Alzheimer's disease: Tau proteins aggregate to neurofibrillary tangles and neuritic plaques in a neuron axon
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Researchers at Washington University School of Medicine in St. Louis and Lund University in Lund, Sweden, have identified a form of the infamous Alzheimer’s biomarker tau that could be used to track progression of the disease.

There are two main pathologies driving the progression of Alzheimer’s disease. During the onset of the condition, amyloid beta plaques are the key players in neuronal degeneration. However, as the disease develops and cognitive decline becomes apparent, tau tangles take the lead in causing neuronal damage.

Measuring Alzheimer’s disease progression could provide important information for diagnosis and treatment of the condition. However, so far tracking tau particles in the brain has proven a challenge. Reporting in Nature Medicine, researchers have now identified a form of tau—known as microtubule binding region (MTBR)-tau243—that can track the amount of damaging tau tangles in the brain as well as the degree of cognitive decline in patients.

“This discovery provides biomarkers to specifically track the progression of tau tangles, the major pathology that predicts dementia and cognition, which is something that hasn’t been within reach until now,” said Randall Bateman, MD, professor of neurology at Washington University and co-senior author of the study.

“These findings will help accelerate drug development for patients with symptoms of Alzheimer’s disease. We are also working on developing these biomarkers as a clinical test to stage individual patients and improve patient care.”

In a previous study, published in the journal Brain the researchers discovered that levels of MTBR-tau243 in the cerebrospinal fluid (CSF) reflected the number of tangles in the brain in 100 individuals. For their new study, the scientists analyzed CSF samples from over 600 volunteers in Sweden and the U.S, including healthy people as well as individuals at various stages of Alzheimer’s disease.

The scientists compared cognitive function of the patients with levels of various forms of tau in the CSF and with levels of amyloid and tau in the brain, measured by PET scans— the gold standard for quantifying tau tangles in the brain. According to the researchers, levels of MTBR-tau243 in the CSF strongly correlated with brain tau tangle levels and cognitive function. In contrast, levels of a different form of tau known as phosphorylated tau were not able to track cognitive decline.

“To accurately diagnose Alzheimer’s disease in patients with cognitive symptoms, we need biomarker-based evidence of both amyloid beta plaques and tau tangle pathology,” said Oskar Hansson, PhD, professor of neurology at Lund University and co-senior author of the study.

“With this new biomarker, representing tau pathology, we can do this using a single cerebrospinal fluid sample. This has the potential to clearly improve the diagnostic as well as prognostic work-up of Alzheimer’4uys worldwide. We hope that we soon can do the same using a simple blood test.”

The researchers believe that a CSF test based on MTBR-tau243 could speed up drug development for Alzheimer’s disease by providing an easy and inexpensive way to monitor participants in clinical trials compared to expensive PET-scans. By taking repeated CSF samples, the scientists could also assess whether experimental therapies, including tau-targeting drugs, can alter the course of the condition.

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