Blood test offers insight into Alzheimer’s stage and severity

A newly developed blood test for Alzheimer’s disease not only helps with the diagnosis of the neurodegenerative disorder, but also indicates how far it is advanced, according to a study by researchers at Washington University School of Medicine in St. Louis and Lund University in Sweden.

Different blood tests for Alzheimer’s disease are already clinically available, including two based on technology that has a license from Washu. Such tests help doctors diagnose the disease in people with cognitive symptoms, but do not indicate the clinical stage of disease symptoms – that is, the degree of damage to thinking or memory as a result of the dementia of Alzheimer’s. The current therapies of Alzheimer’s are most effective in early stages of the disease, so having a relatively simple and reliable way to measure the extent that the disease is advanced, doctors can help determine which patients are likely to benefit from the treatment of medicines and to what extent. The new test can also provide insight into whether the symptoms of a person are probably due to Alzheimer’s versus another cause.

The study was published on March 31 in Nature Medicine.

In the study, the researchers found that levels of a protein called MTBR-TAU243 accurately reflect and correlate the amount of toxic accumulation of Tau aggregates in the brain with the severity of Alzheimer’s disease. The researchers analyze the blood levels of MTBR-TAU243 of a group of people with cognitive decline, the researchers could distinguish between people with an early or later stage of Alzheimer’s Alzheimer’s and divorced both groups of Alzheimer’s patients whose symptoms were caused by something other than Alzheimer’s disease.

This blood test clearly identifies Alzheimer’s Tau tau, which is our best biomarker -for the symptoms and dementia of Alzheimer. In clinical practice, we currently have no easy or accessible measures of the tangles and dementia of Alzheimer’s, and so a devoured blood test as these can give a much better indication if the symptoms are due to the Alzheimer’s and doctors can also help decide which treatments are best for their patients. “

Randall J. Bateman, MD, Co-Senior Author, De Charles F. and Joanne Knight Distinguished Professor of Neurology at Washu Medicine

Following Alzheimer’s disease progression from blood

Alzheimer’s disease comprises a structure of a protein, called amyloid, in plaques in the brain, followed by the development of tau protein years later. Cognitive symptoms arise around the time that Tau tangles become detectable and the symptoms worsen as the tangles spread. The gold standard for organizing Alzheimer’s disease is positronemissietoMography (PET) brain scans for amyloid plaques and tau tangs. Amyloid scans provide information about the presymptomatic and early symptomatic stages, while Tau scans are useful for following later stages of the disease. PET brain scans are very accurate but expensive, time -consuming and often not available outside large research centers, so that they are not used much.

Bateman leads a team that develops blood tests for Alzheimer’s disease as a more accessible alternative to brain scans. They have developed two blood tests that are closely related to the amount of amyloid plaques in the brain. Both are now used by doctors to support the diagnosis. But so far there has been no blood test that reports about Tau levels in the brain.

In an earlier study, Bateman and colleagues, including co-first authors Kanta Horie, PhD, a research professor of Neurology at Washu Medicine, and Gemma Salvadó, PhD, then a postdoctoral researcher at Lund University, and a partner of the Lund-University of Lund-Honespinne-spinal Toon-Thande-Tau-TaRspinal MTBR-TAU243 showed. Correler closely with Tau tangs in the brain. In the current study, the team expanded the analysis of blood. A blood sample is easier to collect than cerebrospinal liquid, which is obtained through a spinal tap.

The researchers developed a technique to measure MTBR-TAU243 levels in people’s blood and compared it with the amount of tau tangs in their brains as measured by brain scans. They sent the approach to data from two cohorts: volunteers at Charles F. van Washu Medicine and Joanne Knight Alzheimer Disease Research Center, including 108 people, and a subset of 55 people from the Swedish Biofinder-2-Cohort. To assess whether the approach was generalizable, they validated it in an independent data set consisting of the remaining 739 people in the Biofinder-2-Cohort.

The people in the two cohorts represented anything but the most serious end of the spectrum of Alzheimer’s disease, from the presymptomatic stage in which the amyloid levels of the brain are raised but people remain cognitively healthy, due to medical expenses with mild cognitive disorders, to late symptomatic, for late symptomatic disease, for late symptomatic disease, for late symptomatic disease, for late symptomatic disease, for late symptomatic disease, for late symptomatic disease, for late symptomatic disease, Late Symptomatic disease, Late Symptomatic disease, Late Symptomatic disease, Late Symptomatic disease, Late symptomatic disease, Late Symptomatic disease, Late Symptomatic Disease Late. Symptomatic disease, to late symptomatic disease. For comparison, cognitively healthy people with normal amyloid levels and people with cognitive symptoms due to disorders other than Alzheimer’s disease were admitted.

The researchers’ analysis showed that the MTBR-TAU243 levels of blood reflected the amount of tau tables in the brain by 92% accuracy. MTBR-TAU243 levels in the blood were normal in asymptomatic people, regardless of amyloid status, which means that blood mtbr-tau243 levels do not change between healthy people and people in the presymptomatic stage of Alzheimer’s disease with amyloid plaques.

Among people with cognitive symptoms as a result of Alzheimer’s disease, MTBR -TAU243 -levels were considerably increased for people in the mild cognitive disorder phase of Alzheimer’s disease and much higher to 200 times -for those in the dementation phase. These differences translated into a clear separation of people in Alzheimer’s disease in the early and late stage. At the same time, MTBR-TAU243 levels were normal in people with cognitive symptoms due to diseases other than Alzheimer’s, which means that the test effectively distinguished the dementia of Alzheimer’s from other types of dementia.

The technology that underlies the blood test for TAU aggregates has a permit from Washu to C2N Diagnostics, a Washu startup that has developed the blood tests for amyloid. These amyloid tests contain measurements of another form of Tau called P-TAU217.

“I believe that we will use P-TAU217 on blood base to determine whether a person has Alzheimer’s disease, but MTBR-TAU243 will be a very valuable addition to both clinical environments and research tests,” Hansson said. “When both biomarkers are positive, the chance that Alzheimer’s is the underlying cause of the cognitive symptoms of a person increases considerably, compared to when only P-TAU217 is abnormal. This distinction is crucial for selecting the most suitable treatment for each patient.”

Blood tests can inform personalized Alzheimer’s treatment

Two Alzheimer’s therapies are approved by the Food and Drug Administration (FDA) to slow down the progression of the disease, and both work by lowering amyloid levels in the brain. Horie said that the number and variety of available medicines from Alzheimer’s can soon expand, because various experimental medicines that focus on Tau or other aspects of Alzheimer’s disease in the pipeline. With blood tests to diagnose the disease and stage, doctors could adapt treatments to the specific disease condition of the patient.

“We are about to enter the era of personalized medicine for Alzheimer’s disease,” said Horie. “For early stages with low tau tangles, anti-amyloid therapies could be more effective than in late stages. But after the start of dementia with high Tau tangles, anti-Tau therapy or one of the many other experimental approaches can be more effective. As soon as we have a clinically available blood test, the work will be with different staging.”