New Delhi: Researchers may have found a way to simplify the process of identifying and tracking the progression of Alzheimer’s — the debilitating neurodegenerative disease that is believed to be the most common cause of dementia — by identifying a form of key protein that could serve as a marker to track the progression of the disease.
Alzheimer’s is marked by the formation of abnormal protein structures, called plaques — made of beta-amyloid proteins — outside the brain’s neurons, which disrupts the normal functioning of the brain, and the irregular buildup of tau protein, called tau tangles, inside the neurons.
Measuring tau tangles in the brain is challenging, but now, this complex process may have become simpler.
Researchers from Sweden, Netherlands and the US have identified a fragment of the tau protein called, MTBR-tau243, in the fluid surrounding the brain and spinal cord.
With this finding, doctors and scientists may be able to track the progression of Alzheimer’s by simply following the MTBR-tau243 fragment, instead of the entire protein, which can make the process easier and less dependent on complex imaging.
Currently, the most common biomarkers used to diagnose the disease are amyloid protein, tau protein, and phospho-tau.
According to researchers, the finding of the tau protein fragment can help make MTBR-tau243 become a specific and precise biomarker assessment tool, for an accurate diagnosis of the progression of Alzheimer’s, after enough clinical trials have been done to check its efficacy.
The findings were published in the Nature Medicine journal on 13 July.
The tau protein is essential to stabilise the internal skeleton of nerve cells (neurons) in the brain. But Alzheimer’s disease is marked by an abnormal tau build-up. Collection and deposition of the tau protein cause toxicity, which in turn leads to neuronal degeneration.
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Measuring tau tangles
Currently, the most reliable way to measure tau tangles in the brain is by using a technique called positron emission tomography (PET) imaging. However, this technique is expensive and requires a complicated infrastructure, so it can only be done in highly specialised centres.
“The tau-PET is the most accurate prognostic marker of Alzheimer’s disease available today,” the researchers wrote.
With fluid biomarkers, like MTBR-tau243, which are less costly to identify and more clinically accessible, things may change soon, the researchers added. These fluid biomarkers refer to measures that can be obtained from the body’s cerebrospinal fluid and plasma.
Cerebrospinal fluid (CSF) is a clear, plasma-like fluid that traverses regions of the brain and the spinal canal and binds the central nervous system. It protects the brain by acting as a shock absorber as it cushions the brain against the skull. It is continuously secreted to provide stability to the brain.
So far, there are some fluid biomarkers that can measure tau tangles, but they mostly measure the increase of amyloid plaques rather than finding the insoluble tau clumps, which are more important for Alzheimer’s, according to the authors.
Amyloid plaques are another form of protein clumps, which grow in the gaps between nerve cells. These improperly structured proteins are also considered to be a crucial marker of Alzheimer’s disease.
Therefore, the researchers decided to investigate MTBR-tau243, which had been previously “poorly investigated” as a potential marker for Alzheimer’s.
In an earlier study with 35 Alzheimer’s patients, the researchers found the MTBR-tau species and confirmed that it was present in the cerebrospinal fluid. Moreover, in the same study, they also found that MTBR-tau species with a molecule called residue 243 (MTBR-tau243) was strongly linked with disease progression.
To further confirm these findings, the researchers decided to evaluate MTBR-tau243 as a potential biomarker, by comparing its presence with available amyloid and tau PET images from two cohorts of people with Alzheimer’s disease (448 people and 219 people, respectively).
They also compared other biomarkers in the cerebrospinal fluid to measure tau, such as p-tau181, p-tau205, p-tau217 and p-tau231 and found that MTBR-tau243 was the “most strongly associated” with the levels of tau observed in PET images.
“MTBR-tau243 was also the biomarker that was most related to clinical cognitive changes in people with Alzheimer’s disease. It best reflects disease progression in late stages,” the authors added.
(Edited by Richa Mishra)
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