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Diagnostic biomarker to detect rare brain condition found

Individual tauopathies involve different subtypes of tau and exhibit different patterns of damage to brain cells and tissues.

Diagnostic biomarker to detect rare brain condition found
Representative image

WASHINGTON DC: Researchers have found a biomarker that identifies a rare brain disease called corticobasal degeneration (CBD) with higher accuracy than traditional diagnostic methods, according to a study. The biomarker that identifies a primary tauopathy increases CBD detection accuracy to 89 per cent compared to traditional methods that are only 25 per cent to 50 per cent accurate, scientists at the Washington University said.

Primary tauopathies are a group of rare brain diseases marked by rapidly worsening problems with thinking and movement, the study published in Nature Medicine said. CBD is a rare condition that can cause gradually worsening problems with movement, speech, memory and swallowing, and is one of the tauopathies.

The biomarker could be developed into a tool to screen potential volunteers for CBD-specific research studies and clinical trials and, eventually, to identify people who could benefit from CBD-specific treatments, the scientists said.

''Before, the only way to find out which primary tauopathy a person had was to wait until they died and then examine the person's brain under a microscope,'' said co-senior author Chihiro Sato.

''A patient comes in with stiffness, balance problems, slurred speech and memory issues, and it could be CBD, but it also could be progressive supranuclear palsy (PSP) or Alzheimer's or other diseases.

''This biomarker can reliably identify people with CBD, which means we can use it to enroll people in clinical trials. And, down the road, it may be key to initiating therapies,'' said Sato.

CBD is one of about two dozen brain diseases that are considered tauopathies because they share one critical feature: toxic tau aggregates in the brain. Tau tangles are abnormal accumulations of a protein called tau that collect inside neurons.

In healthy neurons, tau normally binds to and stabilizes microtubules. However, in conditions such as in Alzheimer's disease, abnormal chemical changes cause tau to detach from microtubules and stick to other tau molecules, forming threads that eventually join to form tau tangles inside neurons.

Individual tauopathies involve different subtypes of tau and exhibit different patterns of damage to brain cells and tissues.

The collections of symptoms of the various tauopathies overlap, making it difficult for doctors to tell one from another. This complicates efforts to study them and find treatments, the study said.

Tauopathies are classed as either primary or secondary, depending on when tau tangles appear in the course of the disease.

In primary tauopathies, tau tangles form in the beginning, seemingly on their own. In secondary tauopathies, tangles form only after other changes have taken place in the brain.

For example, in Alzheimer's disease, the most common secondary tauopathy, the brain protein amyloid beta builds up for years before tau tangles appear.

As part of this study, the researchers used a highly sensitive technique to detect specific fragments of tau in the cerebrospinal fluid that surrounds the brain and spinal cord to search for distinctive forms of tau linked to primary tauopathies.

The team examined brain tissues and cerebrospinal fluid from people who had died with dementia and movement disorders, and whose specific diseases had been confirmed at autopsy.

The study population included people with one of five primary tauopathies — CBD, PSP, frontotemporal lobar degeneration with microtubule association protein tau mutations (FTLD-MAPT), agyrophilic grain disease, and Pick's disease — as well as Alzheimer's, and dementia not related to tau.

For comparison, they also examined samples from people without dementia.

Two particular forms of tau — microtubule binding region (MTBR)-tau 275 and MTBR-tau 282 — were unusually high in the brains and low in the cerebrospinal fluid of patients with CBD and a subset of FTLD-MAPT.

Further investigation showed that these forms of tau distinguish people with CBD from those with other primary tauopathies with 84 per cent to 89 per cent accuracy, depending on the disease.

''Even if there's an experimental drug available that specifically targets the kind of tau in CBD, it is very challenging to test it without a biomarker,'' study author Kanta Horie said.

''The trial might fail even when the drug works if the population is heterogenous. Drug trials that specifically target the kind of tau in CBD can be improved by enrolling correctly diagnosed patients.

''Having a biomarker opens up a pathway for pharmaceutical companies to improve clinical trials and accelerate research toward therapies for CBD,'' said Horie.

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