Zooming in on a single disease and studying it intensely is often the most productive route to finding treatments. But there’s no easy way to distinguish among people living with any of the primary tauopathies — a group of rare brain diseases marked by rapidly worsening problems with thinking and movement — because the symptoms are too similar. As a result, most studies on primary tauopathies have included a mix of such diseases, even though researchers know that the diseases differ in important ways and probably require different treatments.
Now, however, researchers have found a biomarker that identifies, with up to 89% accuracy, people with a primary tauopathy called corticobasal degeneration (CBD). Traditional diagnostic methods for CBD are only 25% to 50% accurate, the researchers said.
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.
The study is published in Nature Medicine.
“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 a co-senior author. “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.”
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. 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.
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.
In 2020, the first author on the current paper, developed a highly sensitive technique to detect specific fragments of tau in the cerebrospinal fluid that surrounds the brain and spinal cord. The researchers used the technique to identify a novel form of tau in Alzheimer’s patients, and showed that the level of the novel tau in the cerebrospinal fluid indicates the stage of the disease, and tracks with the amount of tau tangles in the brain.
As part of this study, the researchers used the technique to search for distinctive forms of tau linked to primary tauopathies. To ensure that the study subjects were classified accurately. 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% to 89% 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,” the author 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.”
Several experimental drugs targeting tau are in the pipeline. Most were designed with Alzheimer’s patients in mind, but they may be effective as therapies for primary tauopathies. Horie’s technique could be used to find biomarkers for other primary tauopathies, opening the door to more clinical trials, the researchers said.
“CBD patients and families are desperate for effective therapies, but it has been challenging to organize clinical trials for this fatal disease,” the author said. “Until now, we did not have a specific biomarker to accurately diagnose patients. This new biomarker also opens the door to testing many new tau-directed therapies for CBD, because it may allow us to directly measure the ability of these treatments to lower toxic tau protein levels in patients’ brains.”
https://www.nature.com/articles/s41591-022-02075-9
http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fcsf-tau-microtubule_2&filter=22
Identifying pathological changes in primary tauopathies
- 883 views
- Added
Latest News
Metabolic rewiring promotes…
By newseditor
Posted 18 Apr
A drug to prevent flu-induc…
By newseditor
Posted 18 Apr
New origin of deep brain waves
By newseditor
Posted 17 Apr
Starving cells hijack prote…
By newseditor
Posted 17 Apr
Miniature battery-free epid…
By newseditor
Posted 17 Apr
Other Top Stories
Artificial intelligence for diagnosing dementia
Read more
Protecting the brain from dementia-inducing abnormal protein aggreg…
Read more
Miniature, implantable nerve coolers for targeted pain relief
Read more
Sex differences in the alcohol mediated brain activity
Read more
A novel therapy using unique thermogel prevents retinal scarring
Read more
Protocols
MemPrep, a new technology f…
By newseditor
Posted 08 Apr
A tangible method to assess…
By newseditor
Posted 08 Apr
Stem cell-derived vessels-o…
By newseditor
Posted 06 Apr
Single-cell biclustering fo…
By newseditor
Posted 01 Apr
Modular dual-color BiAD sen…
By newseditor
Posted 31 Mar
Publications
How does the microbiota con…
By newseditor
Posted 18 Apr
The integrated stress respo…
By newseditor
Posted 18 Apr
The immunobiology of herpes…
By newseditor
Posted 17 Apr
Circulating microbiome DNA…
By newseditor
Posted 17 Apr
Spindle oscillations in com…
By newseditor
Posted 17 Apr
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar