An international research team led by the Hong Kong University of Science and Technology (HKUST) has identified key genetic factors that confer protective effects against Alzheimer’s disease (AD) through a comprehensive genetic analysis of East Asian populations, including Chinese and Japanese, as well as European populations. This groundbreaking discovery sheds light on how these genetic factors can exert protective effects, unveiling the biological mechanisms underlying AD pathogenesis. At a glance: Discovery: An AD-protective genetic variant, Hap_A of SORL1, was identified. Its prevalence in East Asians, including Chinese and Japanese, is 168 times that of Europeans. Evidence: Hap_A was proven to be associated with better cognitive performance and is linked to increased human tissue expression of SORL1, an important receptor in AD. Significance: This study showcased how genetic studies in different populations could help unravel the effects of genetic factors on AD. A specific coding variant of a novel SORL1 protein isoform was discovered and could be a promising target for further mechanistic studies of the disease. Affecting over 50 million people worldwide, AD is a devastating neurodegenerative disorder that imposes a substantial socioeconomic burden. However, effective treatments remain limited due to the complex mechanisms of the disease and the few effective targets for drug development. In the past decade, research into the SORL1 gene (Sortilin-Related Receptor 1) has gained attention in the field of AD, as the protein it encodes, SORL1, plays a crucial role in regulating the production and clearance of amyloid-beta, a toxic protein that contributes to the pathology of AD. Studies conducted in individuals of European descent have suggested that certain SORL1 genetic variants exert protective effects against AD, making it a potential target for disease intervention. However, most genetic studies have mainly focused on the European population, leaving gaps in understanding how SORL1 variants affect other ethnic groups. Therefore, investigating SORL1 genetic variants in the East Asian population will provide new insights into how these variants may exert protection against AD. This highlights the importance of comprehensive research that includes diverse ethnic groups to enhance our understanding of how ancestral backgrounds influence the genetic mechanisms underlying the disease. To investigate how SORL1 genetic variants protect against AD in diverse populations, a multidisciplinary team led by Prof. Nancy IP, President and the Morningside Professor of Life Science at HKUST and Director of the Hong Kong Center for Neurodegenerative Diseases (HKCeND), performed a comprehensive genetic association analysis across East Asian populations, including individuals from mainland China, Hong Kong, and Japan, as well as European populations. This research was conducted in collaboration with Prof. John Hardy from University College London, Prof. Akinori Miyashita from Niigata University, and Prof. Yu Chen from the Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, while also integrating data from international databases, including the Alzheimer’s Disease Neuroimaging Initiative. The team identified key SORL1 genetic variants in both East Asian and European populations. In particular, the Hap_A variant showed a strong protective effect against AD in the East Asian population, while it is relatively rare in the European population. The prevalence of Hap_A in East Asians is 168 times that of Europeans. Their analysis revealed that individuals carrying the Hap_A variant had better cognitive function, decreased neurodegeneration, and less severe AD pathology when compared with those not carrying the variant. Their findings demonstrated that different ethnic groups exhibit distinct sets of variants that exert AD-protective roles. To further understand the biological mechanisms of these AD-protective SORL1 genetic variants, the team comprehensively examined the functional roles of the variants. Their results showed that the AD-protective genetic variants are associated with increased SORL1 protein expression and may modulate biological pathways related to both immune and neuronal functions. Notably, the team identified a specific coding variant that regulates the expression and function of a SORL1 protein isoform, which had not been comprehensively studied previously. This finding provides new insights into the molecular mechanism underlying how SORL1 protein modulates AD risk. “This study enhances our understanding of the role of SORL1 in AD and has uncovered its potential for therapeutic development,” said Prof. Ip. “Our research, built on international collaboration, contributes to one of the most comprehensive East Asian human databases for AD, serving as a valuable resource for studies of AD genetic factors in diverse ethnic populations.” The research was supported by the National Natural Science Foundation of China (NSFC) and the Research Grants Council (RGC) of Hong Kong Joint Research Scheme and the InnoHK scheme of the HKSAR government. It was conducted in collaboration with researchers from University College London and Niigata University, as well as clinicians from the Prince of Wales Hospital and Queen Elizabeth Hospital. The findings have been recently published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, and featured on Alzforum, a scholarly exchange platform focused on AD research.

Hong Kong Center for Neurodegenerative Diseases (HKCeND) has received 3 prestigious awards at the International Exhibition of Inventions Geneva 2024. These accolades highlight the groundbreaking innovations showcased by the HKCeND team, aimed at addressing the pressing medical challenges posed by Alzheimer’s disease (AD). One of the award-winning inventions introduces an innovative strategy targeting soluble ST2 (sST2), a blood protein, for the development of AD therapeutics. This research has won the Prize of the Chinese Delegation for Invention and Innovation, as well as the Gold Medal with Congratulations of the Jury. The research findings have unlocked new possibilities for the development of AD therapeutics. Therapeutics targeting sST2 can reduce the risk of AD development and ameliorate associated pathologies. Importantly, these therapeutic approaches offer a simpler, less invasive, and safer option compared to traditional AD treatment approaches. Moreover, the non-invasive brain-wide genome editing approach for treating familial Alzheimer’s disease (FAD), has garnered a Gold Medal. This revolutionary invention is a universal approach capable of correcting specific genetic mutations in individual patients, thereby alleviating the pathologies associated with FAD. The technology offers immense potential to revolutionize treatments of familial diseases. HKCeND Center Director, Prof. Nancy IP said, “We are honoured to receive global recognition for our scientific breakthroughs. Through collaborations with academia, research and medical institutes, industry partners, as well as the government, we remain dedicated to translating our research innovations into practical solutions that benefit society.’ The International Exhibition of Inventions Geneva is one of the largest annual global events devoted exclusively to inventions. This year, the exhibition showcased 1,035 inventions from 38 countries and regions.

An HKUST-led international research collaboration has achieved a significant milestone in Alzheimer’s disease (AD) diagnosis and management. The team, spearheaded by Prof. Nancy IP, President and 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 Diseases (HKCeND), has developed a cutting-edge blood test for the early detection of AD and mild cognitive impairment (MCI), surpassing remarkable accuracy rates of over 96% and 87% respectively. Notably, this blood test is applicable across ethnic populations, providing a global solution to the diagnosis and management of AD. At a glance: Remarkably high accuracy rate – over 96% for AD and 87% for MCI; Applicable across diverse ethnic populations, including Chinese and European; Enables early detection of AD and subsequent progression; Captures multiple AD-associated biological pathways; A game-changer for AD diagnosis and precision treatment AD affects over 50 million people worldwide. A major hallmark of the disease is the accumulation of toxic amyloid beta (Aβ) in the brain, leading to the dysfunction and loss of brain cells, resulting in progressive memory loss, cognitive decline, and difficulties in daily tasks and communication. The recent approval of the AD drug Lecanemab offers new hope by targeting MCI or mild AD-related dementia with elevated Aβ in the brain. However, the majority of individuals with these conditions are undiagnosed and untreated, largely due to the challenges in making an early diagnosis. Currently, elevated Aβ can only be measured through costly brain imaging or invasive procedures. Additionally, disease diagnosis heavily relies on clinical observation of symptoms that typically appear 10-20 years after disease onset, by which time the disease has progressed to an advanced stage and is difficult to treat. Therefore, the development of a simple blood test that accurately identifies individuals with MCI and mild AD, while also detecting elevated Aβ in the brain, would be a game-changer for AD diagnosis and treatment strategies. Prof. Nancy IP and her team at HKUST have recently developed a blood test for the early detection of AD and MCI with exceptionally high accuracy. In a multinational study involving individuals of Chinese and European descent, the international research team demonstrated the robust performance of the blood test in distinguishing individuals with AD and MCI from cognitively normal people, as well as its ability to detect brain amyloid pathology. These findings also highlight the applicability of the test across diverse ethnic and regional boundaries, showcasing its potential for global impact. Furthermore, unlike existing blood assays that mainly focus on a single biomarker analysis to reveal brain pathology, the HKUST-developed blood test simultaneously measures the levels of 21 proteins, thus revealing the alterations in multiple crucial biological pathways, and achieving more accurate classification of AD and MCI as well as close monitoring of disease progression. This comprehensive AD profile for each individual opens the door for the future development of tailored treatment approaches for individual patients, known as precision medicine, which can revolutionize the field of AD diagnosis and management. ’Our blood test heralds a new era of simple, effective, and less invasive diagnostics, and by expanding the scope of our research to include diverse populations, we have taken a crucial step towards making our test a universally applicable tool for AD diagnosis,’ remarked Prof. IP. ’Our test can also be used to screen suitable individuals for specific drug treatments in clinical studies, and closely monitor disease progression and drug responses. In the future, it may also facilitate the development of personalized treatments, by shedding light on the molecular underpinnings of AD that vary from person to person and between ethnicities.’ The research was conducted in collaboration with researchers at University College London (London, UK) and the Barcelonaβeta Brain Research Center (Barcelona, Spain), as well as clinicians from local and overseas hospitals including the Prince of Wales Hospital (Hong Kong) and the Hospital del Mar (Barcelona, Spain). The work was recently published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association (https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/alz.13676) and has been licensed to a start-up company of HKUST, Cognitact Limited, to provide testing services to the public.

Hong Kong Center for Neurodegenerative Diseases (HKCeND) participated in the highly anticipated InnoHK Summit 2023, held at Hong Kong Science Park on 6 December 2023. Prof. Nancy Ip, Center Director of HKCeND, took the stage to share the groundbreaking research and development (R&D) breakthroughs in the field of Alzheimer’s disease. The inspiring presentation of Prof. Ip shed light on the key advancements of the Center in developing innovative diagnostic tests and therapeutic strategies, aimed at addressing the global health threat of Alzheimer’s disease, which is associated with an aging population. The interactive booths at the summit created a vibrant atmosphere, allowing the HKCeND team to engage in insightful exchanges and showcase their R&D achievements to visitors. ’This summit not only provided an exceptional platform for us to share our impactful R&D breakthroughs, but also facilitated us to exchange with world-class experts, innovators, and industry leaders. It further fuels our drive to revolutionize diagnostic and therapeutic solutions for Alzheimer’s disease,’ said Prof. Ip. As a research center under the InnoHK initiative, the Center remains committed to fostering global research collaboration, driving scientific and technological advancements, and translating R&D outcomes into tangible solutions. ’With a relentless pursuit of innovation and a top-notch team, we strive to bring impactful healthcare solutions that benefit society,’ added Prof. Ip. The InnoHK Summit 2023, organized by the Innovation and Technology Commission and the Hong Kong Science and Technology Parks Corporation, attracted more than 800 prominent academics, scientists, representatives of renowned institutes and industry leaders from Hong Kong and around the world. The summit showcased the latest innovations and developments of 28 InnoHK centers and unpacked innovation and technology (I&T) trends and opportunities through panel discussions with top experts from the industry and academia.

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 Center Director of the Hong Kong Center for Neurodegenerative Diseases (HKCeND), has identified VCAM1, a cell surface protein found on immune cells of the brain, as a therapeutic target for Alzheimer’s disease (AD), paving the way for developing novel therapeutics to combat this debilitating condition. AD 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 (Aβ) 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 Aβ plaques, a function that is impaired in AD. The research team sought to investigate how microglia control Aβ clearance and how they become dysfunctional in AD. Through their elegant study, the team discovered that VCAM1, a cell surface protein on microglia, mediates microglial migration towards Aβ and promotes microglial clearance of Aβ. The team also discovered that another protein found in Aβ plaques, APOE, acts in conjunction with VCAM1 to mobilize microglia to Aβ plaques. The team further found that stimulating the “VCAM1–APOE” pathway reduced AD pathology in a mouse model of AD. These findings suggest that proper VCAM1 functioning is critical for microglial migration and clearance of Aβ. The team also examined VCAM1-expressing microglia in the brain tissue of AD patients. Interestingly, AD patients exhibited elevated levels of soluble VCAM1 in the cerebrospinal fluid, which suggested dysregulated VCAM1-APOE signaling. This observation correlates with reduced clearance of Aβ by microglia. Collectively, the findings of the study implicate VCAM1–APOE signaling in the pathogenesis of AD and identify VCAM1 as a promising target for AD therapy. “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.”

Cognitact Limited – a biotechnology start-up from The Hong Kong University of Science and Technology (HKUST), has launched the PlasmarkADTM blood test service for early detection and staging of Alzheimer’s disease, which will revolutionize the diagnosis and treatment of Alzheimer’s and ultimately benefit society. The launch of PlasmarkAD marks a new milestone in the transformation and commercialization of innovation and technology targeting Alzheimer’s. Developed by a research team led by HKUST and licensed to Cognitact for further development and commercialization, the PlasmarkAD test provides a simple, non-invasive and accurate testing solution for Alzheimer’s disease through a single drop of blood. Leveraging cutting-edge blood protein biomarker detection technology and a self-developed machine learning algorithm, the test can detect the level changes of blood protein biomarkers, thus accurately distinguish patients with Alzheimer’s disease or mild cognitive impairment from cognitively normal people, and evaluate the instant status of different body systems for individuals. In current daily practice, Alzheimer’s disease is diagnosed clinically, mainly using medical history and cognitive tests. To aid in diagnosing Alzheimer’s disease, physicians could use brain imaging and cerebrospinal fluid test to detect pathological changes in the brain, but these methods are either expensive or invasive, and frequently unavailable in certain regions or countries. “Our PlasmarkAD test overcomes the above-mentioned limitations by allowing the general public to get a regular blood test for Alzheimer’s disease. This process is convenient, simple, and less invasive, making the early screening and monitoring of Alzheimer’s disease more accessible,” said Dr. Fanny Ip, Chief Scientific Officer of Hong Kong Center for Neurodegenerative Diseases (HKCeND) and Director of Cognitact. The PlasmarkAD blood test can diagnose Alzheimer’s disease 5-10 years before clinical symptoms manifest with over 96% accuracy, and also monitor the progression of the disease over time. Early detection of Alzheimer’s disease, can significantly assist clinical diagnosis and timely intervention, resulting in improved outcomes. ’We are proud to launch the PlasmarkAD blood test service, which represents a major step forward in the early detection of Alzheimer’s disease. We firmly believe that this will help better management of the disease and contribute to building a society that is more conducive to healthy aging,” added Dr. Ip. The PlasmarkAD test service is now available to the public in designated medical centres in Hong Kong. For more information about the solution, please visit the Cognitact website.

An international research team led by the Hong Kong University of Science and Technology (HKUST) has developed an artificial intelligence (AI)-based model that uses genetic information to predict an individual’s risk of developing Alzheimer’s disease (AD) well before symptoms occur. This groundbreaking study paves the way for using deep learning methods to predict the risks of diseases and uncover their molecular mechanisms; this could revolutionize the diagnosis of, interventions for, and clinical research on AD and other common diseases such as cardiovascular diseases. Researchers led by HKUST’s President, Prof. Nancy IP, in collaboration with the Chair Professor and Director of HKUST’s Big Data Institute, Prof. CHEN Lei, investigated whether AI—specifically deep learning models—can model AD risk using genetic information. The team established one of the first deep learning models for estimating AD polygenic risks in both European-descent and Chinese populations. Compared to other models, these deep learning models more accurately classify patients with AD and stratify individuals into distinct groups based on disease risks associated with alterations of various biological processes. In current daily practice, AD is diagnosed clinically, using various means including cognitive tests and brain imaging, but often when patients are showing symptoms, it is already well past the optimal intervention window. Therefore, early forecasting of AD risk can greatly aid diagnosis and the development of intervention strategies. By combining the new deep learning model with genetic testing, an individual’s lifetime risk of developing AD can be estimated with more than 70% accuracy. AD is a heritable disorder that can be attributed to genomic variants. As these variants are present from birth and remain constant throughout life, examining an individual’s DNA information can help predict their relative risk of developing AD, thereby enabling early intervention and timely management. While FDA-approved genetic testing for the APOE-ε4 genetic variant can estimate AD risk, it may be insufficient to identify high-risk individuals, because multiple genetic risks contribute to the disease. Therefore, it is essential to develop tests that integrate information from multiple AD risk genes to accurately determine an individual’s relative risk of developing AD over their lifetime. “Our study demonstrates the efficacy of deep learning methods for genetic research and risk prediction for Alzheimer’s disease. This breakthrough will greatly accelerate population-scale screening and staging of Alzheimer’s disease risk. Besides risk prediction, this approach supports the grouping of individuals according to their disease risk and provides insights into the mechanisms that contribute to the onset and progression of the disease,” said Prof. Nancy Ip. Meanwhile, Prof. Chen Lei remarked that, “this study exemplifies how the application of AI to the biological sciences can significantly benefit biomedical and disease-related studies. By utilizing a neural network, we effectively captured nonlinearity in high-dimensional genomic data, which improved the accuracy of Alzheimer’s disease risk prediction. In addition, through AI-based data analysis without human supervision, we categorized at-risk individuals into subgroups, which revealed insights into the underlying disease mechanisms. Our research also highlights how AI can elegantly, efficiently, and effectively address interdisciplinary challenges. I firmly believe that AI will play a vital role in various healthcare fields in the near future.” The study was conducted in collaboration with researchers at the Shenzhen Institute of Advanced Technology and University College London as well as clinicians at local Hong Kong hospitals including Prince of Wales Hospital and Queen Elizabeth Hospital. The findings were recently published in Communications Medicine. The research team is now refining the model and aims to ultimately incorporate it into standard screening workflows. AD, which affects over 50 million people worldwide, is a fatal disease that involves cognitive dysfunction and the loss of brain cells. Its symptoms include progressive memory loss as well as impaired movement, reasoning, and judgment.

Hong Kong Center for Neurodegenerative Diseases (HKCeND) participated in the Asia Summit on Global Health (ASGH) on 17 May 2023 at the Hong Kong Convention and Exhibition Centre. The team showcased their latest research breakthroughs and cutting-edge innovations in the field of Alzheimer’s disease. At the event, the team exhibited the first multi-biomarker-based simple blood test for early diagnosis of Alzheimer’s disease, which can detect, diagnose and monitor the disease with an accuracy of more than 96%. This novel solution would revolutionize the large-scale screening and detection of the disease, enabling timely and personalized interventions. In parallel, the team also shared insights on gene therapy, in particular, the promising genome-editing strategy for familial Alzheimer’s disease. This breakthrough provides immense potential to be translated into a new treatment strategy for familial Alzheimer’s disease, offering hope for patients and their families worldwide. Themed “Reimagining the Future of Healthcare”, the ASGH 2023 is a premier platform for health innovation and investment, bringing together all the stakeholders from around the world to exchange insights, explore opportunities and collaborate on the diverse and dynamic healthcare sector. At HKCeND, the team is committed to advancing research in neurodegenerative diseases and delivering healthcare solutions that benefit society.

HKCeND’s neuroscience research has garnered two prestigious awards at the International Exhibition of Inventions Geneva 2023, including the Prize of the Chinese Delegation for Invention and Innovation, as well as the Gold Medal with Congratulations of the Jury. The award-winning innovation is the first multiplex blood biomarker panel designed to assist in early diagnosis of Alzheimer’s disease. With an accuracy of up to 96%, the solution can detect Alzheimer’s 5-10 years before clinical symptoms manifest, and also monitor the progression of the disease. HKCeND Center Director, Prof. Nancy Ip said, ’We are honoured that our innovation has been recognized on a global stage, and we remain committed to advancing our cutting-edge research and translating our achievements into tangible applications that benefit society.’ The International Exhibition of Inventions Geneva is a prestigious international event devoted exclusively to inventions. This year, nearly 1,000 inventions from about 40 countries and regions were showcased, with a total of 293 inventions from Hong Kong participated in the event.

Hong Kong Center for Neurodegenerative Diseases (HKCeND) was featured in the latest episode of the Radio Television Hong Kong (RTHK) programme “I&T New Era II” supported by the Innovation and Technology Commission (ITC). Prof. Nancy Ip, Center Director of HKCeND, was interviewed to highlight that Alzheimer’s disease (AD) had become a growing global health challenge, leading to an urgent need for early diagnosis and effective treatment to fight the disease. In this programme, Prof. Ip also shares three of the translational research breakthroughs of the Center, including the simple but robust blood test for early diagnosis, staging and monitoring of AD, the novel therapeutic approach using brain-wide genome editing technology, and the first scoring system utilizing artificial intelligence (AI) for risk prediction of AD. As one of the R&D centers under InnoHK, a prime initiative by the HKSAR Government to transform the city into a global innovation powerhouse, HKCeND aspires to deliver unparalleled innovation, leading-edge science and technology, and groundbreaking healthcare solutions that bring tangible benefits for patients, caregivers and families affected by neurodegenerative diseases.

Our Assistant Center Director Prof. Tom Cheung was invited by Education Bureau to deliver a lecture titled ’SS Enriching Knowledge Series for Biology: Biotechnology’ in Hong Kong Science Park on 10 Mar 2023. Prof. Cheung introduced some techniques of biotechnology and their applications to the secondary school biology teachers. Followed by the lecture, Prof. Cheung and Dr. Ashley Suen led the teachers for a tour of our research facilities. We are delighted for the opportunity to share our vision and research achievements, particularly in genome-editing technology and early diagnosis of Alzheimer’s disease.

The team of Hong Kong Center for Neurodegenerative Diseases (HKCeND) participated in the Asia Summit on Global Health (ASGH) jointly organized by the Government of the Hong Kong Special Administrative Region and the Hong Kong Trade Development Council on 10-11 November 2022, showcasing major R&D breakthroughs in the healthcare sector. The team, led by Dr. Fanny Ip, Chief Scientific Officer of HKCeND, demonstrated their world-class and impactful research achievements in developing early diagnostic tools and therapeutic strategies for Alzheimer’s disease. Moreover, the ASGH has provided an important platform for the team to exchange insights and explore collaboration opportunities with key industry players and investors. Spearheaded by The Hong Kong University of Science and Technology (HKUST), HKCeND was established in 2020 under the government-funded InnoHK initiative. The team is dedicated to translating cutting-edge research into innovative healthcare solutions that bring hope to millions of patients worldwide.

The HKUST Industry Engagement Day was successfully held today (7 November), with the participation of hundreds of industry players, potential investors, academics, government officials, entrepreneurs, and HKUST researchers. By demonstrating HKUST’s passion and capability in research and development, the event aims to engage industry partners with HKUST researchers to explore collaboration and technology transfer opportunities, thereby driving Hong Kong’s innovation and technology (I&T) development. As one of the research laboratories established by HKUST, Hong Kong Center for Neurodegenerative Diseases (HKCeND) is honored to participate in this event. The HKCeND representatives showcased promising research breakthroughs in the early diagnosis and treatment of Alzheimer’s disease. Apart from the demonstration of research inventions, Dr. Fanny Ip, Chief Scientific Officer of HKCeND, was invited to speak at a thematic session on medical and biotechnology. She shared her insights into molecular diagnostics for Alzheimer’s disease.

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.

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.

The InnoHK Launch Ceremony, organized by the Innovation and Technology Commission of the HKSAR Government, was held on 25 May 2022 at the Hong Kong Science Park. Professor Nancy Ip, Center Director of Hong Kong Center for Neurodegenerative Diseases (HKCeND) and core members were honoured to attend the ceremony. The ceremony marks a new milestone in the government’s commitment to promoting Hong Kong’s innovation and technology (I&T). Being one of the R&D centres under the Health@InnoHK cluster, HKCeND aims to become the world’s leading research center focused on neurodegenerative diseases.

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 enables risk prediction, early detection, and classification of AD. Furthermore, the team has successfully developed a gene therapy strategy as a novel therapeutic treatment for AD. Established in 2020 with an initial funding of HK$500 million from the Hong Kong government’s InnoHK Clusters initiative, HKCeND aims to be the world’s leading research center focused on neurodegenerative diseases. A multi-disciplinary team of prominent scientists from HKUST, University College London and Stanford University School of Medicine are engaged in cutting-edge research 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 there are no objective diagnostic methods and patients are only diagnosed when the disease is at an 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 focusing 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 talent to join the fast-growing team, and is committed to nurturing a new generation of innovation and technology (I&T) talent.