EDGE 10 11 HKUST Alumni In a landmark breakthrough, the first multi-protein blood test for the early detection of Alzheimer’s disease (AD) and mild cognitive impairment (MCI) has been developed by the HKUST and the Hong Kong Center for Neurodegenerative Diseases (HKCeND). Spearheaded by HKUST President Professor Nancy Ip, the pioneering research team includes Professor Amy Fu, Research Professor at HKUST’s Division of Life Science, and Dr. Fanny Ip, Chief Scientific Officer at HKCeND - both HKUST PhD Biology graduates. “This is the first multi-protein blood test for AD and MCI. We developed it based on the results of our large-scale and comprehensive screening of AD blood biomarkers. This blood test has the potential to revolutionize AD diagnosis and management. It’s simple, highly accurate, non-invasive, and cost-effective, and can be applied to diverse ethnic populations,”says Prof. Fu. A disease affecting lives globally AD affects over 55 million people worldwide, imposing immense burdens on the economy and society. Early detection and timely intervention are important for mitigating the impacts of AD. The new blood test provides a reliable solution for the early detection and monitoring of AD and MCI. This can help medical professionals to identify individuals at risk of AD or showing early signs of pathological changes, so they can administer timely disease management strategies. The blood test could also facilitate population-wide screening, according to Dr. Ip: “Overall, the early detection and close monitoring of MCI and AD will empower individuals to better understand their brain health and take proactive measures, such as lifestyle modifications and personalized disease management strategies, leading to improved health outcomes and quality of life. Ultimately, the test will lead to the development of precision medicine and can improve healthcare resource allocation as well as reduce societal and economic burdens.” A decade-long battle The team started patient recruitment and sample collection for this project 10 years ago. In 2019, they were able to start developing new AD blood biomarkers and assays because of advances in protein detection technologies. Clinical diagnosis of AD mainly relies on cognitive assessment, which is subjective, and brain imaging or cerebrospinal fluid assessment, which are expensive and/or invasive. The new blood test is a game-changer, providing a remarkably accurate, convenient, and non-invasive tool for early detection and monitoring of the disease. “Our blood test simultaneously measures the levels of 21 proteins associated with multiple biological processes involved in AD development. By capturing a more comprehensive profile of the AD blood, our test reveals the development of pathological changes in the brain and accurately detects AD with over 96% accuracy and MCI with over 87% accuracy,”says Prof. Fu. The majority of existing AD blood biomarker studies focus on developing bloodbased assays for the pathological hallmarks of AD such as amyloid-beta and tau proteins. Nonetheless, capturing a more comprehensive profile of the dysregulation of biological processes, such as inflammation and the vascular functions, by a blood-based test, may help better evaluate the progression of the disease, particularly at the early stage. Chip and algorithms make their mark Using cutting edge technology, the team developed an integrated blood assay chip that simultaneously measures 21 key AD blood biomarkers with high precision, based on their large-scale proteomic profiling study in 2021. They further developed a machine learning-based algorithm to calculate AD risk score for individuals, based on the levels of these 21 blood proteins. The team optimized this scoring system by training it on more than 2,000 human plasma samples from diverse ethnic groups, which enables the blood test to accurately evaluate an individual’s AD status. Driving towards global impact The team is currently preparing a clinical research program in multiple regions and countries – the first stage includes Hong Kong, Mainland China, the US, and some countries in Europe – to gather more clinical data to validate and optimize the blood testing technology, and ultimately benefit the global population with the blood test for AD. “Our test can be used in clinical settings to help the screening of individuals with early AD or MCI, as well as the monitoring of disease progression and drug responses. This will greatly facilitate targeted clinical trials, says Dr. Ip. “It can also help reveal potential disease-causing factors in the blood in AD, which can serve as novel targets for the development of drugs and therapeutic strategies,”she adds. About the team Professor Amy Fu, Research Professor, Division of Life Science, HKUST “I was originally a technician in Prof. Nancy Ip’s lab at HKUST,” recalls Prof. Fu.“I then transitioned into a PhD program, focusing on basic neuroscience, with the same team.”Prof. Fu played a critical role in developing the platform and databases for AD in the Chinese population.“Everything began from scratch,”she explains.“We established the research paradigm, pipelines, and protocols. We published the first paper on understanding of the regulation of synapse communication in Nature Neuroscience. I’m proud that we developed all the most advanced approaches and technologies in a lab here for diagnostic and drug target studies for AD at HKUST, and in Hong Kong.” Dr. Fanny Ip, Chief Scientific Officer, Hong Kong Center for Neurodegenerative Diseases (HKCeND) “I was the first PhD student in Prof. Nancy Ip’s lab at HKUST in 1993,”says Dr. Ip.“Determined to unlock the secrets of the human brain and find a cure, I’ve been researching brain degeneration ever since.”In recent years, Dr. Ip has shifted to developing novel diagnostics and treatments for neurodegenerative and neurological disorders.“Now, I’m working closely with our teams and diverse stakeholders to translate our research discoveries into tangible solutions,” she adds. For Dr. Ip, this achievement is a proud moment not just for her, but for the entire team and HKUST community. “This is a true testament to HKUST’s research excellence and innovation,”she says. Breakthrough in the fight against Alzheimer’s An HKUST team has developed the first comprehensive blood test for early Alzheimer’s disease.
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