November 30, 2023 by LIFS Editor News 0 comments

VCAM1: A Promising Therapeutic Target for Alzheimer’s Disease

HKUST President Prof. Nancy IP (center, front row), Research Professor Prof. Amy FU (second right, front row), a co-first author of this research paper Mr. WU Wei (second left, front row), and Research Assistant Professor Prof. WONG Hiu Yi (first left, front row) with other members of the HKUST Division of Life Science research team.

Dr. LAU Shun-Fat, a co-first author of this research paper and former Postdoctoral Fellow at HKUST Division of Life Science, is now a Postdoctoral Associate at the Yale University School of Medicine.

The diagram illustrates the VCAM1-APOE signalling pathway as a potential therapeutic target for Alzheimer’s disease. Interleukin-33 (IL-33) (1) increases VCAM1 expression in microglia (2), which stimulates the attraction of microglia to APOE-associated amyloid-β (Aβ) deposition (3), leading to the clearance of Aβ in the brain (4).

A research team led by Prof. Nancy IP the President and The Morningside Professor of Life Science at The Hong Kong University of Science and Technology (HKUST), and the Director of the Hong Kong Center for Neurodegenerative Diseases (HKCeND) has identified VCAM1, a cell surface protein present on brain immune cells, as a promising target for Alzheimer’s disease (AD) treatment. AD is a devastating neurodegenerative disorder characterized by the accumulation of amyloid-beta (Aβ) plaques in the brain, leading to cognitive decline. Microglia, brain-resident immune cells, play a crucial role in clearing Aβ plaques but become dysfunctional in AD.

The team discovered that VCAM1 on microglia facilitates their migration towards Aβ plaques and promotes Aβ clearance. They also found that APOE, a protein found in Aβ plaques, works together with VCAM1 to mobilize microglia to the plaques. Stimulating the “VCAM1-APOE” pathway reduced AD pathology in a mouse model. Additionally, AD patients exhibited elevated levels of soluble VCAM1 in their cerebrospinal fluid, indicating dysregulated VCAM1-APOE signaling and impaired Aβ clearance by microglia.

These findings highlight the importance of VCAM1-APOE signaling in AD pathogenesis and propose VCAM1 as a promising target for therapeutic interventions. Prof. Nancy Ip expressed the significance of these discoveries in expanding our understanding of the disease and emphasized the need to identify appropriate drug targets for effective AD treatment. The research team aims to continue their innovative approaches in pursuit of this goal.

https://hkust.edu.hk/news/research-and-innovation/hkust-scientists-unveil-promising-target-alzheimers-disease-treatment

Journal Reference:

Shun-Fat Lau, Wei Wu, Hiu Yi Wong, Li Ouyang, Yi Qiao, Jiahui Xu, Jessica Hiu-Yan Lau, Carlton Wong, Yuanbing Jiang, David M Holtzman, Amy K Y Fu, Nancy Y Ip. The VCAM1-ApoE pathway directs microglial chemotaxis and alleviates Alzheimer’s disease pathology.

Nat Aging 2023 Oct;3(10):1219-1236. doi: 10.1038/s43587-023-00491-1.

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VCAM1: A Promising Therapeutic Target for Alzheimer’s Disease

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