Dr. Printha Wijesinghe on tear-based microRNAs as early indicators of Alzheimer’s disease

An academic journey defined by perseverance through conflict and limited opportunity – Dr. Printha Wijesinghe’s path to neuroscience is anything but ordinary.

Dr. Printha at the dissection microscope

Born in Jaffna, Sri Lanka, Dr. Printha grew up in an environment shaped by prolonged civil war and riddled with severe disruptions to education and stability. Though she originally dreamed of becoming a doctor, the challenges she faced led her down a different path. She went on to study agriculture and graduated at the top of her class.  

Afterwards, she moved to Colombo to pursue a Master’s in Biochemistry, Molecular Biology, and Gene Technology. Unable to return to her hometown due to the ongoing war, she accepted a research assistant position in neurogenetics under Dr. Ranil de Silva. Despite limited resources and a high-pressure environment, it was here that she discovered her passion for neuroscience. One opportunity led to another: a nomination to a regional neuroscience school, helping to establish Sri Lanka’s first human brain bank and eventually a fellowship in neuropathology in India. This work formed the basis of a dual PhD program between the University of Sri Jayewardenepura and Maastricht University. 

But after immigrating to Canada, she found herself starting over once again—this time while caring for a newborn and managing family responsibilities. 

“Just when I was close to giving up, I received an opportunity from Dr. Desmond Nunez at UBC,” she recalls.  

Over the next four years, Dr. Printha transitioned into hearing research, a field entirely new to her. She coordinated clinical trials, conducted primary cell cultures and studied the molecular signatures of sudden hearing loss, contributing to ten publications—two as first author. When COVID-19 funding cuts reduced her hours, she saw it as a chance to return to her original passion: Alzheimer’s disease. 

A personal and scientific calling 

Dr. Printha’s interest in Alzheimer’s disease (AD) is both personal and professional. 

“In my home country of Sri Lanka, dementia and cognitive impairments are often overlooked as inevitable aspects of aging,” she says. “They’re often overshadowed by more immediate health concerns such as cardiovascular disease, diabetes and stroke, compounded further by social and racial disparities.”  

Her formal training in AD began during her PhD, studying brain tissue in Sri Lanka’s first human brain bank. Later, as a neuropathology fellow at the National Institute of Mental Health and Neurosciences in India, she conducted detailed analyses of elderly brain samples from Sri Lanka and India, using established AD scoring systems. 

She was struck by what she found: a surprisingly high prevalence of Alzheimer’s-related pathology in the Sri Lankan cohort. Was it related to differences in life expectancy? Could underdiagnosed neurodegenerative disease be part of the picture?  

“This hands-on experience sparked a deep interest in the biology of aging,” she says. 

Building on these findings, she expanded her research to explore vascular contributions to dementia through her dual doctoral program.  

Eyes on the brain 

Dr. Printha and the Matsubara lab

In 2021, Dr. Printha joined the lab of Dr. Joanne Matsubara at UBC as a postdoctoral fellow, officially returning to Alzheimer’s research. This time, her work investigated an unconventional source of early biomarkers: tears. 

“The eye is often called a window to the brain,” she explains, “because of the anatomical and functional continuity between the retina and central nervous system.” 

While cerebrospinal fluid (CSF) can offer insight into brain changes, the procedures required to collect it can be invasive and risky. Tear fluid, on the other hand, also comes from the central nervous system, but is much easier to collect, non-invasive, and, like CSF, is clear and protein rich.  

“Importantly, tear fluid has been shown to reflect central nervous system alterations,” she says. “Its potential as a biomarker source for Alzheimer’s disease is increasingly supported by emerging evidence.”  

What are microRNAs?  

Although the human genome is vast, only about 1 per cent codes for proteins. The rest, once thought of as “junk,” actually includes powerful regulatory molecules such as microRNAs (miRNAs). 

“These are very small pieces of RNA—just about 20 to 22 building blocks long,” Dr. Printha explains. “Even though they don’t make proteins themselves, miRNAs play a powerful role —they help control which proteins get made in our cells by interfering with the messages that direct protein production.”  

Interestingly, miRNAs can circulate in bodily fluids such as blood, saliva and tears. Their stability and abundance in these fluids make them especially useful as disease biomarkers. Researchers are increasingly investigating them for early detection of conditions like cancer, cardiovascular disease and Alzheimer’s. 

Detecting Alzheimer’s disease earlier   

Alzheimer’s is marked by sticky amyloid plaques and twisted tau tangles that gradually kill brain cells. Most cases arise from a mix of genetic and environmental factors rather than a single mutation, making the disease difficult to detect and treat early.  

Because of this complexity, targeting a single molecule or pathway has proven scientifically rigorous but has not led to effective treatments—one of the key reasons a cure remains elusive. 

Dr. Printha says that microRNAs offer a broader and more integrative approach to understanding how disease develops.  

“These small, non-coding RNAs regulate many target genes at once,” she explains. “Screening panels of miRNAs involved in processes like amyloid buildup, inflammation and tau-related changes may offer deeper insights into how Alzheimer’s progresses.”  

Using a mouse model of Alzheimer’s, she studied miRNA levels in brain, eye and tear tissues at different disease stages. She discovered that certain miRNAs linked to amyloid buildup, inflammation and tau changes were consistently lower in diseased animals. Tear samples mirrored the brain’s miRNA profiles—a striking connection. A small pilot study involving patients with mild cognitive impairment and early-stage Alzheimer’s showed similar patterns.  

“While these findings are encouraging,” she says. “Larger studies are needed to determine their clinical utility as diagnostic biomarkers.” 

Looking ahead 

Dr. Printha with her poster at the AAIC 2025 conference on July 29, 2025, in Toronto, Canada.

Supported by Postdoctoral Fellowships from the Alzheimer Society Research Program, Michael Smith Health Research BC and Canadians for Leading Edge Alzheimer Research (CLEAR) Foundation, Dr. Printha is advancing her investigation of tear-based microRNA biomarkers in both human participants and transgenic mouse models. Through comprehensive analysis of brain and eye tissue from multiple mouse strains and non-carrier sibling controls, she is working to uncover the molecular and pathological mechanisms that distinguish familial from sporadic forms of the disease.  

Her research also sheds light on sex-based differences in vulnerability to Alzheimer’s, with a particular focus on the increased risk observed in females. 

From navigating a war-affected education system to earning dual PhDs, building Sri Lanka’s first human brain bank and rebuilding her career in Canada, Dr. Printha’s experiences have shaped her as both a scientist and mentor. 

“I am dedicated to upholding the values of inclusion, mentorship and scientific excellence—principles that were not always extended to me,” she states. “With continued recognition and support in Canada, I hope to expand my research on Alzheimer’s, related dementias and retinal neurodegeneration, ultimately helping to transform how we treat these diseases.”  

Outside the lab, she enjoys cooking healthy meals for her family, watching comedies, and listening to music and motivational talks, simple joys that help her relax and recharge.