Highly Accurate Blood Test Diagnoses Alzheimer’s and Measures Dementia Progression

Several blood tests are currently available to assist doctors in diagnosing Alzheimer's disease in individuals experiencing cognitive symptoms. However, these tests do not provide insights into the clinical stage of the disease, such as the extent of memory or thinking impairment associated with Alzheimer's dementia. Since current treatments for Alzheimer’s are most effective during the early stages, a reliable method to assess the disease's progression could help physicians determine which patients would benefit from medications and to what degree. Now, a newly developed blood test not only aids in diagnosing Alzheimer's disease but also indicates the stage of progression and can help differentiate Alzheimer’s symptoms from those caused by other conditions.

In a new study, researchers from Washington University School of Medicine (St. Louis, MO, USA) and Lund University (Lund, Sweden) identified a protein called MTBR-tau243 in the blood, which accurately reflects the toxic accumulation of tau aggregates in the brain and correlates with the severity of Alzheimer’s disease. By analyzing blood levels of MTBR-tau243 from individuals with cognitive decline, the researchers were able to distinguish between early- and late-stage Alzheimer’s disease and differentiate Alzheimer’s patients from individuals whose symptoms were caused by other factors. Alzheimer’s disease involves the buildup of amyloid protein into plaques in the brain, followed by the development of tau protein tangles years later. Cognitive symptoms typically emerge when tau tangles become detectable, and these symptoms worsen as the tangles spread.

Previously, the researchers developed two blood tests that closely correlate with the amount of amyloid plaques in the brain, and these are now used by clinicians to assist with diagnosis. However, there was no blood test available to assess tau levels in the brain until now. In earlier studies, the team demonstrated that cerebrospinal fluid levels of MTBR-tau243 were closely linked to the presence of tau tangles in the brain. In their current study published in Nature Medicine, the team extended this analysis to blood. Blood samples are easier to collect compared to cerebrospinal fluid, which requires a spinal tap. The researchers developed a method to measure MTBR-tau243 levels in blood samples and compared these levels with the tau tangles detected in the brain through brain scans. Their analysis showed that blood MTBR-tau243 levels reflected the amount of tau tangles with 92% accuracy. In healthy individuals, MTBR-tau243 levels remained normal, regardless of amyloid plaque status, indicating that these levels do not change between asymptomatic individuals and those in the presymptomatic stage of Alzheimer’s disease with amyloid plaques.

Among individuals with cognitive symptoms due to Alzheimer’s disease, MTBR-tau243 levels were significantly higher in those with mild cognitive impairment and even more elevated—up to 200 times—among those in the dementia stage. These differences enabled clear differentiation between early- and late-stage Alzheimer’s disease. Furthermore, MTBR-tau243 levels were normal in individuals with cognitive symptoms caused by other forms of dementia, demonstrating that the test effectively distinguishes Alzheimer’s dementia from other conditions. Two FDA-approved therapies for Alzheimer’s disease work by lowering amyloid levels in the brain. With additional experimental drugs targeting tau and other aspects of Alzheimer's in development, the availability of blood tests to diagnose and stage the disease would allow doctors to tailor treatments to each patient’s specific condition.

“We’re about to enter the era of personalized medicine for Alzheimer’s disease,” said Kanta Horie, PhD, a research associate professor of neurology at WashU Medicine and co-first author. “For early stages with low tau tangles, anti-amyloid therapies could be more efficacious than in late stages. But after the onset of dementia with high tau tangles, anti-tau 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.”

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