Neuroscientist Explores Potential Link Between Immune Response and Alzheimer’s
HKUMed neuroscientist Professor Raymond Chang has been appointed Bingei and L & T Charitable Foundation Professor in Dementia Research, in an award set to boost his research into the causes of Alzheimer’s.
Endowed Professorships are one of the most significant awards given to leading academics at the University of Hong Kong. These Professorships are named in honour of a donor or a corporation or other honoree recommended by the donor. Since their establishment in 2005, 120 Endowed Professorships have been awarded to scholars.
In celebration of the Medical Faculty’s newly appointed Endowed Professors, we sat down with them to discover more about their careers and their research goals.
Professor Raymond Chang from the School of Biomedical Sciences was awarded the newly created Bingei and L & T Charitable Foundation Professorship in Dementia Research in late 2024.
“I sincerely thank the Bingei family and the L&T Charitable Foundation for establishing this Professorship for Dementia Research that will allow us to further enhance our research,” Professor Chang said, expressing his gratitude to the donors, Dr Rita Tong Liu and family.
He explained that the endowment will help fund the exploration of risk factors behind Alzheimer’s, a type of dementia that affects an estimated 55 million people worldwide.
Alzheimer’s mostly affects people over the age of 65, making the urgency for research into this disease particularly great in ageing societies like Hong Kong and China. Hong Kong is set to become an ultra-aged society by 2034 with 28% of the population over 65.
Professor Chang grew up in Hong Kong and completed a PhD in Munich before joining the National Institute for Health in the United States. He joined HKUMed in 2000.
He was first drawn to studying neuroscience after his undergraduate classes highlighted how little was known about the human brain. At the time, scientists were yet to pinpoint the cause of tremors in Parkinson’s patients or to discover how we learn.
In his role at HKUMed, he researches neuroscience and neuroimmunology, a multidisciplinary subject that combines immunology and neuroscience.
This area of research is now also deeply personal. Professor Chang’s mother was diagnosed with Alzheimer’s and his father with Parkinson’s in later life. His pursuit of these diseases in the laboratory had not prepared him to care for loved ones as their quality of life declined. This experience taught him that his work is valuable for potential drug development for patients and for reducing the pressure placed on family members.
‘A little breakthrough’
Originally focusing on the signalling mechanisms and degeneration of neurons in Alzheimer’s, Professor Chang is now also examining the risk factors behind neurodegenerative diseases.
One promising area of study is how the brain is affected by the body’s response to infections and injury.
The body and the brain have separate cell types for immune response. The body relies on cells such as B cells, T cells and macrophages to fight infection. Separately, the brain relies on one type of cell called microglia.
Previously, it was thought the blood-brain barrier blocked the body’s immune cells from entering the brain. It has now been found that macrophages can cross into the brain where they secrete cytokines, small proteins that aid cell signalling and immune response.
“The original purpose [of the cells] is good, but when at a high level in the brain… that facilitates the degeneration of neurons,” Professor Chang said.
The neuroscientist’s laboratory has pinpointed Interleukin 34 (IL-34), a type of cytokine, for further research.
“We now have a little bit of a breakthrough. We’ve now found out in what kinds of situations those immune cells, macrophages, can interact with the brain endothelial cells,” Professor Chang said, referring to the blood-brain barrier. “When they interact with the barrier then they actually find a way to squeeze into the brain and then secrete more inflammatory factors.”
His team identified that IL-34 is important in controlling how macrophages enter the brain. They are now working to understand its full role.
Zebrafish, a tiny type of fish with transparent bodies and similar immune cells and brain structure to humans, are vital to this research. The research team uses transgenic zebrafish that produce fluorescent green macrophages, allowing the scientists to visually track the movement of the immune cells in the fish.
“First, we want to understand in what kind of situations macrophages go to the brain. Second is why they go to the brain and third is how they go to the brain.” he said. “And the last question we ask is what are the consequences of [these cells] going into the brain.”
This line of research is expensive as Professor Chang’s laboratory must cover the cost of keeping a zebrafish colony and buy pricy reagents. Funds from the Endowed Professorship will greatly aid in meeting these costs and furthering this research, the neuroscientist said.
From benchside to bedside
As Professor Chang plans how this award will help advance his Alzheimer’s research, he is also keen to see his existing findings applied outside the laboratory.
His findings made in collaboration with anaesthesiologists, ophthalmologists and dentists, have led him to conclude that multiple factors can lead to Alzheimer’s disease. This offers an opportunity for clinicians to actively assess the impact on the brain of common illnesses.
“We hope that our [studies] can eventually inform different disciplines of medicine that they need to collaborate with neurology to further monitor the brain,” he said.
