Researchers suggest an Alzheimer’s protein can help doctors stage the disease

Scientists have discovered that a novel form of an Alzheimer’s protein, which is found in the fluid that surrounds the brain and spinal cord, can indicate what stage of the disease a person is suffering from.

Medical professionals can use tangles of the Alzheimer’s protein, named tau, to track the progress of Alzheimer’s in the human body, according to a study from researchers at Washington University School of Medicine in St. Louis, USA. Tau tangles are thought to be toxic to neurons, and their spread through the brain foretells the death of brain tissue and cognitive decline. Tangles appear as the early, asymptomatic stage of Alzheimer’s develops into the symptomatic stage.

The discovery of microtubule binding region tau (MTBR tau) in the cerebrospinal fluid could lead to a way to diagnose people in the earliest stages of Alzheimer’s disease, before they have symptoms or when their symptoms are still mild and easily misdiagnosed. It also could accelerate efforts to find treatments for the devastating disease, by providing a relatively simple way to gauge whether an experimental treatment slows or stops the spread of toxic tangles.

Senior author Randall J Bateman, a professor of Neurology, treats patients with Alzheimer’s disease on the Washington University Medical Campus. Bateman said: “This MTBR tau fluid biomarker measures tau that makes up tangles and can confirm the stage of Alzheimer’s disease by indicating how much tau pathology is in the brains of Alzheimer’s disease patients.

“If we can translate this into the clinic, we’d have a way of knowing whether a person’s symptoms are due to tau pathology in Alzheimer’s disease and where they are in the disease course, without needing to do a brain scan. As a physician, this information is invaluable in informing patient care, and in the future, to guide treatment decisions.”

Tau tangles can be detected by positron emission tomography (PET) brain scans; however, brain scans are time-consuming and expensive. The team from Washington University are developing diagnostic blood tests for Alzheimer’s disease based on amyloid or a different form of tau, but neither test can pin down the amount of tau tangles across the stages of disease.

Bateman and first author Kanta Horie, PhD, a visiting scientist in Bateman’s lab, discovered that specific MTBR tau species were enriched in the brains of people with Alzheimer’s disease, and that measuring levels of the species in the cerebrospinal fluid that bathes the brain might be a way to gauge how broadly the toxic tangles have spread through the brain. Horie and colleagues have developed a new method based on using chemicals to purify tau out of a solution, followed by mass spectrometry.

Using this technique, Horie, Bateman and colleagues analysed 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 caused by other conditions. The researchers found that levels of a specific form – MTBR tau 243 – in the cerebrospinal fluid were elevated in the people with Alzheimer’s and that  the more advanced a person’s cognitive impairment and dementia were, the more it increased.

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