Finding forgetting in the blood – new dementia test?

Alzheimer’s diagnosis Finding forgetting in the blood – new dementia test?

29.09.2021Editor: Christian Lüttmann

A blood test could reveal even more about the state of health in the future. In a pilot study, Empa researchers have shown that a blood sample can be used to determine whether a patient is suffering from the onset of dementia. To do this, they used atomic force microscopy to detect protein deposits on the blood cells.

St. Gallen / Switzerland – When does inattention and forgetting turn into a serious illness? In the case of Alzheimer’s, it is often difficult to recognize the creeping process of the disease at an early stage and to take appropriate action. Until the first suspicion is clear, those affected have to be prepared for lengthy and complex procedures. A team from Empa and the St. Gallen Cantonal Hospital is now developing a blood test that will enable diagnosis using atomic force microscopy (AFM).

Capture proteins in their actual form

In the beginning, for the physicist Dr. Peter Nirmalraj’s desire to understand Alzheimer’s disease in order to enable new approaches in diagnostics and therapy. It would be a step further if the exact role of beta-amyloid peptides and tau proteins, which are associated with neurodegenerative disease and are associated with the formation of so-called plaques, were deciphered. Nirmalraj had therefore resolved not only to register the mere presence of the suspicious proteins, but also to determine their changeable shape and form as well as their number.

Common methods make it possible to determine the total amount of both proteins in body fluids. However, these techniques do not allow differences in the shape and condition of the protein accumulations to be made visible. The researcher is therefore working on technologies that enable observations in the nanometer range in blood while preserving the structure and morphology of the proteins.

Together with neurologists at the St. Gallen Cantonal Hospital, Nirmalraj has now completed an initial study. For the pilot study, he examined blood samples from 50 patients and 16 healthy test subjects. Using atomic force microscopy, the Empa researcher analyzed the surface of around 1,000 red blood cells per person without knowing any information about their state of health. “This was the only way to guarantee that the interpretation of the data remained objective,” says Nirmalraj.

Hairy blood cells

The Empa researcher measured the size, structure and nature of protein accumulations that were on the blood cells. After thousands of red blood cells, the team eagerly awaited the comparison of the results from Nirmalraj’s counts with the clinical data of the neurologists. And indeed, the researchers recognized a pattern that fits the test subjects’ stage of disease: people with Alzheimer’s disease had large amounts of protein fibers made from beta-amyloid peptides and tau proteins. The proteins were able to join together to form fibers several hundred nanometers in length. In healthy people or those with incipient brain disorders, however, Nirmalraj counted only a few fibers.

This has proven the feasibility of a blood analysis using AFM technology, as the Empa researcher says. This would have clear advantages for the diagnosis. “If a reliable blood test can be developed with this method, people with suspected Alzheimer’s would be spared the uncomfortable puncture of the spinal canal in order to be able to diagnose the disease clearly,” Nirmalraj gives an example.

However, there is still a long way to go before a simple blood test is available from the doctor. Next, the team wants to corroborate the data by examining a larger number of subjects at various stages of the disease using AFM and chemical analysis.

Originalpublikation: PN Nirmalraj, T Schneider, A Felbecker: Spatial organization of protein aggregates on red blood cells as physical biomarkers of Alzheimer’s disease pathology, Science Advances (2021), Vol 7, Issue 39; DOI: 10.1126/sciadv.abj2137

(ID:47697935)

–