Ms. Marie-Ann Wasef
Supervisors: Dr. Darlene Skinner and Dr. Susan Walling
Ms. Wasef was awarded the 2019 ARC-NL Graduate Fellowship for her project entitled,
Targeting the Earliest Asymptomatic Stages of Alzheimer’s Disease Using a New Animal Model of Alzheimer’s Disease.
ARC-NL: What piqued your interest in this area of research?
With an ageing population and the inevitable increase in patients and families affected by the disease, research studying Alzheimer disease is critical. To date, there is no cure for the disease. While medications may temporarily improve or slow the progression of symptoms, more research is required to diagnose the disease in its early stages in hopes of being able to treat the disease before it progresses. Furthermore, having had a family member who died and was diagnosed with the disease has played a big part in my passion for researching the disease. Experiencing first-hand how devastating the disease can be motivated me to become involved in this area of research.
ARC-NL: Can you please provide a brief synopsis of your specific project?
Abnormally phosphorylated tau is a protein commonly associated with Alzheimer’s disease. Braak and Del Tredici (2011) have identified a noradrenergic nucleus, the locus coeruleus (LC), as the brain region to first express abnormal tau. Using a TH-Cre transgenic rat model of pretangle Alzheimer’s disease, we attempted to model the earliest prodromal stages seen in humans. We infused an adeno-associated virus (AAV) with a transgene coding a pseudophosphorylated human tau, htauE14, into the locus coeruleus and examined the behavioural consequences using four behavioural tests to assess memory, at one to three months and four to six months post-infusion. Selective htauE14-GFP expression in locus coeruleus neurons was confirmed using double immunolabelling for tyrosine hydroxylase and green fluorescent protein (GFP). We showed that greater than 93% of locus coeruleus neurons expressed GFP at one to three months and four to six months post-infusion. Using an antibody against dopamine-b-hydroxylase, we showed higher relative optical density for LC-htauE14 infused rats at one to three months post-infusion in CA1 and the subgranular zone, suggesting htauE14-mediated changes in locus coeruleus projections. Behavioural assays indicate subtle, sex-dependent impairment on hippocampal-dependent spatial memory. These results suggest that AAV-htauE14 is selectively expressed in LC neurons and can modify noradrenergic input to memory structures. Behavioural deficits may become more apparent if the LC-mediated projections are lost as animals age.
ARC-NL: How did getting the support of the ARC-NL Graduate Fellowship assist you with your project?
Financial support from ARC-NL allowed me to focus on my research instead of working while conducting research. With this extra time that I could devote to my research, I conducted more experiments than I could have if I had to work a part-time job. Ultimately, this funding allowed me to take more steps forward and answer even more questions.
ARC-NL: How do you feel your research will benefit the aging population of Newfoundland and Labrador? Canada?
My research will benefit the province by providing the foundation for future research to build upon. The only way we can treat the disease is if we can understand the underlying cause of the disease, and this starts at the molecular level. Understanding the proteins involved, what makes them dysfunctional, how they spread, and how that relates to the behavioural phenotypes observed will allow researchers to develop treatments for the disease.
ARC-NL: Is there any past experience you feel is pertinent to your success today?
My research career first began in 2016 when I volunteered in Dr. Christina Thorpe's lab studying circadian rhythms; this is where my passion for research began. Throughout the years, I have volunteered and worked in other labs, which have, without a doubt, had an impact on my success today. While I graduated with my master's in February 2021, all of the experiences and skills that I gained played a significant role in getting hired as Memorial's Animal Care Committee Coordinator. While I currently am not conducting any research of my own, I am still involved in the field in a different capacity.