New Blood Test Could Personalize Alzheimer’s Treatment Like Never Before

A new Alzheimer’s blood test could bring doctors closer to personalized treatment by revealing how far the disease has progressed.

Over the past few years, blood tests have transformed how Alzheimer’s disease is diagnosed. Since C2N Diagnostics’ PrecivityAD™ became available in 2020, it has offered a more accessible and less invasive option for detecting early Alzheimer’s disease. Its successor, PrecivityAD2™, launched in 2023, further improved diagnostic accuracy by measuring two key proteins linked to Alzheimer’s: amyloid-beta and tau. The company received early support from BrightFocus Foundation‘s Alzheimer’s Disease Research program to develop these blood tests.

Now, researchers at Washington University in St. Louis have developed a new kind of blood test—one that selectively measures a novel form of tau closely tied to Alzheimer’s tau tangles. In an international collaboration, BrightFocus Alzheimer’s Disease Research grant recipient Gemma Salvadó, PhD, validated the blood test using samples from the Swedish BioFINDER-2 (Biomarkers For Identifying Neurodegenerative Disorders Early and Reliably) study at Lund University.

This next-generation blood test promises to do more than diagnose: it may help determine how far the disease has progressed and identify who is most likely to benefit from today’s anti-amyloid therapies.

Inside the BioFINDER Study

Three years ago, Dr. Salvadó joined the laboratory of Oscar Hansson, MD, PhD, at Lund University after completing her PhD at the Barcelonaßeta Brain Research Center in Spain. She describes Dr. Hansson as a world leader in Alzheimer’s disease biomarkers, prompting her to join his research team.

Dr. Hansson has led the BioFINDER study at Lund University since its inception in 2007. Ten years later, he began the Swedish BioFINDER-2 extension study to enhance early diagnosis, monitoring, and understanding of Alzheimer’s disease and other neurodegenerative disorders. The BioFINDER research group has been “testing and validating plasma biomarkers since their appearance,” said Dr. Salvadó.

They closely collaborate with a research group at Washington University St. Louis led by Randall Bateman, MD, the scientific co-founder of C2N Diagnostics. In fact, Dr. Hansson and Dr. Salvadó helped validate the PrecivityAD2™ blood test using the BioFINDER study cohort.

That blood test measures a specific tau marker, called phosphorylated-tau217 (p-tau217), known for its ability to accurately reflect brain amyloid pathology early in the disease. However, amyloid pathology is not as specific to Alzheimer’s as one might think, cautions Dr. Salvadó. When there is one neurodegenerative disease, it is often not the only disease in the brain, and amyloid pathology can co-occur with other diseases.

“You may have a positive test because you have some amyloid in your brain, but the symptoms that you have are not due to this amyloid because you have something else that is causing these symptoms,” she explained. Prior research shows that tau tangles are more strongly linked to cognitive decline in Alzheimer’s than amyloid plaques.

Researchers needed a tau marker with stronger ties to tangles—and a test that doesn’t require an expensive brain scan or painful spinal tap. Studies examining tangles found in human brain samples uncovered a biomarker called microtubule-binding region containing residue 243 (MTBR-tau243). This specific form of tau is closely linked to the tangles that build up in the brains of people with Alzheimer’s, making it a strong candidate for tracking disease progression.

Dr. Salvadó first sought to examine MTBR-tau243 in living people by examining their cerebrospinal fluid. She confirmed that this biomarker can accurately characterize tau pathology in the brain. Backed by funding from Alzheimer’s Disease Research, she moved a step further by taking her investigation of MTBR-tau243 into the blood.

Staging Alzheimer’s—Without Expensive, Invasive Tests

Dr. Bateman’s research team designed a new test to measure MTBR-tau243 in blood samples and used the BioFINDER-2 cohort to validate the test’s ability to accurately diagnose Alzheimer’s and determine disease severity.

Study findings confirmed that blood MTBR-tau243 levels are more specific to Alzheimer’s disease tau tangles than the previous marker, p-tau217. The new marker also showed a stronger association with loss of brain volume and cognitive symptoms observed in participants with Alzheimer’s. The researchers concluded that this enhanced specificity means the new blood test has strong potential use for diagnosing and staging the disease.

“Some people may have tau, but due to other progressive brain diseases,” explained Dr. Salvadó. “This marker was specific to participants with Alzheimer’s, so it may help us have a more accurate diagnosis in the future.”

Over half of older adults with dementia have a mixed form, meaning they have more than one neurodegenerative disease. In these cases, amyloid-beta and phosphorylated-tau biomarkers may be positive, but not the primary cause of cognitive impairment. Measuring MTBR-tau243 bypasses this complication, allowing physicians to get a clearer picture of the causes for cognitive decline and design treatment plans accordingly.

Current blood tests can diagnose the disease but cannot pinpoint how far it has progressed. Determining how much Alzheimer’s has advanced means undergoing multiple specialized, expensive brain scans.

When compared head-to-head, p-tau217 showed a stronger connection to earlier disease stages, while MTBR-tau243 tied into later stages. One blood test alone can detect disease, but it’s not enough, and certainly not ideal, said Dr. Salvadó.

“When you go to an oncologist, they don’t just diagnose whether or not you have cancer,” she explained. “Is it a small or big tumor? Has it metastasized? Is it in a small part of your body? These are the kind of things we are trying to do by using multiple biomarkers.”

A Future of Personalized Treatment

Dr. Salvadó pictures a future where physicians use multiple blood tests to better determine Alzheimer’s severity and create tailored treatment plans. “With two [blood tests], maybe we can say that you are in the earlier stages, like only having one tumor in one part of your body,” she said, “or it’s in the later stages, and we have to use different therapies and be more aggressive because the disease is more advanced.”

Recent clinical trials have shown that those with lower levels of tau pathology are responding better to anti-amyloid treatments like Leqembi and Kisunla. The MTBR-tau243 blood test, with its close association to brain tau tangles, could also help physicians determine who is most likely to benefit from these kinds of treatments in the future.

“The possibility of staging individuals and categorizing participants by their characteristics at that moment may allow us to treat everyone with better drugs for them,” she said.

What’s Next

Dr. Salvadó is now back in Spain as a group leader at Barcelonaßeta Brain Research Center, splitting her time between there and Lund University with Dr. Hansson’s research group.

Her work continues to focus on advancing staging techniques for Alzheimer’s and examining how to best apply biomarkers in the clinic. She remains interested in how these tools can help doctors deliver the right Alzheimer’s treatment, at the right time. Though more research is needed, Dr. Salvadó ultimately hopes these tools will one day be part of routine clinical practice and bring precision medicine closer to reality in Alzheimer’s care.

Looking back, Dr. Salvadó feels gratitude for the many people who helped make this research possible. “Thank you to the BrightFocus donors for your support. And to all the people who gave their time, samples, and effort to allow us to do this kind of research.”

BrightFocus Foundation’s Alzheimer’s Disease Research program is committed to advancing next-generation diagnostic tools, including blood tests and biomarker research that can lead to earlier, more accurate, and more personalized care. Explore our funded research in this area.