Press Releases

HKUST Scientists Identify an Innovative Strategy Targeting a Blood Protein for Therapeutic Treatment of Alzheimer's Disease


25 August 2022












An international research team, led by Prof. Nancy IP, The Morningside Professor of Life Science at the Hong Kong University of Science and Technology (HKUST) and Director of the Hong Kong Center for Neurodegenerative Disease (HKCeND), has identified a blood protein that plays a key role in the pathogenesis of Alzheimer’s disease (AD). Their findings reveal an innovative strategy in reducing the risk of AD development and ameliorating disease pathologies in individuals living with AD.

AD, which affects over 50 million people worldwide, is currently an irreversible condition that lacks effective treatment. This is primarily because the disease mechanisms are complex and largely unclear, with few effective targets available for drug development. Researchers have previously observed that impaired clearance of the toxic amyloid-beta (Aβ) peptides in the brain of AD patients by the immune cells (microglia) causes cellular dysfunction, resulting in memory loss and cognitive problems. Yet, the reason behind this impairment is still not well known.

Now, the team has discovered a blood protein, soluble ST2 (sST2), that plays a key role in disrupting Aβ clearance by microglia. The team showed that sST2 levels increase in the blood and the brain during aging, thereby perturbing the activities of the cytokine interleukin-33 (IL-33), leading to reduced microglial clearance of Aβ and thus elevated Aβ deposition. The team had, in fact, previously discovered the beneficial activity of IL-33 on microglial clearance of Aβ in the brain. Interestingly, they further found that reduced sST2 levels confer a protective effect against AD development, and ameliorate AD-related pathologies in individuals who have developed the disease.

The research team further discovered that sST2 levels are regulated by genetic factors. Individuals carrying a genetic variant termed “rs1921622” show comparatively low sST2 protein levels in the blood and the brain even when they age, and have a lower chance of developing AD. This is particularly evident in women carrying the APOE4 gene, the strongest genetic risk factor of AD. As revealed in postmortem brain studies by the team, carriers of this protective genetic variant displayed significantly alleviated AD-related pathologies, marked by lower Aβ plaque deposition, reflecting better Aβ clearance by microglia in the brain.

Taken together, these critical findings open up new possibilities for the therapeutic treatment of AD that are primarily aimed at decreasing sST2 levels. This innovative strategy only requires manipulation of the protein in the blood, and thus offers a simpler and safer approach compared to other therapeutic strategies that target the brain. Particularly, it gives hope to high-risk groups such as female APOE4 carriers, who tend to bear a higher risk of AD development and exhibit more severe symptoms after developing the disease, accounting for 25% - 50% of all AD patients.




“While this exciting work has further improved our understanding of AD, and identified an excellent drug target for developing therapeutics, it has also made clear the importance of precision medicine in tackling this complex, multi-factorial disease,” said Prof Ip. “The next step is to develop clinical interventions that target sST2 and determine their viability as effective AD preventatives and treatments, especially for female APOE4 carriers who are at high risk of developing AD.”

The work was conducted with the support from the InnoHK scheme of the HKSAR government and undertaken in collaboration with researchers at University College London and Stanford University, clinicians at the Prince of Wales Hospital, the University of Melbourne, and Edith Cowan University. The results were recently published in the prestigious journal Nature Aging, and have also been featured and actively discussed on various scholarly exchange platforms focused on AD research such as Alzforum.

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President Xi Visits HKUST’s Hong Kong Center for Neurodegenerative Diseases


1 July 2022

President Xi Jinping made an official visit to the Hong Kong Center for Neurodegenerative Diseases (HKCeND) at the Hong Kong Science and Technology Park yesterday in the company of officials from the Central Government and the HKSAR Government. Prof. Nancy IP, Director of HKCeND and The Morningside Professor of Life Science at The Hong Kong University of Science and Technology (HKUST), introduced President Xi to the key research projects and outcomes of the Center, including a simple blood test for early detection and classification of Alzheimer’s disease (AD) and related stem cell research.










Established in 2020 with an initial funding of HK$500 million from the HKSAR Government’s InnoHK Clusters initiative, the HKCeND is a world-leading research center dedicated to neurodegenerative disease research and knowledge transfer. President Xi expressed keen interest in the AD research projects conducted by HKCeND scientists, and inquired in detail about the research progress, associated technical advantages, and future clinical applications.

"I am very honored in receiving President Xi,” said Prof. Ip, adding that President Xi attaches great importance to Hong Kong’s innovation and technology (I&T) development and progress. "It is estimated that China currently has 10 million AD patients, the highest prevalence in the world, and this number is expected to grow further with an ageing population. It is foreseeable that this disease will impose a great impact on the country’s social and economic development. President Xi both recognized our research results and lauded the significance of our work. He also encouraged us to strengthen collaborations with institutes and universities in the Mainland, and translate our research findings into therapeutic applications to benefit society."

Prof. Ip added, “The researchers at our Center feel very honored and inspired by President Xi’s visit. We are galvanized by his support and will expedite the translation of our scientific research to proactively take part in the country’s science and technology development.”

Before concluding the visit, President Xi addressed more than 30 representatives of Hong Kong scientific researchers and young entrepreneurs and encouraged them to make greater contributions to show his care for Hong Kong's youth in particular. The address demonstrated the importance and acknowledgement placed on Hong Kong's I&T development and the expectation of Hong Kong contributing to the country's development in science and technology.

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HKUST Pushes Forward Research on Early Diagnostics and Gene Therapy for Neurodegenerative Diseases


11 May 2022


Researchers at the Hong Kong Center for Neurodegenerative Diseases (HKCeND), founded by The Hong Kong University of Science and Technology (HKUST), have made promising breakthroughs in early diagnosis and therapeutic treatment of Alzheimer’s disease (AD) that have the potential to transform disease management. The team has established advanced biomarker discovery platforms, identified new blood-based biomarkers, and created an innovative artificial intelligence-based scoring system that enable risk prediction, early detection, and classification of AD. Furthermore, the team has also successfully developed a gene therapy strategy as a novel therapeutic treatment for AD.


Established in 2020 with an initial funding of HK$503.5 million from the Hong Kong government’s InnoHK Clusters initiative, HKCeND aims to be the world’s leading research center focused on neurodegenerative diseases. The Center has forged strategic collaborations with research investigators from Stanford University School of Medicine and University College London, with the goal of developing novel biomarkers and identifying therapeutic targets and systemic factors to treat neurodegenerative diseases.

AD, the most common form of dementia, is a devastating and incurable neurodegenerative disease that affects more than 50 million people globally. Treating AD remains a significant challenge since diagnostic methods primarily detect the disease at its advanced stage - after clinical symptoms such as memory loss appear. Given that disease onset is at least 10-20 years prior to the appearance of symptoms, early diagnosis of AD is the key to effective treatment. Early detection of AD, when it manifests as mild cognitive impairment or early dementia, would enable timely management/ therapeutic intervention resulting in improved outcomes. Biomarkers associated with early stages of AD have been found to have important applications in early diagnosis.


HKCeND researchers have extensive expertise in biomarker research. Previous achievements include conducting the first whole genome sequencing study of AD in the Chinese population and establishing the first comprehensive Chinese AD genetic database, resulting in the identification of AD genetic risk factors. These accomplishments have led to the development and establishment of novel and robust biomarker platforms at the HKCeND. Furthermore, by leveraging their genetic studies on Chinese AD patients and utilizing artificial intelligence tools, the team has developed the first deep learning-based polygenic risk scoring system that enables objective assessment of AD risk.

The team has also identified blood-based protein biomarkers and is developing a customized panel of AD blood protein biomarkers that can accurately classify patients with AD and evaluate disease status from a single drop of blood. This technology can be applied towards developing a clinical tool to efficiently and effectively diagnose AD at an early stage and for disease stratification. Given the clinical value of such tests, the team is actively pursuing commercialization opportunities with strategic industry partners. Collectively, these successes are increasing the HKCeND’s stature as the preeminent center for advanced biomarker research and laying a solid foundation for the development of precision diagnosis.


Concurrent to their biomarker research, the HKCeND team is also focused on developing new therapeutic approaches for AD, in particular, gene therapy. Gene therapy has not been considered a promising therapeutic approach for brain diseases such as AD due to the lack of an effective and non-invasive delivery tool capable of crossing the blood-brain-barrier. Recently, the team generated the first engineered delivery vehicle and demonstrated its ability to not only effectively cross the blood-brain-barrier but also deliver a genome-editing tool to the entire brain through a single non-invasive intravenous administration. Using this system, the team successfully disrupted AD-associated mutations and alleviated AD pathologies in the entire brain of AD mouse models. This work is an important milestone in the development of new disease-modifying therapies.


“Together with our collaborators from different parts of the world, we are drawing leading scientists in the field to conduct pioneering research at the Center. The InnoHK initiative provides an important platform for the Center to facilitate multi-disciplinary and cross-institutional collaborations to further advance knowledge for early detection and therapeutic treatment of AD,” said Prof. Nancy Ip, Director of HKCeND and The Morningside Professor of Life Science at HKUST.


“We are confident that the Center will play a leading role in advancing research in neurodegenerative diseases, from talent development to conducting world-class research, to accelerate the development of precision diagnosis and medicine that will benefit millions of people globally,” Prof Ip added.


The research work of the Center is led by eminent scientists and brings together more than 60 researchers from all over the world. The Center is looking for research talents to join the fast-growing team, committed to nurturing a new generation of innovation and technology (I&T) talent.