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ST. LOUIS — For decades, definitively diagnosing Alzheimer’s disease required looking directly at the brain—either through costly imaging or by sampling spinal fluid. Now, researchers have discovered a telltale marker in blood that reveals the presence of brain tau tangles, a hallmark of Alzheimer’s. This breakthrough blood test could transform care for millions worldwide by making diagnosis simpler, more affordable, and widely accessible.

The newly discovered biomarker, called eMTBR-tau243, reflects the presence of tau protein clumps—the neurofibrillary tangles that characterize Alzheimer’s disease and closely track symptom progression. Until now, confirming these changes required expensive brain scans or uncomfortable spinal taps to collect fluid from around the brain and spinal cord.

Researchers from Washington University and Lund University examined blood samples from over 900 participants across different stages of Alzheimer’s. They found that levels of eMTBR-tau243 were significantly higher in people with mild cognitive impairment due to Alzheimer’s and even higher in those with dementia. Their results are published in Nature Medicine.

What sets this biomarker apart is its precision. Unlike other blood tests that measure different forms of tau protein, eMTBR-tau243 shows remarkable correlation with actual tau tangles in the brain. It also distinguishes Alzheimer’s from other brain disorders that can cause similar symptoms, such as frontotemporal dementia or progressive supranuclear palsy.

“This blood test clearly identifies Alzheimer’s tau tangles, which is our best biomarker measure of Alzheimer’s symptoms and dementia,” says co-senior author Dr. Randall J. Bateman, a professor of neurology at WashU Medicine, in a statement. “In clinical practice right now, we don’t have easy or accessible measures of Alzheimer’s tangles and dementia, and so a tangle blood test like this can provide a much better indication if the symptoms are due to Alzheimer’s and may also help doctors decide which treatments are best for their patients.”

Transforming Treatment Approaches

Recent trials have shown that treatments targeting amyloid—another protein that accumulates in Alzheimer’s—can slow cognitive decline by 25-40% in symptomatic individuals. However, these therapies appear to work better in patients with lower levels of tau tangles.

A reliable blood test for tau tangles could help doctors determine which patients might benefit most from these treatments. It could also speed up drug development by providing a simpler way to monitor whether experimental therapies are affecting the underlying disease process.

Through careful laboratory work, study authors identified a unique tau fragment with specific modifications that seems to be released from brain tau aggregates. The fragment appears in blood at levels that closely track brain changes visible on specialized PET scans.

The researchers’ analysis showed that blood MTBR-tau243 levels reflected the amount of tau tangles in the brain with 92% accuracy. Remarkably, the test effectively distinguished between early- and late-stage Alzheimer’s disease. Among people with cognitive symptoms, MTBR-tau243 levels were significantly elevated for those in the mild cognitive impairment phase and much higher—up to 200 times—for those in the dementia phase.

From Lab Discovery to Clinical Impact

The potential applications of this blood test extend far beyond diagnosis. It could enable routine screening for Alzheimer’s risk in older adults, possibly detecting the disease process years before symptoms become noticeable. For those already experiencing memory problems, it could help determine whether Alzheimer’s is the cause and how likely they are to progress to dementia.

For clinical trials testing new treatments, the biomarker could serve as a biological indicator of whether interventions are working. This could accelerate the development of more effective therapies, particularly those targeting tau tangles directly.

“I believe we will use blood-based p-tau217 to determine whether an individual has Alzheimer’s disease, but MTBR-tau243 will be a highly valuable complement in both clinical settings and research trials,” notes co-senior author Dr. Oskar Hansson, a professor of neurology at Lund University. “When both of these biomarkers are positive, the likelihood that Alzheimer’s is the underlying cause of a person’s cognitive symptoms increases significantly, compared to when only p-tau217 is abnormal. This distinction is crucial for selecting the most appropriate treatment for each patient.”

The technology underlying this blood test has been licensed by Washington University to C2N Diagnostics, a WashU startup that previously developed blood tests for amyloid. According to lead author Kanta Horie, PhD, a research associate professor at WashU Medicine, the future of Alzheimer’s care is headed toward personalized approaches.

“We’re about to enter the era of personalized medicine for Alzheimer’s disease,” Horie says. “For early stages with low tau tangles, anti-amyloid therapies could be more efficacious than in late stages. But after the onset of dementia with high tau tangles, anti-tau therapy or one of the many other experimental approaches may be more effective. Once we have a clinically available blood test for staging, plus treatments that work at different stages of the disease, doctors will be able to optimize their treatment plans for the specific needs of each patient.”