“This blood test clearly identifies Alzheimer’s tau tangles, which is our best biomarker measure of Alzheimer’s symptoms and dementia,” said Dr. Randall J. Bateman, a world-leading professor of neurology at Washington University School of Medicine. These words capture a breakthrough shift in Alzheimer’s diagnosis a blood test not only identifying the disease’s presence but also its trajectory with high precision.
Alzheimer’s disease, a neurodegenerative condition that is marked by cognitive impairment, has long relied on costly and invasive testing in order to make a diagnosis. Positron emission tomography (PET) scans, the current gold standard for amyloid plaque and tau tangle detection, are regularly unavailable outside of large research centers. This has left a critical gap in being able to adequately stage the disease, particularly within primary care practice. The new blood test, which is derived from the protein MTBR-tau243, aims to close this gap and offer a less painful and more accessible alternative.
In a Nature Medicine study, researchers demonstrated that blood levels of MTBR-tau243 closely correlate with tau tangles in the brain with 92% accuracy. The protein levels were normal in healthy subjects with normal cognition, even in those who had elevated amyloid plaques, but skyrocketed in mild cognitive impairment patients and late dementia. This discrimination will allow clinicians to differentiate early versus late Alzheimer’s disease and even discriminate Alzheimer’s-related dementia from other neurodegenerative illness.
The importance of this discovery cannot be overstated. Treatments for Alzheimer’s, such as the FDA-approved drugs donanemab and lecanemab, are most effective when the tau pathology is still low in the early phases of the disease. With a measurable indication of the progression of the disease, the blood test could potentially allow treatment to be personalized to the patient. “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,” said Dr. Kanta Horie, research associate professor at Washington University.
This technology has been licensed to C2N Diagnostics, a company that had previously developed blood tests for amyloid plaques. Whereas those previous tests, e.g., p-tau217 tests, have proven helpful in Alzheimer’s identification, they fall short of this level of accuracy when it comes to staging the disease. MTBR-tau243 emerges as a critical adjunct, particularly in clinical trials and high-end diagnostics. As per 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.”
The creation of MTBR-tau243 as a blood-based biomarker is based on previous research using cerebrospinal fluid. Earlier studies had shown that MTBR-tau243 levels in the spinal fluid were consistent with tau tangles in the brain. Extending the analysis to the blood samples required new techniques, including mass spectrometry, to accurately quantitate the amounts of the protein. It was validated by results in two pilot cohorts the Charles F. and the Joanne Knight Alzheimer Disease Research Center in St. Louis and the Swedish BioFINDER-2 cohort along with an independent larger sample of 739 participants.
The volunteers spanned the spectrum of Alzheimer’s severity from presymptomatic with amyloid plaques to those with severe dementia. Within these groups, MTBR-tau243 levels showed linear correlation with disease severity and rose up to 200-fold in later stages. Unlike other markers such as p-tau217 that plateau with rising tau pathology, MTBR-tau243 shows continued rises and is therefore more in keeping with accumulation of tau tangles.
This linear correlation also holds in downstream effects of Alzheimer’s pathology, e.g., cognitive impairment and brain atrophy. In multivariate analysis, MTBR-tau243 was superior to other plasma biomarkers for prediction of these outcomes, making it of value for purposes of disease tracking. Specificity of the biomarker to Alzheimer’s was also evident in its consistency in non-Alzheimer’s tauopathies such as progressive supranuclear palsy and frontotemporal dementia.
The potential for this blood test to revolutionize Alzheimer’s treatment is immense. By enabling personalized treatment plans, it could optimize therapeutic outcomes and reduce the effects of invasive diagnostic procedures.
The era of tailor-made medicine for Alzheimer’s is on the horizon. With tools like MTBR-tau243, physicians will someday have the capability to match therapy to every patient’s individual requirements, revolutionizing the face of neurodegenerative medicine.
For doctors, neurologists, and researchers, this innovation brings a glimpse of a future in which Alzheimer’s diagnosis is not just more convenient but also more precise, paving the way for individualized treatment and improved patient outcomes.
