<p>Blood-based biomarkers (BBBs) are rapidly reshaping how Alzheimer’s disease (AD) is diagnosed and managed. New US Food and Drug Administration (FDA)–cleared plasma assays now allow clinicians to confirm or exclude AD biology with a relatively high sensitivity and specificity, potentially unlocking a broader access to a variety of treatment options, including disease-modifying therapies (DMTs).</p>

Once DMTs became available, biomarker verification using positron emission tomography (PET) scanning and cerebrospinal fluid (CSF) analysis also became part of the clinical workup that was required to prescribe these DMTs. However, biomarker PET scans and CSF analysis had inherent challenges. For PET scans, the patient needed to be close to a major medical center that was well resourced, and CSF analysis has always been limited by the fact that it is such an intrusive intervention. To improve the utility of biomarkers, we needed to be looking at something that had better scalability, that was easier to obtain, and with a lower cost. That is how BBBs came to be.

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We often say that things in AD have moved slowly, except for the development of BBBs. There has been significant progress in the sensitivity and specificity of BBBs for AD over the past 5 years, although particularly over the last 2 years. This has led to the FDA clearances of 2 BBB tests.

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One test, which was FDA cleared in May 2025 for use as part of a clinical evaluation for a memory disease, can rule in AD, thus actually meeting the criteria for biomarker verification for treatment with humanized monoclonal antibodies targeting amyloid-β. This test, the Lumipulse G pTau217/β-Amyloid 1-42 Plasma Ratio (Fujirebio), had equivalent sensitivity and specificity to the already approved Lumipulse CSF test (ie, the Lumipulse G β-Amyloid Ratio [Fujirebio]). The Lumipulse BBB test has a cutoff for a positive result and a cutoff for a negative result. Between these 2 cutoffs is an indeterminate measure, where the test cannot speak to whether the results are positive or negative.

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The second BBB test for AD was cleared by the FDA in October 2025. This BBB test is on the Elecsys platform, which is another analyzer that is highly sensitive, and is called the Elecsys pTau181 plasma test (Roche). It measures pTau181, which is associated with AD pathology, and was cleared for use in primary care to exclude AD by ruling out the presence of amyloid plaques in patients older than 55 years presenting with signs or symptoms of cognitive impairment. If you score below the cutoff, AD is likely not the cause of your symptoms. A positive result indicates that further testing is needed for a definitive diagnosis.

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Although the details are still being worked out, when talking with my colleagues, they have told me that they are using these BBB tests first line. And then, if you get indeterminate results, most of us move to an amyloid PET scan. None of the blood tests can reliably tell us yet when to stop treatment. The exact utility of these tests outside of diagnostics is still not fully established, but there are studies ongoing to help us fully understand the potential that these BBBs may bring. In the future, similar to a cholesterol profile, we may have something like an AD profile, where each test may have a different role and utility depending on what you are looking for, whether it is diagnostics, treatment selection, or monitoring. BBBs have also opened the window for the potential future broad screening of people who may be at risk for developing AD so that we can offer preventive interventions to reduce cognitive decline.