Blood-based biomarkers for Alzheimer’s are simpler, cheaper and less invasive than methods used currently. Their greater accessibility could improve the timeliness of diagnosis and care.
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Blood biomarkers are obtained from a simple blood sample, making them less invasive than other methods for detecting AD pathology.Credit: stefanamer/iStock/Getty
“It’s alarming how bad the situation is,” says Ambar Kulshreshtha a family medicine physician at Emory University in Atlanta, Georgia. He is referring to the ever-growing rate of Alzheimer’s disease (AD), which is placing a huge burden on health systems worldwide. An ageing global population means the number of people with dementia is now 55 million, yet 75% of those people are undiagnosed.
Diagnosis is getting quicker and easier, however. The latest development is to detect proteins linked to neurodegeneration, which leak from the brain to the blood. Quantities are tiny, which hampered efforts to find them for many years. But technical advancements in understanding and measuring these blood-based biomarkers (BBMs) have made these tests comparably sensitive to existing diagnostic methods.
Multiple studies have reported accuracies above 90% for detecting AD pathology using the p-Tau 217 isoform, or algorithms including a combination of biomarkers. Performance criteria for BBMs have been agreed, and validated tests meeting these standards, such as those developed by Lucent Diagnostics (part of Quanterix), C2N Diagnostics and AlzPath, are considered suitable for confirmatory diagnostic use1,2. As a consequence, thought leaders, including the Alzheimer’s Association, have revised criteria for the diagnosis and staging of AD to include BBMs.
The next step is implementing these tests into clinical care. The current diagnostic gold standards are analysis of proteins in cerebrospinal fluid (CSF) and PET scans of brain amyloid (and, more recently, tau). These tests can identify AD pathology with high accuracy, but they are expensive and invasive. They tend to be available only in specialist centres, which limits the ability of people to access them. Nearly a fifth of Americans live in rural areas, which often don’t have easy access to these specialist centres, including a disproportionate number of some ethnic minorities who are at higher risk for AD. Veterans, and less wealthy people, are also over-represented in rural areas. This creates a health disparity, contributing to underdiagnosis.
One key question is how best to deploy these BBM tests to increase early diagnosis, reduce underdiagnosis, and ensure that more people can access diagnostic testing. Might the answer be to move these tests from specialist memory clinics to an expanse of other clinical settings?
Expanding reach
AD, as a specific form of dementia, has traditionally been a difficult diagnosis to confirm. “When it comes to interpreting an extensive cognitive battery, brain imaging, blood-based or spinal fluid biomarkers, someone trained in that area of practice needs to continue doing that,” says Antoine Raynard Trammell, a memory disorder specialist at Emory University. “It takes a lot to put that picture together.” Given this challenge, a definitive diagnosis will likely remain in the specialist setting.
Where BBMs can effect the greatest change is in improving the ability of primary care providers, and other non-specialist clinics, to triage patients — using the tests to preferentially refer people to specialists without delay, while also limiting referrals of those who are unlikely to benefit.
Because they don’t suffer from the capacity constraints of amyloid PET and CSF methods, BBM tests can be more easily scaled up to be used in non-specialist settings and find many more people who would potentially benefit from the new wave of disease-modifying therapies (DMTs) that have recently come to market2.
And there is a big need for these tests. Kulshreshtha recently shared preliminary results at the 2024 American Geriatrics Society conference, showing that in patients aged 65 or older, recruited from primary care clinics for low-income populations, 62% had mild cognitive impairment, while 12% had undiagnosed dementia.
AD patients in the United States can wait around 50 months3 for access to DMTs — potentially up to three times longer if they live in rural areas. Care models allowing primary care practitioners to diagnose using BBM tests, and assess treatment eligibility could significantly reduce specialist wait times and increase the number of patients treated. “Do I think more primary care clinics should be using blood biomarker tests? Heck yes!” says Trammell. “If they can combine the results with an abnormal cognitive test, we may catch cases earlier.”
Putting biomarkers into practice
As BBM tests become more commonplace, clinicians need to be clear around how demographic and health factors affect them. “With BBMs, you have to think about heart health and kidney health, because these things are filtering the blood,” says Trammell. Clinical studies are underway that will help provide the necessary evidence.
In the meantime, a multitude of AD experts are working to see how BBMs can be successfully implemented into more clinical settings. In June 2024, the Davos Alzheimer’s Collaborative launched a new initiative to deploy BBMs and confirmatory diagnostic testing in health systems across five countries, to increase timely and accurate diagnosis of AD and related dementias. “This pioneering study will not only help us better understand the predictive value of these biomarkers in real world populations, but also prepare us for their implementation into clinical care,” says Fanny Elahi, a neurologist at Icahn School of Medicine at Mount Sinai, New York. The sites, including Mount Sinai, were selected based on their scientific expertise in BBM research and clinical capabilities, and their ability to reach patients across ages, racial and ethnic backgrounds, education levels, socioeconomic status and geographic settings.
“Given the diverse population Mount Sinai serves, we’ll be able to test the effects of medical co-morbidities, sex/gender and race/ethnicity on the association of plasma biomarkers with clinical outcomes,” says Elahi. Four partners, including Lucent Diagnostics, are providing in-kind contributions of BBM and/or CSF test kits to support the project. The goal is to enable healthcare providers to use these tests in everyday clinical practice — accelerating the translation of validated tools from research to timely patient care.
“This is a revolutionary moment in dementia treatment and diagnosis, because of the availability of good biomarkers,” says Kulshreshtha. “Realizing a diagnosis can lead to treatment will encourage people to seek testing, and primary care physicians will gain confidence as data shows how these tests guide patient care.” If doctors at all levels of clinical care can be armed with accessible, easily administered tests, it will not only improve early detection, but also go a long way towards making Alzheimer’s diagnosis equitable. Trammell concludes: “Making these tests widely available and affordable is key to maintaining societal health.”
Click here to learn more about Lucent Diagnostics’ product and service offerings, including LucentAD p-Tau 217 assay, or email [email protected]
References
Alzheimer’s Association Workgroup: Revised Criteria for Diagnosis and Staging of Alzheimer’s Disease. Available at: https://aaic.alz.org/diagnostic-criteria.asp
Schinder SE, Galasko D, Pereira AC, et al. Nat Rev Neurol. (Published online June 12, 2024).
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Mattke S & Hanson M. Alzheimer’s Dement, 18:1071–1074 (2021).
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