JoAnne McLaurin

Dr. McLaurin is Senior Scientist in Biological Sciences at Sunnybrook Research Institute, Professor in the Department of Laboratory Medicine and Pathobiology at University of Toronto, and holds a CRC Tier 1 Chair in Alzheimer’s disease Therapeutics.  

Dr. McLaurin is a member of the Research Executive Committee serving as the Co-lead of  Preclinical Research within the Canadian Consortium on Neurodegeneration and Aging, a Canada-wide initiative to expedite the development of new therapies for neurodegeneration. She has also served as the preclinical co-lead for the Vascular Cognitive Impairment team within the Canadian Consortium on Neurodegeneration and Aging (CCNA). She is actively involved in the Toronto Dementia Research Alliance.

Dr. McLaurin’s international reputation has led to her serving on multiple international grant review panels, site visits and consultations to industry. Dr. McLaurin served as chair and a reviewer on NIH Drug Discovery for the CNS grant review panel and international review panels including DFG, German Research Foundation, Swiss National Research Foundation, Alzheimer’s Association US, and The Israeli Science Foundation.   

She continues to engage as much as possible in outreach programs to mentor students and advocate for STEM programs. Dr. McLaurin works with community groups to promote understanding of Alzheimer’s disease, dementia and to emphasize lifestyle choices that can have beneficial effects on the long-term risk of developing these diseases.

Research Synopsis

My team’s research has focused on development of potential therapeutics to target protein-misfolding disorders, in particular Alzheimer’s disease (AD). Immunization is the most active area of drug development in AD and my laboratory has contributed significantly to this work. Therapeutic trials of Aβ-immunization in humans are hindered by the occurrence of ARIA, a cellular inflammatory reaction. My work demonstrated that beneficial effects in mice arise from antibodies selectively directed against residues 4-10 of  Aβ42, that inhibit Aβ ibrillogenesis and cytotoxicity without eliciting an inflammatory response. This knowledge provided the basis both for improved immunization antigens, and for attempts to design small molecule mimics as alternative therapies. 

In light of this, my laboratory identified a family of naturally occurring compounds that inhibit the formation of toxic soluble aggregates in AD, which resulted in worldwide patents and collaborations with small cap biotechnology and large pharmaceutical industry. Preclinical studies in my laboratory demonstrated efficacy, subsequent early clinical trials in AD patients were initiated but unsuccessful. However, this just drives our research further to develop new strategies to treat Alzheimer’s disease and age-related dementia. Our endeavors include characterization of novel therapeutics that might be used in combination with small molecule therapies to fully recover functioning in Alzheimer’s disease.  

This work is based on the premise that strategies in clinical trials to date will have some beneficial effects in stabilizing disease progression, yet to achieve optimal cognitive functioning combination therapies that address other targets will be necessary. Our work is investigating the role of aging in neurodegeneration and the age-specific factors, which leads to susceptibility to injury/dementia within the CNS. These include life-style choices and co-morbid diseases such as metabolic syndrome, hypertension and covid strokes that increase risk of developing dementia with aging.
My team’s successful research program demonstrates our ability to identify target molecules, to develop lead compounds through preclinical development and to translate this knowledge to appropriate international stakeholders. 

Selected Publications

Lai, A.Y., Joo, I.L., Trivedi, A.U., Dorr, A., Hill, M.E., Stefanovic, B., McLaurin, J., Transient hypertension promotes different profiles of cerebrovascular remodeling in a rat model of normal aging and Alzheimer’s disease. Brain Res, 1758:147369, 2021.

Liu, M., Beckett, T., Thomason, L.A.M., Dorr, A., Stefanovic, B., McLaurin, J. Covert strokes prior to Alzheimer’s disease onset accelerate peri-lesional pathology but not cognitive deficits in an inducible APP mouse model. Brain Res, 1754:147233, 2021.

Morrone, C.D., Bazzigaluppi, P., Beckett, T.L., Hill, M.E., Koletar, M.M.,  Stefanovic, B. and McLaurin, J.  Regional differences in Alzheimer’s disease pathology confound behavioural rescue after Aβ attenuation. Brain 143, 359–373, 2020.

Bazzigaluppi, P., Beckett, T., Koletar, M.M., Hill, M.E., Lai, A.Y., Trivedi, A.U., Thomason, L.A.M., Dorr, A., Gallagher, D., Librach, C., Joo, I.L., McLaurin, J., Stefanovic, B. Combinatorial treatment using umbilical cord perivascular cells and Aβ clearance rescues vascular function following transient hypertension in a rat model of Alzheimer’s Disease. Hypertension, 74:1041–1051, 2019.

Jevtic, S., Sengar, A.S., Salter, M.W., McLaurin, J., The Role of the Immune System in Alzheimer Disease: Etiology and Treatment. Ageing Research Reviews, 40, 84-94, 2017.

Morrone, C.D., Thomason, L.A.M., Brown, M.E., Aubert, I., McLaurin, J., Effects of Neurotrophic Support and Amyloid-Targeted Combined Therapy on Adult Hippocampal Neurogenesis in a Transgenic Model of Alzheimer's Disease. PLoS One 2016; 11:e0165393.

Lai, A., Dorr, A., Thomason, L.A.M., Sled, J., Stefanovic, B., McLaurin, J. Venular mural cells are important regulators of global vascular function in cerebral amyloid angiopathy. Brain 138, 1046-1058, 2015.

Honours and Awards

Canada Research Chair (CRC) Tier 1 Chair in Alzheimer’s disease Therapeutics