar – Junior 1, she put in place a research program integrating basic, translational and clinical initiatives for the prevention of chronic post-surgical pain. Dr. Ferland has acted on several committees at the local and international levels and has been a panel expert on several review committees for the CIHR, NSERC and FRQ-S.

Neil Cashman is co-founder and CSO of ProMIS Neurosciences, a Canadian biotech company focused on therapeutics and diagnostics for neurodegenerative diseases. He is also a Professor of Medicine at the University of British Columbia, where his research lab is focused on the role of protein misfolding in neurodegenerative diseases, particularly ALS. He is one of the Director of the UBC ALS Centre at the G.F. Strong Rehabilitation Centre which is attached to UBC.

Sultan Darvesh completed his PhD (Organic Chemistry) and Postdoctoral Fellowship (Molecular Biology) at the University of New Brunswick, his MD and residency (Neurology) at Dalhousie University, and his Fellowship (Behavioural Neurology) at The Baycrest Centre for Geriatric Care. He is a Professor and Staff Neurologist, in the Department of Medicine (Neurology and Geriatric Medicine), at the QEII Health Sciences Centre, Halifax, Canada; he was cross-appointed to the Department of Medical Neuroscience, Dalhousie University and to the DMRF Irene MacDonald Sobey Chair in Curative Approaches to Alzheimer’s Disease, Dalhousie University. Dr. Darvesh combines basic and clinical research related to neurodegenerative diseases. As a medicinal chemist and a behavioural neurologist, his research focuses on the neurochemistry and neurobiology of cholinesterases in the development of neurodegenerative disorders. He is concerned with developing diagnostics and therapeutics for Alzheimer’s disease. This research is carried out in conjunction with assessment and management of cognitively impaired patients. He has published over 100 publications and is an inventor with 14 patents and 1 copyright.

JoAnne McLaurin is a Senior Scientist at the Sunnybrook Research Institute within the division of Biological Sciences, holds the Canada Research Chair in Alzheimer’s disease Therapeutics, Tier 1; co-leads Theme 1 Primary Prevention in Dementia for the Canadian Consortium on Neurodegeneration in Aging; and is a Professor in the Department of Laboratory Medicine and Pathobiology at the University of Toronto. She has contributed a body of work on the detrimental effects of Aβ accumulation and the benefits of reducing Aβ, including the discovery that perivascular macrophages are important for Aβ clearance in arterioles; on the loss and rescue of GABAergic neurons in the hippocampus; on the effects on neurogenesis with aging; on neuroinflammation as well as on Aβ clearance pathways. Dr. McLaurin’s present focus is molecular medicine and biological research to determine which factors impact risk and progression of age-related brain disorders and, specifically, the discovery of much-needed treatments for Alzheimer’s disease and dementia.

Alison Sekuler (BA, Mathematics & Psychology, Pomona College; PhD, Psychology, University of California Berkeley) is the Vice President Research and Sandra A. Rotman Chair in Cognitive Neuroscience at Baycrest Health Sciences, and Managing Director of the Rotman Research Institute and the Centre for Aging and Brain Health Innovation (CABHI). A Professor at the University of Toronto and McMaster University, Dr. Sekuler aims to develop methods to detect, prevent, and treat age-related sensory- and cognitive-decline. She currently Chairs NSERC’s Public Value Impact Panel for the Alliance program, as well as serving on the Boards and advisory committees for Hamilton Health Sciences, Western University’s BrainsCAN and York University’s VISTA Innovation programs, and the Canadian Brain Research Strategy. Among Dr. Sekuler’s many awards, she was the country’s first Canada Research Chair in Cognitive Neuroscience, and was recognized in 2019 as one of Canada’s Top 100 Most Powerful Women by the Women’s Executive Network.

Session 5

Li-Huei Tsai is the Picower Professor of Neuroscience at MIT and has been director of The Picower Institute for Learning and Memory since 2009. Her lab investigates disorders of memory and cognition, in particular neurodegenerative conditions such as Alzheimer’s disease, at scales ranging from the molecular and cellular to that of circuits and systems. Her work has highlighted important roles for the dysregulation of chromatin and genomic integrity in neurodegeneration as well as the kinase Cdk5. These lines of research have produced preclinical interventions, such as specific molecular inhibitors, to repair dysregulated pathways. Her lab has also pioneered the use of patient-derived induced pluripotent stem cell cultures and CRISPR gene editing to investigate how Alzheimer’s risk genes lead to disease pathology. Tsai also co-leads a collaboration conducting “big data” omics analyses of post-mortem Alzheimer’s brains to identify and study novel disease pathways. Tsai’s work investigating dysfunction in neural circuits and networks has led to the discovery in multiple mouse models that sensory stimulation of 40 Hz gamma oscillation power and the associated synchrony, which is diminished in Alzheimer’s disease, produce widespread ameliorative effects including a reduction in amyloid and tau pathology, prevention of neurodegeneration and synapse loss, and preservation of learning and memory. In this method, called GENUS, for Gamma ENtrainment Using Sensory stimuli, subjects are exposed to light and/or sound oscillating at 40Hz. Studies to understand the mechanistic basis of GENUS’ effects are ongoing, but a major fundamental insight is that sensory entrainment of 40 Hz rhythms recruits not only neurons but also glial cells and vasculature. The lab has since begun a series of human clinical studies to test the safety and efficacy of GENUS in volunteers with early or mild cognitive impairment and further studies to test other disease indications for sensory rhythm entrainment are planned.

Ted Fon is the Scientific Director of the Montreal Neurological Institute and Professor in the Department of Neurology and Neurosurgery at McGill University. He is a clinician-scientist and attending neurologist specializing in movement disorders. He is the Director of the McGill Parkinson Program, a Parkinson Foundation (PF) Center of Excellence and Director and co-founder of the FRQS Quebec Parkinson Network. His research focuses on the molecular events leading to the neuronal degeneration in Parkinson’s disease (PD). He is particularly interested in the function and cell biology of PD genes. His hope is that work in this area could provide clues about disease mechanisms and potentially lead to innovative new therapeutic strategies. His work has been published in prestigious journals including Science (Trempe et al. 2013), Nature (Koyano et al. 2014) Nature Cell Biology (Fallon et al. 2006), ELife (McLelland et al. 2018), Molecular Cell (Trempe et al. 2009), Nature Communications (Tang et al. 2017), Neuron (Kalia et al. 2004), Journal of Cell Biology (McLelland et al. 2016), EMBO J. (McLelland et al. 2014 and Durcan et al. 2014), Genes and Development (Durcan and Fon 2015), EMBO Reports (Greene et al. 2012) and Human Molecular Genetics (Durcan et al. 2011). He also leads the Open Science Drug Discovery initiative at the Montreal Neurological Institute. Dr. Fon has received several awards during the course of his career including the CIHR Clinician-Scientist award, the Prix de Jeune Chercheur Blaise Pascal, a National Scholar award of the FRQS and the EJLB Foundation Scholar. He is currently an elected member of the American Society for Clinical Investigation (ASCI) and a Canada Research Chair (Tier 1) in Parkinson’s Disease. His research is supported by the CIHR (Foundation grant), CQDM, Brain Canada, Parkinson Canada, CCNA and the Michael J. Fox Foundation.