New Blood Test for Alzheimer’s Diagnosis

Assay detects misfolded amyloid-beta peptides in early disease

Researchers in Germany have developed a blood test that may allow the detection of Alzheimer’s disease (AD) at an early stage. The test consists of an immunochemical analysis using an infrared sensor. The sensor’s surface is coated with antibodies that extract biomarkers for AD from blood or cerebrospinal fluid. The infrared sensor analyzes the biomarkers for pathologic changes, which can develop more than 15 years before the clinical symptoms of AD appear. The new method was described in the journal Analytical Chemistry.

A major problem in the diagnosis of AD is the fact that, by the time the first clinical symptoms appear, irreversible damage to the brain has already occurred. At that point, symptomatic treatment is the only available option. “If we wish to have a drug at our disposal that can significantly inhibit the progress of the disease, we need blood tests that detect Alzheimer’s in its pre-dementia stages,” said lead investigator Professor Dr. Klaus Gerwert, head of the Department of Biophysics at Ruhr University.

In the new test, the secondary structure of amyloid-beta peptides serves as the biomarker. This structure changes in AD patients. As the disease progresses, more and more misfolded amyloid-beta peptides accumulate, gradually forming visible plaque deposits in the brain––the hallmark of AD. Pathological amyloid-beta plaques may be temporarily detected by positron emission tomography, Gerwert said, but this procedure is comparatively expensive and involves radiation exposure.

Gerwert and his colleagues developed an infrared sensor that detects misfolded amyloid- beta peptides. The sensor extracts the peptides from body fluids. After initially working with cerebrospinal fluid, the researchers expanded the method to include blood analysis.

Currently, amyloid-beta peptides may be analyzed using the enzyme-linked immunosorbent assay (ELISA), which can identify the total concentration of peptides as well as the concentration of individual conformations in body fluids. But the ELISA test does not provide information on the diagnostically relevant distribution of secondary structures. “This is why ELISA tests have not been proven very effective when applied in blood sample analysis in practice,” Gerwert explained.

Using the new method, the researchers analyzed samples from 141 patients. They reported a diagnostic precision of 84% in blood and 90% in cerebrospinal fluid. The test revealed an increase in misfolded amyloid-beta biomarkers, indicating the presence of AD.

Source: EurekAlert (link is external); March 15, 2016.

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