Plasma EMTBR-TAU243 shows a strong correlation with tau pathology and cognitive decline, and offers a less invasive alternative to TAU-Pet imaging.
Study: Plasma MTBR-TAU243 Biomarker identifies Tau Tangle Pathology in Alzheimer’s disease. Image Credit: Gorodenkoff/Shutterstock.com
Tau protein clonts that form neurofibrillary tangles (NFTs) are a decisive characteristic of Alzheimer’s disease (AD), the main cause of dementia worldwide. There is a growing demand for an affordable, accessible and less invasive test that can detect Tau -Pathology to help with the diagnosis, to guide the treatment decisions and follow the progression of disease.
A recent study published in Nature Medicine Introduces a blood test that focuses on a specific insoluble form of Tau – that promotes a potential breakthrough in how we approach Alzheimer’s diagnostics.
Introduction
Alzheimer’s disease leads to progressive, irreversible cognitive decline and affects millions of older adults worldwide. Two abnormal proteins are consistently found in the brains of people with AD: amyloid-β (Aβ) plaques and tau-based NFTs.
Anti-amyloid immunotherapies have demonstrated promising and delayed the cognitive and functional decline of 25%-40%. However, they are most effective if Tau -Pathology is limited -relieving the need for early, accurate detection of Tau building in the brain.
Identifying a peripheral biomarker that reliably follows Tau pathology could fill this gap. Unlike AP -accumulation – that can be present in people without symptoms – TAU changes changes more closely with disease progression.
This type of marker would not only improve diagnostic accuracy, but also support the development of targeted anti-TAU treatments, possibly used in addition to anti-amyloid therapies for a more extensive approach.
Tau-Pet Imaging versus Flowing Biomarkers
Tau-Pet scans are currently the gold standard for assessing tau pathology in symptomatic patients. However, they are expensive and are not available on a large scale. Liquid biomarkers, on the other hand, offer a more cost-effective and scalable solution-nous restricted for routine clinical institutions and point-of-care tests.
Existing liquid biomarkers include Aβ42/40 ratios and fosphorylated TAU shapes such as P-TAU181 and P-TAU217, measured in both cerebrospinal liquid (CSF) and plasma.
Although useful, these markers are more strongly connected to Aβ plaque -presence than for the formation of Tau -Wirwar.
In earlier work, researchers used mass spectrometry to detect CSF levels from P-TAU205 and MTBR-TAU243 (a fragment from Tau’s Microtubule-binding region with residue 243). Although informative, this approach is still based on lumbar puncture, which is invasive and entails certain risks.
In this new study, the team introduces a blood-based biomarker-endogen split MTBR-TAU243 (EMTBR-TAU243)-which avoids restrictions. The researchers have carried out two pilot studies and a larger validation study, in which EMTBR-TAU243 levels were compared with cognitive assessments, Aβ-Pet, Tau-Pet and MRI data.
They also compared the performance with existing plasma biomarkers, in particular %P-TAU181 and %P-TAU217.
Important findings
The study showed that Plasma EMTBR-TAU243 correlates with both plasma and CSF-TAU-PET image formation, in contrast to MTBR-TAU243, which only aligns with CSF data.
In the pilot studies, EMTBR-TAU243 levels were significantly higher to 200-time-in patients with established AD compared to people with mild cognitive disorders (MCI) or an early stage disease. In particular, this marker has not risen in people who had AP plaques, but no cognitive symptoms.
In the larger clinical study, EMTBR-TAU243 remained stable in cognitive normal individuals, regardless of AP status. However, levels have mainly increased in people with MCI, which suggests that the biomarker can help patients stratify per disease phase. It also remained specifically for AD, without increasing non-ad tauopathies.
For comparison: Plasma %P-TAU217 was followed with Ad-Ererst, but was also increased in AP-positive individuals without symptoms. A similar but more variable pattern was observed for %P-TAU205.
All three markers-emtbr-TAU243, %P-TAU217 and %P-TAU205-Werden associated with TAU-PET position. However, EMTBR-TAU243 showed the strongest and most linear relationship, even as the severity of the disease increased.
While %P-TAU217 levels tended to be Plateau, EMTBR-TAU243 continued to rise, which reflected a closer link to the current Tangargang accumulation.
Among AP-positive individuals, 59% tested negatively for both Tau-Pet and EMTBR-TAU243, while 30% were positive for both. Discordant results were less common at EMTBR-TAU243 (7%) compared to%P-TAU217 (41%), which further supports the further coordination between EMTBR-TAU243 and TAU-Pet findings.
Regional, EMTBR-TAU243 levels that are strongly correlated with TAU-PET position in brain areas that are usually influenced later in the disease, which is particularly useful to follow more advanced stages of AD.
Multivariate analysis confirmed that EMTBR-TAU243 catches this later phase of TAU pathology in a unique way, while %P-TAU217 is more closely matched to earlier, ap-driven changes.
EMTBR-TAU243 also had the strongest associations with brain atrophy, early cognitive decline and global cognitive scores in individuals who are positive for AP or Tau-Pet.
Implications
If validated in larger populations, this blood test can significantly improve the way in which we diagnose Alzheimer’s and control.
By identifying Tau Pathology earlier and more accurately, clinics can coordinate treatments based on the disease phase and possibly improve the results.
Researcher Kanta Horie explained the potential shift that this entails:
“We are about to enter the age of personalized medicine for Alzheimer’s disease. For early stages with low Tau tables, anti-amyloid therapies can be more effective. But as soon as dementia is committed and Tau-Klit accumulates, therapies against Tau or other experimental approaches can be better.”
Conclusion
This study introduces Plasma EMTBR-TAU243 as a promising biomarker for detecting and monitoring advanced Tau pathology in Alzheimer’s disease.
It performs better than existing markers in predicting the findings of Tau-Pet and correlates stronger with cognitive decline and brain atrophy.
As a potential alternative to TAU-Pet, EMTBR-TAU243 could offer a practical, non-invasive tool for clinical examinations and daily practice, improve diagnostic precision and help supervising treatment decisions based on the disease radium.
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