Modern methods make it possible to detect Alzheimer's disease (the most common case of dementia) only "after the fact," when irreversible changes have already occurred in the brain and treatment is virtually ineffective. However, the first molecular signs signaling the development of this disease at the protein level begin to appear long before its manifestation, often 20 years in advance. A new method developed at the Ruhr-Universität in Bochum, Germany, can help detect Alzheimer's disease at a much earlier stage.
"The method should open up possibilities for early-stage therapies, when many drugs can still be effective," says Professor Klaus Gerwert of the Department of Biophysics at RUB.
In patients with Alzheimer's disease, amyloid beta-protein misfolds due to pathological changes long before the first symptoms appear. A team of researchers led by Klaus Herwerth has successfully diagnosed this abnormal formation using a simple blood test; as a result, the disease can be detected approximately eight years before the first clinical symptoms appear. However, the first version of this test was not suitable for clinical applications: it detected 71 percent of asymptomatic cases of Alzheimer's disease, but at the same time gave false-positive diagnoses to 9 percent of study participants. To increase the number of correctly identified cases of Alzheimer's disease and reduce the number of false-positive diagnoses, the researchers spent a lot of time and effort optimizing the test.
As a result, the researchers presented a two-level diagnostic method. First, a blood test is used to identify high-risk people.
Next, scientists add a dementia-specific biomarker, namely tau protein, to conduct further tests with those test participants who tested positive for Alzheimer's disease in the first step. If the second biomarker also tests positive, the likelihood of developing Alzheimer's disease is significantly increased. "By using the two-tier method, 87 out of 100 patients in our study were correctly diagnosed with Alzheimer's disease," Klaus Gerwert summarizes. "And we reduced the number of false-positive diagnoses in healthy people to 3 out of 100. The second assay uses cerebrospinal fluid."
"New clinical trials can now be conducted with participants in this experiment in the earliest stages of the disease," Gerwert notes. He hopes that existing therapies, which so far have had little effect, may produce results. "Two large, promising studies have recently failed, Crenezumab and Aducanumab, not least because it was probably too late by the time the therapy started. However, our results are encouraging.
The team is working in parallel to improve the technique for such analysis. While the first step is fully automatic, the tau-protein assay requires a puncture of the cerebrospinal fluid. Scientists, however, are confident that in the near future, tau protein can also be identified in a normal blood sample.
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