Plasma biomarker measuring tau tangles aids diagnosis and offers clinicians insight into disease stage and likely trajectory.
A newly developed blood test may soon transform the clinical assessment of Alzheimer’s disease, offering not only a means to detect the condition but also a way to measure how far it has progressed. The test identifies a specific tau protein fragment in the blood – plasma MTBR-tau243 – that reflects the accumulation of insoluble tau tangles in the brain, a hallmark of Alzheimer’s pathology and a key driver of cognitive decline.
Published in Nature Medicine, the research led by scientists at Washington University School of Medicine in St Louis and Lund University in Sweden evaluated the performance of this plasma biomarker in over 900 individuals across the Alzheimer’s disease continuum [1]. Their findings suggest that MTBR-tau243 may complement existing biomarkers to improve diagnostic precision – particularly in identifying whether Alzheimer’s is the cause of a person’s cognitive symptoms – and help guide treatment choices based on disease stage.
Longevity.Technology: The introduction of plasma eMTBR-tau243 represents more than a technical advance in biomarker science – it signals a pragmatic shift toward more equitable, earlier and stage-sensitive care in Alzheimer’s disease. By enabling accurate staging of tau pathology through a simple blood test, the approach not only facilitates timely intervention but also enhances the feasibility of delivering precision medicine across varied healthcare contexts. In doing so, it holds relevance beyond individual clinical encounters – potentially reshaping how neurodegenerative diseases are managed at a population level, particularly in settings where specialist imaging infrastructure is scarce. As longevity increases globally, tools that promote healthspan – preserving function and autonomy for longer – are increasingly central to both personal and public health strategies; in that regard, the validation of eMTBR-tau243 may prove to be as socially significant as it is scientifically.
Tau tangles – dense, twisted strands of tau protein – are a defining hallmark of Alzheimer’s disease. Their presence correlates more strongly with dementia symptoms than the amyloid plaques that also characterize the condition [2]. Until now, assessing tau pathology has required positron emission tomography (PET) imaging, an expensive and resource-intensive technique available only at specialized centers.
The blood test addresses this limitation by detecting a cleaved and chemically modified form of tau, called eMTBR-tau243, which mirrors the presence of tangles identified by PET imaging. Elevated levels were observed only in symptomatic stages of Alzheimer’s and not in cognitively unimpaired individuals who had amyloid plaques – a crucial distinction, since many older people have amyloid without experiencing dementia [1].
“This blood test clearly identifies Alzheimer’s tau tangles, which is our best biomarker measure of Alzheimer’s symptoms and dementia,” said co-senior author Randall J Bateman, MD, the Charles F and Joanne Knight Distinguished Professor of Neurology at WashU Medicine. “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 [3].”
The test’s utility lies not just in its specificity for tau pathology, but in its ability to reflect disease stage. MTBR-tau243 levels in blood rose significantly at the mild cognitive impairment phase and increased further in dementia, aligning closely with both cognitive scores and brain atrophy as measured by MRI. Compared with other plasma biomarkers such as p-tau217 and p-tau205, MTBR-tau243 showed stronger and more linear correlations with tau-PET imaging – especially in later stages of tau accumulation.
In contrast, p-tau217 was found to be more sensitive in early pre-symptomatic phases, often elevated in amyloid-positive individuals without dementia. As a result, researchers suggest the two biomarkers may be used in tandem.
“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,” said Professor Oskar Hansson of 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 [3].”
The development of MTBR-tau243 also represents a methodological advancement. The researchers used a mass spectrometry approach targeting a specific region of tau (the microtubule-binding repeat region) that is highly enriched in Alzheimer’s tangles. The cleaved form of the protein, ending at residue 256 with a deamidated residue 255, was detectable in blood and closely mirrored changes seen in cerebrospinal fluid and PET imaging. The specificity of the biomarker for tauopathy of the Alzheimer’s type was further supported by its absence in non-Alzheimer’s neurodegenerative conditions, such as frontotemporal dementia and progressive supranuclear palsy.
The broader implications of this test may lie in its ability to stratify patients for clinical trials and optimize therapeutic decisions. Anti-amyloid therapies, such as lecanemab, are most effective at early stages when tau burden is low; conversely, tau-targeting treatments may be better suited once tau pathology has advanced.
“We’re about to enter the era of personalized medicine for Alzheimer’s disease,” said Kanta Horie, PhD, one of the study’s lead authors. “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 [3].”
Clinical validation will be required before MTBR-tau243 testing becomes routine; current measurement requires relatively large volumes of plasma and specialist mass spectrometry equipment, though future iterations of the assay may simplify the process for wider implementation.
As the field moves towards more nuanced definitions of Alzheimer’s disease based on biological changes rather than symptoms alone, tests such as these represent a step toward precision diagnostics. While no single biomarker offers a complete picture, MTBR-tau243 may soon provide a critical missing piece – linking pathology to clinical presentation in a way that can guide care and therapeutic decisions.
The development of this blood test marks a shift in approach – from detecting disease presence to understanding disease stage; in doing so, it offers clinicians the tools to move closer to personalized treatment for patients with Alzheimer’s disease.
[1] https://www.nature.com/articles/s41591-025-03617-7[2] https://jamanetwork.com/journals/jamaneurology/fullarticle/2735107
[3] https://medicine.washu.edu/news/highly-accurate-blood-test-diagnoses-alzheimers-disease-measures-extent-of-dementia/
Main photograph: FabrikaPhoto/Envato. In-article photograph: Matt Miller.
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