Microtubule-binding-region tau (MTBR-tau) present in cerebrospinal fluid (CSF) correlated strongly with tau pathology seen in PET imaging in the brains of people with Alzheimer's disease, they report.
"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," senior author Dr. Randall Bateman of Washington University School of Medicine in St. Louis, Missouri, said in a news release.
"As a physician, this information is invaluable in informing patient care, and in the future, to guide treatment decisions," he added.
The researchers used sequential immunoprecipitation and chemical extraction techniques followed by mass spectrometry to measure levels of various MTBR-tau species in spinal fluid of 100 older adults.
The cohort include 30 people with no cognitive impairment and no signs of Alzheimer's disease, 58 with amyloid plaques but no cognitive symptoms, or mild or moderate AD, and 12 with cognitive impairment caused by other conditions.
The researchers found that levels of the upstream region of MTBR residue 243-254 (MTBR-tau-243) were elevated in people with AD and the levels increased with more advanced cognitive impairment and dementia progression.
They confirmed their results by following 28 participants for two to nine years. Half of them had some degree of AD at the outset. Over time, MTBR-tau-243 levels rose significantly in those with AD, in step with a worsening of cognitive function.
Next the researchers compared the amount of tau visible on tau-PET brain scans with CSF MTBR-tau-243 levels in 20 study participants with AD and 15 without. They found that MTBR-tau-243 levels in CSF correlated highly with the amount of tau seen on the brain scans.
"Right now there is no biomarker that directly reflects brain tau pathology in cerebrospinal fluid or the blood," first author Dr. Kanta Horie said in the statement. It appears that MTBR-tau-243 "increases continuously as tau pathology progresses. This could be a way for us to not only diagnose Alzheimer's disease but tell where people are in the disease," she said.
"We also found some specific MTBR tau species in the space between neurons in the brain, which suggests that they may be involved in spreading tau tangles from one neuron to another. That finding opens up new windows for novel therapeutics for Alzheimer's disease based on targeting MTBR tau to stop the spread of tangles," Dr. Horie added.
This research had no commercial funding.
SOURCE: https://bit.ly/37yfipK Brain, online December 7, 2020.
By Reuters Staff
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