A newly developed blood test for Alzheimer’s disease not only assists in diagnosis but also provides critical information about the stage and severity of the condition, according to a study conducted by researchers at Washington University School of Medicine in St. Louis and Lund University in Sweden.
Although several blood tests for Alzheimer’s are already available, including two based on technology licensed from Washington University, these tests primarily help diagnose the disease in patients showing cognitive symptoms. However, they do not offer insight into the stage of the disease, particularly the extent of impairment in thinking or memory associated with Alzheimer’s dementia. Current therapies for Alzheimer’s are most effective in its early stages, making it crucial for doctors to gauge the progression of the disease. The new blood test not only measures the severity of Alzheimer’s but also helps distinguish it from other cognitive disorders.
The study, published on March 31 in Nature Medicine, reveals that blood levels of a protein called MTBR-tau243 can accurately reflect the amount of toxic tau protein accumulation in the brain. This accumulation correlates with the severity of Alzheimer’s disease. By analyzing MTBR-tau243 levels, researchers were able to differentiate between early- and later-stage Alzheimer’s and distinguish Alzheimer’s from other potential causes of cognitive decline.
“We currently lack easily accessible measures of Alzheimer’s tau tangles in clinical practice. This blood test provides a clearer indication of whether symptoms are due to Alzheimer’s, and it may also help doctors determine the most suitable treatments,” said Dr. Randall J. Bateman, co-senior author and Professor of Neurology at Washington University.
Tracking Alzheimer’s Disease Progression Through Blood
Alzheimer’s disease progresses with the buildup of amyloid plaques, followed by the formation of tau tangles in the brain. Cognitive symptoms emerge as tau tangles become detectable, worsening as the tangles spread. While positron emission tomography (PET) scans remain the gold standard for staging Alzheimer’s—providing detailed images of amyloid plaques and tau tangles—these scans are costly, time-consuming, and often unavailable outside major research centers.
Bateman’s team has developed blood tests as a more accessible alternative to brain scans. While their previous blood tests correlated closely with amyloid plaque buildup, no blood test had yet been developed to measure tau levels. In this new study, Bateman’s team extended their work by analyzing MTBR-tau243 levels in blood samples, comparing them to tau levels detected in brain scans.
The team conducted this analysis using two cohorts: 108 individuals from the Charles F. and Joanne Knight Alzheimer’s Disease Research Center at Washington University and 55 people from the Swedish BioFINDER-2 cohort. They validated their findings using an independent dataset of 739 people from the BioFINDER-2 cohort.
Participants spanned the full range of Alzheimer’s stages, from the presymptomatic phase (where amyloid plaques are present but symptoms have not yet appeared) to the late-stage dementia phase. For comparison, the study also included individuals with cognitive symptoms caused by other conditions.
The results were promising: blood levels of MTBR-tau243 reflected the amount of tau tangles in the brain with 92% accuracy. In people with no cognitive symptoms or those in the presymptomatic stage of Alzheimer’s, MTBR-tau243 levels were normal, regardless of amyloid status. However, among those with Alzheimer’s-related cognitive decline, MTBR-tau243 levels were significantly elevated, with those in the dementia phase showing up to 200 times higher levels than those in the mild cognitive impairment phase.
This test also proved effective in distinguishing Alzheimer’s from other forms of dementia, as MTBR-tau243 levels remained normal in people with cognitive symptoms caused by other diseases.
Personalized Treatment for Alzheimer’s Disease
The technology underlying this blood test has been licensed by Washington University to C2N Diagnostics, a startup that also developed the amyloid blood tests. These tests incorporate measurements of another tau variant, p-tau217.
“I believe that blood-based p-tau217 will be used to confirm an Alzheimer’s diagnosis, but MTBR-tau243 will be a valuable complement for both clinical and research purposes,” said Dr. Oskar Hansson, co-senior author and Professor of Neurology at Lund University. “When both biomarkers are positive, the likelihood that Alzheimer’s is the underlying cause of a person’s cognitive symptoms increases significantly, which is crucial for selecting the most appropriate treatment.”
Currently, two FDA-approved therapies aim to slow Alzheimer’s progression by targeting amyloid plaques, but several experimental drugs targeting tau or other aspects of Alzheimer’s are in development. As treatments evolve, blood tests that can diagnose and stage the disease will enable doctors to tailor treatments based on the patient’s specific disease state.
“We are entering the era of personalized medicine for Alzheimer’s disease,” said Dr. Kanta Horie, a researcher on the team. “With a clinically available blood test for staging and treatments targeting different disease stages, doctors will soon be able to optimize care for each patient’s needs.”
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