Blood Test Identifies Alzheimer's Before Symptoms Appear with 92% Accuracy

A new blood test could help diagnose Alzheimer’s disease. The test measures a protein called eMTBR-tau243, which is directly linked to the buildup of tau in the brain, a key sign of the disease. The results showed that this biomarker can indicate the severity of the disease and predict its progression more accurately than previous tests. This could facilitate early diagnosis and improve monitoring of new treatments.

Alzheimer’s disease is characterized by the buildup of two proteins in the brain: beta-amyloid (Aβ) and tau. Treatments that target beta-amyloid have been shown to reduce cognitive decline in some people with the disease.

However, these treatments appear to be most effective in people who have low levels of the aggregated tau protein in their brains. This is because about 25% of older adults have beta-amyloid plaques but no symptoms of the disease, meaning that a test that detects beta-amyloid alone is not enough to confirm the cause of the cognitive problem.

Thus, identifying and measuring the accumulation of tau protein may be essential to determine who can truly benefit from therapies.

Tau protein is essential for the functioning of neurons, helping to stabilize their structure. However, in diseases such as Alzheimer’s, tau can accumulate and form tangles in the brain, impairing communication between neurons and leading to cell death.

This process is directly linked to the decline in memory and other cognitive functions, making increased tau one of the main signs of disease progression and a major challenge for treatment.

Tau accumulation has been a target of increasing interest because it is more directly linked to the progression of Alzheimer’s disease than beta-amyloid. Combining anti-tau therapies with current anti-beta-amyloid therapies could offer a more effective treatment. However, for this to be possible, reliable tests that detect pathological changes in tau in the brain are needed.

In Alzheimer’s disease, the tau protein, which normally helps keep neurons healthy, can become defective and form tangles in the brain. These tangles spread in a specific pattern, as if traveling along a network of connections between neurons. Scientists believe that this spread of tau may be a key reason why the disease worsens over time, affecting more and more areas of the brain responsible for memory and other cognitive functions. Source: Shuko Takeda. Volume 13 - 2019

One of the most accurate ways to assess tau protein in the brain is through positron emission tomography (PET). This test uses a radioactive tracer that binds to tau tangles in the brain and allows the image of their accumulation.

Studies have shown that elevated levels of tau detected by PET are strongly linked to cognitive decline. Despite its accuracy, this test is expensive and requires sophisticated equipment, which limits its accessibility. In comparison, biomarkers found in blood or cerebrospinal fluid (CSF) are cheaper and easier to obtain, making them a promising alternative for identifying the disease.

Current fluid-based tests measure fragments of the phosphorylated tau protein (p-tau), such as p-tau181 and p-tau217. However, these forms of tau are more closely related to the presence of beta-amyloid than to the actual accumulation of insoluble tau in the brain.

This means that they can indicate early changes in the disease, but they do not directly measure the tau tangles that cause neuronal degeneration. Recent clinical trials have shown that anti-beta-amyloid therapies reduce levels of these proteins in blood and CSF, but do not directly affect tau tangles, reinforcing the need for more specific biomarkers for aggregated tau. 

Amyloid PET Scan for Alzheimer's Disease Assessment

To address this problem, researchers at Washington University School of Medicine in the US have developed a new mass spectrometry-based test called eMTBR-tau243. This test measures a specific form of the tau protein in the blood that better reflects the presence of aggregated tau in the brain.

In studies involving three different groups of patients (totaling 739 people), levels of this biomarker in the blood were elevated in the early stages of the disease and increased further as dementia progressed.

Furthermore, the results showed that eMTBR-tau243 in blood correlated strongly with tau PET findings, indicating that it could be a reliable substitute for this more expensive test.

In addition to identifying the presence of the disease, the new biomarker has also proven useful in predicting cognitive decline and assessing the efficacy of new treatments.

This could make clinical trials more efficient, helping to better select participants and monitor the impact of anti-tau therapies. Because it is based on a blood sample, this test has the potential to be widely used, making Alzheimer’s disease diagnosis more accessible and accurate for patients worldwide.

READ MORE:

Plasma MTBR-tau243 biomarker identifies tau tangle pathology in Alzheimer’s disease

Kanta Horie, Gemma Salvadó, Rama K. Koppisetti, Shorena Janelidze, Nicolas R. Barthélemy, Yingxin He, Chihiro Sato, Brian A. Gordon, Hong Jiang, Tammie L. S. Benzinger, Erik Stomrud, David M. Holtzman, Niklas Mattsson-Carlgren, John C. Morris, Sebastian Palmqvist, Rik Ossenkoppele, Suzanne E. Schindler, Oskar Hansson and Randall J. Bateman

Nature Medicine. 31 March 2025

DOI: 10.1038/s41591-025-03617-7

Abstract: 

Insoluble tau aggregates within neurofibrillary tangles are a defining neuropathological feature of Alzheimer’s disease (AD) and closely correlate with clinical symptoms. Although tau pathology can be assessed using tau positron emission tomography, a more accessible biomarker is needed for diagnosis, prognosis and tracking treatment effects. Here we present a new plasma tau species, the endogenously cleaved, microtubule-binding region containing residue 243 (eMTBR-tau243), which specifically reflects tau tangle pathology. Across the AD spectrum in three different cohorts (n = 108, 55 and 739), plasma eMTBR-tau243 levels were significantly elevated at the mild cognitive impairment stage and increased further in dementia. Plasma eMTBR-tau243 showed strong associations with tau positron emission tomography binding (β = 0.72, R2 = 0.56) and cognitive performance (β = 0.60, R2 = 0.40), outperforming other plasma tau (%p-tau217 and %p-tau205) biomarkers. These results suggest that plasma eMTBR-tau243 may be useful for estimating the tauopathy load in AD, thereby improving the diagnostic evaluation of AD in clinical practice and monitoring the efficacy of tau-targeted therapies in clinical trials.