A novel blood test that detects a key biomarker for Alzheimer’s disease (AD) could help physicians more accurately determine the presence and track disease progression.
The test measures levels of the protein MTBR-tau243 — microtubule-binding region of tau containing the residue 243 — a biomarker of tau tangles in the brain that may be a more accurate measure of tau pathology than other established biomarkers.
Investigators used the test to successfully distinguish between patients at different stages of AD progression and identify whether cognitive decline was likely due to AD or some other cause.
“This blood test clearly identifies Alzheimer’s tau tangles, which is our best biomarker measure of Alzheimer’s symptoms and dementia,” study investigator Randall J. Bateman, MD, professor of neurology at Washington University School of Medicine, St. Louis, said in a press release.
“In clinical practice right now, we don’t have easy or accessible measures of Alzheimer’s tangles and dementia, and so a tangle blood test like this can provide a much better indication if the symptoms are due to Alzheimer’s and may also help doctors decide which treatments are best for their patients,” he added.
The research was published online on Nature Medicine and reported in Medscape News.
AD can be confirmed clinically through identification of tau pathology using tau PET, but researchers said a more accessible test is needed for clinical practice. Fluid biomarkers are an attractive alternative because of their accessibility and affordability, investigators noted.
Bateman and his colleagues have developed two other blood tests for AD that identify amyloid plaques in the brain. But there currently are no blood tests that measure tau in the brain.
Building on findings presented at the 2023 Clinical Trials on Alzheimer’s Disease (CTAD) conference, investigators measured plasma MTBR-tau243 levels in individuals in the Swedish BioFINDER-2 cohort (n = 108) and the Charles F. and Joanne Knight Alzheimer Disease Research Center cohort (n = 55). They used a larger cohort from Swedish BioFINDER-2 (n = 739) to validate the results.
Across all three groups, which consisted of patients at every stage of AD, there were elevated plasma MTBR-tau243 levels that increased as the level of dementia increased. Plasma MTBR-tau243 itself also carried a strong and linear correlation with tau PET in areas of the brain with intermediate (P < .001) and late tau accumulation (P < .001) compared with two other known biomarkers, p-tau217 and p-tau205.
“I believe we will use blood-based p-tau217 to determine whether an individual has Alzheimer’s disease, but MTBR-tau243 will be a highly valuable complement in both clinical settings and research trials,” Co-senior Author Oskar Hansson, MD, PhD, a professor of neurology at Lund University in Lund, Sweden, said in the press release.
“When both of these biomarkers are positive, the likelihood that Alzheimer’s is the underlying cause of a person’s cognitive symptoms increases significantly, compared to when only p-tau217 is abnormal. This distinction is crucial for selecting the most appropriate treatment for each patient,” Hansson added.
Accurate disease staging could help clinicians select the most appropriate therapies for their patients, investigators noted.
“For early stages with low tau tangles, anti-amyloid therapies could be more efficacious than in late stages,” Kanta Horie, PhD, co-author and researcher at WashU Medicine, said in the press release. “But after the onset of dementia with high tau tangles, antitau therapy or one of the many other experimental approaches may be more effective.”
“Once we have a clinically available blood test for staging, plus treatments that work at different stages of the disease, doctors will be able to optimize their treatment plans for the specific needs of each patient,” he added.
The technology has been licensed to C2N Diagnostics, which was cofounded by Bateman and study co-author David Holtzman, MD, Washington University School of Medicine. The company plans to make the test available before the end of the year, Horie said.
Research, Clinical Implications
Commenting, Gregory S. Day, MD, associate professor of neurology at the Mayo Clinic College of Medicine, who was not involved with the research said the results are another step toward noninvasive biomarkers for AD that are accessible and assess neuropathologic change.
“MTBR-tau243 offers particularly promise for detecting, and potentially even tracking, tau neuropathology in our research participants, with clear implications for staging disease for clinical trials,” he said.
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