With the administration change in Washington, questions abound regarding the impact of new healthcare appointees across healthcare agencies. While it will take time to enact any presumed or planned policy change, one thing is fairly certain: we’re likely to see an increased emphasis on preventive healthcare. Many devastating diseases such as Alzheimer’s can be delayed or potentially prevented if treated earlier, underscoring the ongoing need for more effective proactive tools in diagnosing and managing these diseases.
In these cases, in this current moment, our best hope to reduce both the tragic patient impact and immense health system burden is early detection and proactive disease management. We hope, of course, this tactic changes with pending prevention trials planned in disorders like Alzheimer’s disease (AD). As two individuals who have spent our careers dedicated to clinically impactful diagnostic development, we’ve seen firsthand how blood-based biomarkers are revolutionizing the detection and management of neurodegenerative diseases, particularly AD, by offering non-invasive, cost-effective, and timely diagnostic solutions. As the number of people living with dementia is estimated to grow to more than 152 million by 2050, substantially impacting low-and middle-income countries, there is an urgent need to address the societal burden of AD and prioritize early detection.
The clinical and economic need for blood-based biomarkers
While the advancement of Alzheimer’s treatments over the last two years should be applauded, many patients face a long and difficult diagnostic journey before receiving an accurate diagnosis. The diagnosis timeline for a patient with AD can take around 2.8 years, and about 75% of people with symptoms don’t even realize they have AD. As the pool of approved therapies continues to (hopefully) expand, the clinical and diagnostic testing communities need to do a better job at ensuring the right patients move through this journey more quickly – and accurately – to improve their health and prognosis. Importantly, those that are experiencing cognitive issues, that are not caused by Alzheimer’s, are highlighted quicker and receive a differing management plan without this long diagnostic journey.
Historically, patients have relied on invasive, costly, and logistically complex tools like PET (positron emission tomography) scans and CSF (cerebrospinal fluid) testing to receive a diagnosis. But these are the fortunate ones. Limited access and long delays hinder timely assessment by these innovative tools and thus, a delay in intervention during critical treatment windows for anti-amyloid therapies. Earlier diagnosis of AD is critical, as some treatments are more effective in the early stages. Certain criteria now acknowledge a “preclinical” state of disease, where symptoms are not apparent, and AD pathology is present. Blood-based biomarkers present an opportunity for a cost-effective, accessible and scalable solution that can detect neurogenerative diseases sooner to improve patient outcomes.
The promise of blood-based biomarkers
Blood-based biomarkers, particularly p-tau217, deliver highly accurate diagnostics, rivaling traditional methods. The non-invasive nature of this blood-based biomarker reduces patient burden and expands its accessibility globally. And while there’s been plenty of attention on the validity of one test vs. another, just a few weeks ago, an opinion piece in STAT noted that clinicians “aren’t sure what to do with a positive result.” New research is changing that.
According to findings in a study from Nature Aging, on which Dr. Ashton was a co-author, p-tau217 is highly accurate at ruling in or ruling out AD pathology based on specific clinical and demographic contexts. Depending on the patient’s age, clinical syndrome, and APOE ε4 carrier status, p-tau217 demonstrated as high as >95% positive predictive value (PPV) in ruling in AD and as high as >90% negative predictive value (NPV) for ruling it out. Further, we were able to deduce that cutting-edge assays like GFAP and NfL complement p-tau217, highlighting the broader potential for multiplex diagnostic panels.
What does this mean for those clinicians who aren’t sure what to do with a positive test? Change is coming.
Practical implications for clinicians
Clinicians have traditionally relied on outdated methods to diagnose AD by observing cognitive decline ( e.g., changes in their thinking, learning and/or memory), at which point the disease has already likely caused irreversible brain damage. Blood-based biomarkers provide actionable insights for clinicians facing patients with cognitive impairments, helping them streamline decisions. This enables clinicians to confidently determine a diagnosis without requiring multiple confirmation tests, saving precious time on the patient treatment journey.
The data further supports that in some contexts, p-tau217 can reduce reliance on costly PET scans and CSF testing, streamlining the diagnostic journey for AD and reducing burden on the health care system. These scans and tests are often only available at specialized clinics, can take hours to complete and receiving results can take more than a week. Removing this step from the diagnostic timeline narrows the gap between diagnosis and initiation of anti-amyloid therapies, which is crucial given the narrow therapeutic window.
PET scans and CSF tests can also incur expensive out-of-pocket costs for patients – with PET scans typically costing around $3,000 without insurance and patients paying about 20% of the costs after meeting their deductible. Removing the need for them altogether helps eliminate access barriers and reduces costs for patients.
Beyond streamlining the diagnostic journey for AD patients, blood-based biomarkers also hold near-term potential to be used as eligibility tools for clinical trials. By assessing patient risk for developing AD and potentially monitoring progression of the disease, these tests can facilitate screening and identification of patients who require further evaluation or who may benefit from a specific trial, as well as aiding in the development of new AD therapeutics.
Clinical implementation gap
Despite technological advances, there remains a need to transition from innovative tests to real world applications. Adoption and standardization of blood-based biomarkers in clinical settings can only be fully realized when clinicians, industry stakeholders and policymakers come together. And beyond p-tau217, we must collectively recognize how much more clinical impact could be possible through a deeper understanding of blood-based biomarkers.
Blood-based biomarkers not only have the transformative potential to advance neurodegenerative disease research and treatment by streamlining the diagnostic process and therapeutic drug trials, but they may one day improve health outcomes and decrease expenses for financially vulnerable patients. Although preventative interventions for AD don’t exist yet, we should take action by embracing blood-based biomarker innovations to enhance healthcare accessibility and drive the next wave of advancements in Alzheimer’s care.
Image credit: Google Science Fair
Dr. Nicholas Ashton is a world leader in the development, validation and use of fluid biomarkers, including cerebrospinal fluid and blood tests, in the fight against Alzheimer’s disease and related disorders. He is the senior director of the Banner Research Fluid Biomarker Program. Dr. Ashton is advancing biomarker research, working closely with academic and industry researchers inside Arizona and around the world. The program is establishing a destination center for the development and use of cerebrospinal fluid and blood-based biomarkers in the fight against Alzheimer’s disease and related disorders.
Dr. Ashton received his Ph.D. in 2017 from King’s College London in the group of Professor Simon Lovestone and has been an associate professor in the group of Henrik Zetterberg and Kaj Blennow at University of Gothenburg, Sweden since 2019. Dr. Ashton has a decade of experience in biofluid analysis and assay development for Alzheimer’s disease and related disorders.
Masoud Toloue is the CEO of Quanterix. With a career spanning leadership positions in both private and publicly traded companies, he has consistently commercialized disruptive technologies and scaled businesses to achieve exceptional results.Prior to joining Quanterix, Masoud served as Senior VP of Diagnostics at PerkinElmer, where he successfully grew the business unit to contribute over 50% of the company’s total revenue. Earlier at PerkinElmer, he led the Applied Genomics business. His entrepreneurial acumen is evidenced by his role as founder and leader of Bioo Scientific’s next-generation sequencing business, which was acquired by PerkinElmer in 2016. He also co-founded and led Genohub, transforming it from a supplier of sequencing-matching technology into a global platform for managing sequencing projects.
Masoud holds a doctoral degree in molecular cell biology from the University at Buffalo and completed a postdoctoral fellowship in protein biochemistry at The University of Texas Health Science Center in San Antonio.
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