English
Alzheimer’s disease has long been a challenge for the medical community. Traditional diagnostic methods, while effective, come with their own set of limitations. However, the landscape of Alzheimer’s disease screening is transforming thanks to advances in blood-based biomarkers that offer the promise of a less invasive and more accessible alternative to cerebrospinal fluid (CSF) biomarkers or positron emission tomography (PET) imaging. The following is a Q&A with Dr. Arindam Ghosh, Alzheimer’s disease and dementia specialist.
Q: Why blood-based biomarkers for Alzheimer’s disease?
A: With the continuing rise in global life expectancy comes a host of health-related side effects. One of these is dementia, with the number of individuals living with Alzheimer’s disease expected to triple by 2050.1 While there are new treatments available and others on the horizon, they can’t be prescribed without a concrete diagnosis.
Alzheimer’s disease wasn’t defined until the early 20th century, and the only way to truly know that someone had Alzheimer’s disease was through autopsy of the brain, and the line between cognitive decline with normal aging and pathologic decline associated with Alzheimer’s disease has remained blurry. In the late 20th/early 21st century, CSF analysis and PET testing became available to measure the buildup of amyloid proteins in the brain, but these tests are expensive and not scalable. We’re making progress, but with the forecasted increase in the incidence of Alzheimer’s disease over the next few decades, we need other testing options.
Recently, a group of world-renowned neurologists and neuroscientists wrote a consensus statement—the CEOi study—which discussed how incorporating blood-based biomarkers into testing could become routine for people presenting for cognitive impairment evaluation.2 They believed that integration of blood-based biomarkers into the regular screening processes could improve early detection of Alzheimer’s disease. This approach promised not only to be less invasive but also more accessible and affordable, allowing for earlier detection and intervention.
Q: How do blood-based biomarkers for Alzheimer’s disease work?
A: There are several biomarkers—measurable indicators of a normal or abnormal process, disease, or condition—that change in neurodegenerative diseases. To replace CSF and PET scans effectively, blood-based biomarker combinations and panels need to demonstrate concordance with amyloid PET and CSF tests. In Alzheimer’s disease, levels of biomarkers change at different times along the disease continuum. Of the known biomarkers, levels of ß-amyloid in the CSF are altered first, often before symptoms arise. Next, phosphorylated tau levels rise. The tau protein can be phosphorylated on either amino acid 217 or 181. pTau-217 levels rise before pTau-218 levels do.3 While the biomarker levels are highest in the central nervous system, they can cross the blood brain barrier and enter the bloodstream, where they can be more readily measured.
Once biomarkers are identified, the risk or presence of Alzheimer’s disease in patients can be assessed. The CEOi study discussed the advantages and limitations of blood-based biomarkers noting the need for further validation in larger, diverse cohorts to ensure their reliability and generalizability across different populations, but they don’t recommend a single biomarker test as a standalone diagnostic test for symptomatic Alzheimer’s disease.2
Q: Why is advancing blood-based biomarkers important?
A: Many of the available disease modifying therapies (DMTs) for Alzheimer’s disease are more effective in the early stages of disease. For example, aducanumab and lecanemab target the prodromal and early dementia stages.4 Further, the FDA has stated that it is best to treat Alzheimer’s disease patients as early as possible,5 necessitating diagnostics that identify disease sooner.
Advancing blood-based biomarkers can help in the early detection of Alzheimer’s disease and significantly impact the course of the disease, allowing for timely interventions that can slow progression and improve quality of life. Making these screenings accessible in primary care settings democratizes the diagnostic process, ensuring that more patients can benefit from early and accurate detection, which can lead to better, more effective treatment.
Currently, blood tests are only recommended for those patients with memory complaints and not for pre-clinical testing. And all positive and intermediate blood-based test results require reflex testing with CSF and PET. But as blood-based biomarkers become more accessible and accurate, fewer people will need confirmatory reflex testing and patients will receive disease modifying therapies faster.
Q: Will blood-based biomarker screening replace PET/CSF?
A: As I mentioned, traditional Alzheimer’s disease diagnosis relies heavily on imaging. While reliable, these tests are also expensive, invasive, and not readily available or accessible in all healthcare settings. Blood-based biomarkers offer a compelling alternative. We have a global shortage of neurologists and dementia specialists—and wait times to see them are long. With an accurate, sensitive blood-based biomarker screening test, primary care physicians could conduct initial screenings, streamlining the diagnostic process and reserving more invasive procedures when needed for confirmation rather than initial detection.
Policy makers and healthcare systems need concrete guidelines for regulating informed and meaningful access to blood biomarkers, particularly with the advent of novel treatment strategies. The CEOi has specific requirements for blood-based tests—they must have sensitivity of at least 90% and specificity of “≥85% in primary care and ≥75–85% in secondary care depending on the availability of follow-up testing,”2—providing the same level of sensitivity as PET scanning.
Blood-based biomarkers represent a promising future for Alzheimer’s disease screening. Overcoming challenges and standardizing tests is vital to enable neuroinflammatory biomarkers to enhance and democratize the diagnosis and prognosis of Alzheimer’s disease. With ongoing research and development, particularly from industry leaders like Beckman Coulter, we are on the cusp of a new era in the fight against Alzheimer’s disease. These advancements will not only enhance early detection but also pave the way for more effective treatments and improved patient outcomes.
Q: How is Beckman Coulter supporting blood-based biomarkers for Alzheimer’s disease?
A: At Beckman Coulter, we are at the forefront of advancing blood-based biomarkers for Alzheimer’s disease and other neurodegenerative diseases. Our efforts are focused on developing and refining assays that can detect these biomarkers accurately and with high sensitivity. Through extensive research and collaboration with leading institutions, we aim to bring these diagnostic tools to clinical practice. We are committed to ensuring that these tests are not only reliable, sensitive, and specific, but also accessible to a broad range of healthcare providers and their patients.
Learn more about our commitment to developing blood-based biomarkers for early Alzheimer’s disease research.
