HKUST scientists find promising target for Alzheimer’s disease treatment
A research team led by Prof. Nancy Ip, the President and Morningside Professor of Life Science at the Hong Kong University of Science and Technology, and the Director of the Hong Kong Center for Neurodegenerative Diseases, has identified VCAM1, a cell surface protein found on immune cells of the brain, as a therapeutic target for Alzheimer’s disease, paving the way for developing novel therapeutics to combat this debilitating condition.
Alzheimer’s disease is a devastating neurodegenerative disorder that affects over 50 million people worldwide. A key pathological hallmark of the disease is the accumulation of amyloid-beta plaques in the brain, which leads to progressive decline in cognitive function. Microglia, resident immune cells of the brain, are thought to play a vital role in the clearance of amyloid-beta plaques, a function that is impaired in Alzheimer’s disease.
The research team sought to investigate how microglia control amyloid-beta clearance and how they become dysfunctional in Alzheimer’s disease. Through their study, the team discovered that VCAM1, a cell surface protein on microglia, mediates microglial migration towards amyloid-beta and promotes microglial clearance of amyloid-beta. The team also discovered that another protein found in amyloid-beta plaques, APOE, acts in conjunction with VCAM1 to mobilize microglia to amyloid-beta plaques. The team further found that stimulating the “VCAM1–APOE” pathway reduced Alzheimer’s disease pathology in a mouse model of Alzheimer’s disease. These findings suggest that proper VCAM1 functioning is critical for microglial migration and clearance of amyloid-beta.
The team also examined VCAM1-expressing microglia in the brain tissue of Alzheimer’s disease patients. Interestingly, Alzheimer’s disease patients exhibited elevated levels of soluble VCAM1 in the cerebrospinal fluid, which suggested dysregulated VCAM1-APOE signaling. This observation correlates with reduced clearance of amyloid-beta by microglia.
Collectively, the findings of the study implicate VCAM1–APOE signaling in the pathogenesis of Alzheimer’s disease and identify VCAM1 as a promising target for Alzheimer’s disease therapy. The results were published in Nature Aging.
“These exciting findings have not only expanded our understanding of the disease pathology, but also unveiled a new target for developing disease interventions.” said Prof. Nancy Ip. “While there is an urgent need for effective disease-modifying treatments, we need to first identify the right drug targets. We will continue our efforts using innovative approaches towards this goal.”
