A “heat map” of the brain of a person with mild Alzheimer’s dementia shows where high-density protein is stored in red and orange and low-density protein in green and blue. Researchers at the Washington University School of Medicine in St. Louis have discovered a form of spinal fluid lock that monitors the brain with a clapping of the hands and indicates the stage of the disease. Credit: Tammy Benzinger / Knight ADRC
Discovery can lead to better diagnostics, making quicker efforts to find a cure.
A novel form Alzheimer’s According to research by researchers at the Washington University School of Medicine and Medicine in St. Louis, fluids around the brain and spinal cord are found to indicate what stage of the disease a person is in, and track the formation of Tau protein in the brain. . Tangles are thought to be toxic to neurons, and their spread through the brain predicts the death of brain tissue and cognitive decline. The early, asymptomatic stage of Alzheimer’s appears to be congenital as it develops into the signaling stage.
The discovery of the so-called microtubule binding region tau (cerebrospinal fluid) in the cerebrospinal fluid can lead to a way to diagnose people in the early stages of Alzheimer’s disease, when they have symptoms before or when their symptoms are still mild and easily misdiagnosed. It can also speed up efforts to find a cure for a devastating disease, check if an experimental treatment slows down or prevents the spread of toxic clots.
The study is published in the journal Today (December 7, 2020) The brain.
Charles F., senior author of M.D., Randall J. “This MTBR traumatic fluid biomarker is tormenting and can confirm the stage of Alzheimer’s disease by indicating how much pathology is present in the brains of Alzheimer’s patients,” Batman said. And Joanna Knight Special Professor of Neurology. Batman treats Alzheimer’s patients on Washington University Medical Campus. “If we can translate this into a clinic, we have a way of knowing if a person’s symptoms are due to Alzheimer’s disease pathology and where they are in the course of the disease, without the need for a brain scan. As a physician, this information is invaluable in informing patient care and, in the future, guiding treatment decisions. “
Alzheimer’s begins when a brain protein called amyloid begins to form plaques in the brain. During this amyloid phase, which can last for two decades or more, people show no signs of cognitive decline. However, as soon as the tau clot spreads in neurons, people begin to exhibit confusion and memory loss, and brain scans show increased absorption of brain tissue.
Tungles can be detected by a citron emission tomography (PET) brain scan, but brain scans are time consuming, expensive and not available everywhere. Batman and colleagues are developing diagnostic blood tests for Alzheimer’s disease based on different types of amyloid or tau, but neither test will be able to reduce the amount of tai tangles in the disease stage.
MTBR tau is an insoluble part of tau protein and is the primary component of tau tangles. Scientist Batman and first author Kanta Hori, who visited Batman’s laboratory, realized that certain MTBR tai strains had been enriched in the brains of people with Alzheimer’s disease, and that the cerebrospinal fluid bathing the brain could contain a measured level of species. How to estimate how widely spread toxins from the brain. Previous researchers had failed to detect MTBR floors in cerebrospinal fluid using antibodies against palms. But Hori and his colleagues developed a new method of purifying tau based on the use of chemicals, followed by mass spectrometry.
Using this technique, Hori, Batman and colleagues analyzed cerebrospinal fluid from 100 people in their 70s. Thirty had no cognitive impairment and no signs of Alzheimer’s; 58 had amyloid plaques with no cognitive symptoms, or with mild or moderate Alzheimer’s dementia; And 12 had cognitive impairment due to other conditions. The researchers found that certain levels of MTBR T24 243 – cerebrospinal fluid were elevated in people with Alzheimer’s and that the person’s cognitive impairment and dementia were more advanced.
Researchers followed 28 members of the original group over two to nine years to verify their results. Half of the participants had a slight degree of Alzheimer’s at the beginning of the study. Over time, levels of MTBR T24 243 in the Alzheimer’s disease group increased significantly, in a step leading to an increase in scores on cognitive function tests.
The gold standard for measuring tau in the living brain is the tau-PET brain scan. The amount of rhythm seen in a brain scan is related to cognitive impairment. To see how their technique matched the gold standard, the researchers compared the amount of visible TU in a brain scan to 35 TU – 20 with Alzheimer’s and 15 without – with levels of MTBR T 243 in cerebrospinal fluid. The MTBR T24 243 levels were very consistent with the amount of tau known in brain scans, indicating that their technique accurately measures how much tau – and therefore damage – to the brain.
“Right now there is no biomarker that reflects fresh pathology of the brain into cerebrospinal fluid or blood,” Hori said. “What we have found here is that the latest form of TAT, MTBR DAT 243, is constantly increasing with the progress of TAT pathology. This can be a way not only to diagnose Alzheimer’s disease, but also to tell people where the disease is. We have also found some specific MTBR Tau species in the space between neurons in the brain, suggesting that they may be involved in spreading the T-clot from one neuron to another. The discovery has opened new windows of novel therapeutic for Alzheimer’s disease based on targeting MTBR to prevent the spread of arthritis. “
Reference: “CSF Tau Microtubule Binding Field, Identifies the Stress Complications and Clinical Stages of Alzheimer’s Disease” by Kanta Hori, Nicholas R. Barthalami, Chihiro Sato and Randall J. Batman, 7 December 2020, The brain.
DOI: 10.1093 / brain / av a37373
