A group of German researchers is close to developing a blood test that can detect Alzheimer’s disease long before symptoms begin to appear. This new test will be extremely useful for scientists trying to understand and treat the disease, as one of the main problems hampering Alzheimer’s research is that the disease is always detected at a relatively late stage.
The cause: Symptoms develop slowly over several years and become obvious long after the disease has already made changes to the brain.
There is no simple way to detect whether Alzheimer’s disease is developing in an individual. The only reliable methods of diagnosis are positron emission tomography, which is time-consuming and quite expensive, and analysis of cerebrospinal fluid which is performed by lumbar puncture and is very painful and invasive.
One of the hallmarks of Alzheimer’s disease is an abnormal accumulation of amyloid beta plaques in the brain. Amyloid beta is present in the healthy brain, but in people with Alzheimer’s, the protein folds incorrectly and accumulates. In this form, it is toxic to neurons. And these amyloid plaques can begin to develop 15 to 20 years before symptoms of the disease appear.
The researchers, led by Klaus Gerwert, wanted to know whether measuring the relative levels of healthy and pathological beta amyloid in the blood could identify Alzheimer’s in its early stages.
The blood test works with immuno-infrared sensor technology; Based on an antibody, the sensor extracts all beta amyloid from the blood sample. The two versions of beta-amyloid absorb infrared light at different frequencies, allowing researchers to measure the relative levels of healthy and unhealthy protein.
Unlike other methods, the immuno-infrared sensor does not provide a precise amount of misfolded protein; rather, it provides information on the ratio between healthy and unhealthy versions . This is beneficial as it is less affected by natural fluctuations in blood protein levels.
To investigate whether the test worked, the team of scientists at Ruhr Bochum University (Germany) used data from the Swedish BioFINDER cohort, a study carried out by Oskar Hansson of Lund University (Sweden).
The results were encouraging: In individuals who showed early and subtle symptoms of Alzheimer’s, the test detected changes in beta-amyloid levels that were associated with abnormal deposits visualized by brain scans. In other words, the test detected an increase in the levels of beta-amyloid plaques, later confirmed by a brain scan.
The next step was to see if abnormal beta-amyloid levels could be detected before Alzheimer’s symptoms developed. To do this, they took data from the ESTHER cohort study. They evaluated blood samples from 65 people who later developed Alzheimer’s disease. These blood samples were compared to 809 individuals who did not develop the disease.
On average, the blood test could detect Alzheimer’s disease 8 years before clinical symptoms became apparent.
The test correctly diagnosed Alzheimer’s in 70% of the cases and wrongly predicted that 9% would develop the disease. Overall, the diagnostic accuracy was 86%.
Compared to a lumbar puncture or PET scan, a simple blood test would be much more useful for doctors and researchers alike. Although the test is not perfect yet, it would be a useful way to identify those who may be at risk of developing Alzheimer’s before sending them off for further investigation.
Reference: Amyloid blood biomarker detects Alzheimer’s disease. Andreas Nabers, Laura Perna, Julia Lange, Ute Mons, Jonas Schartner, Jörn Güldenhaupt, Kai ‐ Uwe Saum, Shorena Janelidze, Bernd Holleczek, Dan Rujescu, Oskar Hansson, Gerwert, Hermann Brenner. DOI 10.15252 / emmm.201708763 | EMBO Molecular Medicine (2018)
