A new form of Alzheimer’s disease found in the cerebrospinal fluid indicates the stage of the disease

A new form of Alzheimer’s disease in the fluids surrounding the brain and spinal cord, according to a study by researchers at the University of Washington, indicates at what stage of the disease a person is and tracks tau protein tangles in the brain. Of medicine. Tau tangles are thought to be toxic to neurons, and their spread through the brain heralds death of brain tissue and diminished cognitive function. Tangles appear as the early asymptomatic stage of Alzheimer’s disease develops into the symptomatic stage.

The discovery of so-called microtubule junction tau (MTBR tau) in cerebrospinal fluid leads to a way to diagnose people in the early stages of Alzheimer’s disease before symptoms appear or when symptoms are still mild and misdiagnosed. There is a possibility. It may also accelerate efforts to find cures for catastrophic diseases by providing a relatively easy way to measure whether treatment slows or stops the spread of toxic tangles.

This study was published in Brain on December 7th.

“This MTBR tau fluid biomarker can identify the stage of Alzheimer’s disease by measuring the tau that makes up the tangle and showing how much tau lesions are in the brain of patients with Alzheimer’s disease,” said the senior author. Says. Randall J. Bateman, MD, Charles F. and Joan Knight, a prominent professor of neurology. Bateman is treating patients with Alzheimer’s disease on the University of Washington’s medical campus. “If we can translate this into a clinic, there is a way to know if a person’s symptoms are due to the tau pathology of Alzheimer’s disease and where they are in the course of the disease, without having to do a brain scan. Is invaluable in providing information to patient care and in guiding treatment decisions in the future. “

Alzheimer’s disease begins when a protein in the brain called amyloid begins to form spots in the brain. During this amyloid stage, which can last for more than 20 years, people show no signs of cognitive decline. However, shortly after tau tangles began to spread to neurons, people began to show confusion and amnesia, and brain scans showed increased atrophy of brain tissue.

Tau tangles can be detected by positron emission tomography (PET) brain scans, but brain scans are time consuming, costly, and not available everywhere. Bateman and colleagues are developing a diagnostic blood test for Alzheimer’s disease. Amyloid Or another Tau shapeHowever, neither test can determine the amount of tau entanglement throughout the stage of the disease.

MTBR tau is an insoluble portion of tau protein and is the main component of tau tangles. Bateman and his first author, Cantaholly, a visiting scientist in Bateman’s lab, found that certain MTBR tau species are abundant in the brains of people with Alzheimer’s disease and in the cerebrospinal fluid that soaks the brain. I realized that measuring species levels could be a way to measure how toxic tangles are spread throughout the brain. Previous researchers who used antibodies to tau could not detect MTBR tau in cerebrospinal fluid. However, Horie et al. Have developed a new method based on the purification of tau from solution using chemicals followed by mass spectrometry.

Using this technique, Horie, Bateman and colleagues analyzed the cerebrospinal fluid of 100 people in their 70s. Thirty had no cognitive impairment or signs of Alzheimer’s disease. Fifty-eight had amyloid plaques with no cognitive symptoms or mild or moderate Alzheimer’s disease. And 12 had cognitive deficits caused by other conditions. Researchers have found that levels of a particular form (MTBR tau 243) in cerebrospinal fluid are elevated in people with Alzheimer’s disease, which increases as human cognitive impairment and dementia progress. ..

The researchers validated the results by following 28 members of the original group for 2-9 years. Half of the participants had some degree of Alzheimer’s disease at the beginning of the study. Over time, MTBR tau 243 levels increased significantly in the Alzheimer’s disease group, in step with worsening scores on cognitive function tests.

The gold standard for measuring tau in the living brain is the tau-PET brain scan. The amount of tau seen on a brain scan correlates with cognitive impairment. To see how their technique fits the gold standard, researchers compared the amount of tau seen in 35 brain scans – 20 with Alzheimer’s disease and 15 without – cerebrospinal fluid. Level of MTBR tau 243 in liquid. MTBR tau 243 levels are highly correlated with the amount of tau identified by brain scans, suggesting that their technique accurately measured the amount of tau, or damage, accumulated in the brain.

“Currently, there are no biomarkers that directly reflect the pathology of cerebrospinal fluid or brain tau in the blood,” Horie said. “What we have found here is that as the pathology of tau progresses, a new form of tau, MTBR tau 243, continues to increase. This not only allows us to diagnose Alzheimer’s disease. It may be a way for people to know where they are sick. Also, some specific MTBR tau species have been found in the space between neurons in the brain, which separates them from one neuron. It suggests that it may be involved in the spread of tau entanglement in neurons. The finding suggests a new treatment for Alzheimer’s disease based on targeting MTBR tau and stopping its spread. Open a new window. “