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Highly accurate blood tests to diagnose Alzheimer’s disease, the degree of dementia

According to a study by Washington University’s St. Louis Medical School and Lund University in Sweden, a newly developed blood test for Alzheimer’s disease not only helps diagnose the diagnosis of neurodegenerative conditions, but also shows how well it has progressed.

Several blood tests for Alzheimer’s disease are already available clinically, two of which are based on WASHU-licensed technology. These tests help doctors diagnose disease in people with cognitive symptoms, but do not indicate the clinical stage of the disease symptoms, the extent of thinking or memory disorders caused by Alzheimer’s dementia. Current Alzheimer’s treatments are most effective in the early stages of the disease, so adopting a relatively easy and reliable approach to assessing the extent of the disease can help doctors determine which patients may benefit from drug treatment and to what extent. The new test also gives insight into whether a person’s symptoms may be due to Alzheimer’s disease and other causes.

The study was held on March 31 Natural Medicine.

In this study, the researchers found that a protein level in the blood, called MTBR-TAU243, accurately reflects the amount of toxicity accumulation of Tau aggregate in the brain and is related to the severity of Alzheimer’s disease. The researchers analyzed blood levels in a group of people with cognitive decline, and the researchers were able to distinguish between people with early or late stage Alzheimer’s disease and separate the two groups of Alzheimer’s disease from symptoms other than Alzheimer’s disease.

“This blood test clearly identifies tau tangles in Alzheimer’s, which is our best biomarker for Alzheimer’s symptoms and dementia,” Randall J. Bateman, MD, Distinguished Neurology Professor, Charles F. and Joanne Knight, Randall J. Bateman, MD, MD, at Washu Medicine. “In clinical practice, we have no easy or accessible measures for tangle and dementia in Alzheimer’s, so such tangle blood tests can provide better signs if the symptoms are caused by Alzheimer’s symptoms and can also help doctors determine which treatments are best for patients.”

Alzheimer’s disease involves the accumulation of a protein called amyloid into brain plaques, which then develops in tau tangles many years later. During detectable tau tangles, cognitive symptoms appear, which worsen as the tangles spread. The gold standard for staging in Alzheimer’s disease is positron emission tomography (PET) brain scans amyloid plaques and tau tangles. Amyloid scans produce information about the pre-symptom and early symptom phases, while TAU scans are useful for tracking later stages of the disease. Pet brain scans are very accurate, but are expensive, time-consuming and often unavailable outside major research centers and therefore will not be widely used.

Bateman leads a team that is developing blood tests for Alzheimer’s disease as an easier-to-access alternative to brain scans. They developed two blood tests that are closely related to the amount of amyloid plaques in the brain. Both are now used by doctors to aid diagnosis. But until now, no blood tests on tau levels in the brain have been performed.

In previous research, Bateman and colleagues—including first author Kanta Horie, PhD, associate professor of neurologic research at Washu Medicine, and Postdoctoral researcher Gemma Salvadó, Lund University, and co-author Oskar Hansson, MD, MD, Phd, Phd, Phd plas of lund coreply of Lunder corefors of core cores of core coremallloginal of Lund coref. MTBR-TAU243 is closely related to Tau tangles in the brain. In the current study, the team extends the analysis to the blood. Blood samples are easier to collect than cerebrospinal fluid, which is obtained through a spinal faucet.

The researchers developed a technique to measure the MTBR-TAU243 levels in people’s blood and compared it with the amount of Tau tangle in the brain measured by brain scans. They tried the method of data from two similar data: Charles F. and Joanne Knight Alzheimer’s Disease Research Center at Washu Medicine, which included 108 people, and 55 people from Swedish BioFinder-2 classmates. To evaluate whether the method can be generalized, they validated the method in an independent dataset consisting of the remaining 739 people in their BioFinder-2 counterparts.

In addition to elevating at the symptom stage, people in both cohorts remain healthy by early disease with mild cognitive impairment until patients exhibit late blood. For comparison, cognitively healthy patients with normal amyloid levels included, and those with cognitive symptoms caused by diseases other than Alzheimer’s disease.

The researchers’ analysis showed that blood MTBR-TAU243 levels reflect the amount of Tau tangle in the brain with a 92% accuracy. Regardless of the state of amyloid, the blood levels of MTBR-TAU243 in asymptomatic people are normal, meaning that blood levels of MTBR MTBR-TAU243 between healthy people and healthy people and healthy people will not change.

Among patients with cognitive symptoms caused by Alzheimer’s disease, MTBR-TAU243 levels were significantly elevated in people at the mild cognitive impairment stage of Alzheimer’s disease, and the number was as high as 200 times during the dementia stage. These differences translate into a clear separation in people with early and late Alzheimer’s disease. Meanwhile, MTBR-TAU243 levels are normal due to people with cognitive symptoms caused by diseases other than Alzheimer’s, meaning the test effectively distinguishes Alzheimer’s from other types of dementia.

The basic technology for TAU aggregate blood test has been licensed by WASHU to C2N Diagnostics, a WASHU startup that developed amyloid blood tests. These amyloid tests combine another measure of TAU called P-TAU217.

“I believe we will use blood-based P-TAU217 to determine if a person has Alzheimer’s disease, but MTBR-TAU243 will be a very valuable addition in both clinical settings and in research trials,” Hansen said. “When both biomarkers are positive, Alzheimer’s disease is a significant increase in the root cause of cognitive symptoms in a person compared to p-TAU217 alone. This distinction is critical to selecting the most appropriate treatment for each patient.”

Blood tests can inform personalized Alzheimer’s treatment

The Food and Drug Administration (FDA) has approved two Alzheimer’s treatments to slow the disease progression, and both work by reducing amyloid levels in the brain. The number and variety of Alzheimer’s drugs may soon expand, Horry said, as several experimental drugs targeting tau or other aspects of Alzheimer’s disease are in the pipeline. Through blood tests for diagnosing and staging the disease, doctors will be able to tailor treatment to the patient’s specific disease state.

“We are about to enter the age of personalized medicine in Alzheimer’s disease,” Horry said. For the early stages of low tau tangle, anti-amyloid therapy may be more effective than late. However, anti-Tau entanglement, anti-TAU therapy, anti-TAU therapy, or one of many other experimental methods may be more effective after a dementia attack using high tau tangles. Once we have clinically treated the clinical treatments, as well as clinical treatments at various stages, as well as clinical treatments at different stages, and treatments at different stages, these stages can be performed at different stages of the doctor’s specific stages.

Horie K, Salvadó G, Koppisetti RK, Janelidze S, Barthélemy NR, He Y, Sato C, Gordon BA, Jiang H, Benzinger TLS, Erik Stomrud E, Holtzman DM, Mattsson-Carlgren N, Morris JC, Palmqvist S, Ossenkoppele R, Schindler SE, Hansson O, Bateman RJ. Plasma MTBR-TAU243 identified tau tangle pathology in Alzheimer’s disease. Natural medicine. March 31, 2025. DOI: 10.1038/S41591-025-03617-7.

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