Research groups at the Halle University Medical Department and the Ulm University Neurology Clinic have identified the protein “beta-synuclein” as a candidate for early diagnosis of Alzheimer’s disease. In research conducted in cooperation with the Germany-wide FTLD Consortium, the latest results underline the potential of beta-synuclein for early detection of Alzheimer’s disease. The data shows a clear correlation between the beta-synuclein concentration in the blood and structural changes in certain areas of the brain. The method developed especially for this purpose is minimally invasive and allows physicians to distinguish between Alzheimer’s disease and other forms of dementia. The latest findings were published in the reputable journal “Alzheimer’s & Dementia”.

In 2021, there were about 1.8 million people suffering from dementia in Germany, of which Alzheimer’s disease was the cause in about 60 per cent of the cases. In order to enable an early and clear diagnosis, researchers are currently urgently searching for new biomarkers. Up to now, the early diagnosis of neurodegenerative diseases has been restricted to the detection of certain proteins in the cerebrospinal fluid that collect in the brain before the first symptoms appear. However, it is not possible to clearly distinguish between Alzheimer’s disease and other forms of dementia. At an advanced stage of the disease, when massive cognitive impairments are already present, a loss of brain mass also becomes evident.

“Beta-synuclein is a pre-synaptic protein, i.e. a component of the nerve endings”, explains Professor Markus Otto, director of the University Clinic and Polyclinic for Neurology at the Halle University Medical Centre. The research teams from Halle and Ulm, in cooperation with their partners in Italy, have only recently been able to prove that the concentration of beta-synuclein in the cerebrospinal fluid is elevated at an early stage in a case of Alzheimer’s disease. “It was already assumed that the changes found on these nerve endings in the brain were related to the memory disorder. Thus, we focused on finding evidence of this in the blood. Based on our results, we suspect that the first signs of Alzheimer’s are structural changes to the synapses”.

Germany-wide consortium delivered the necessary data in recent study

In order to find out whether beta-synuclein is suitable as a potential new biomarker, however, further data and larger test groups were necessary. A total of 374 patients from the Research Consortium of Frontotemporal Lobar Degeneration (FTLD) network provided the basis for the recent study. These included 31 cognitively healthy people, 74 Alzheimer’s patients and 269 patients with other forms of dementia. While Alzheimer’s typically results in the loss of brain mass (atrophy) in the temporal lobe, other forms of dementia affect the areas of the frontal lobe. The researchers assessed cognitive performance among the subjects and determined the volume of the brain regions using MRI scans. The results were then compared with blood concentrations of various biomarkers.

“Here, it became evident that there is a very good correlation between the atrophy patterns in the temporal lobe typical to Alzheimer’s disease and the increase in the concentration of the protein beta-synuclein in the blood”, says Professor Otto, who is also the spokesperson for the FTLD research consortium in Germany. “The biomarkers used up to now have not shown this correlation to the temporal lobe in the early course of the disease. The results can already be put into practice. In our network, we visit patients once a year and examine the progression of the disease. This has already made it possible for us to make an early diagnosis in some cases, which we are currently monitoring”.

Blood samples instead of cerebrospinal fluid and lumbar punctures

“In order to assess dementia-related illnesses, it is essential to examine the entire range of available biomarkers. Beta-synuclein is a valuable addition and could enable a diagnosis before the depletion of synapses has reached full speed”, explains PD Dr Patrick Öckl, head of the research group at the Ulm University Neurology Clinic. With enough prior warning, treatments would be conceivable that would make it possible to better control Alzheimer’s disease. The big advantage of beta-synuclein, in comparison to established biomarkers, is that this protein can also be detected in a blood sample by means of a specifically developed and highly sensitive method. This makes the examination much more comfortable for affected patients. “In order to be able to rely on examining blood samples rather than taking cerebrospinal fluid through lumbar puncture, we need mass spectrometers” says Öckl. Therefore, there is only a small number of labs in which the procedure can be performed. “We are currently working on making the new method routine”. There is also non-neurodegenerative damage linked to the loss of nerve connections, for example following strokes or brain trauma, and it could be possible to make a diagnosis in such cases as well.

The nationwide German Research Consortium of Frontotemporal Lobar Degeneration (FTLD) is a conglomeration of 15 university hospitals (Halle/Saale, Ulm, Bonn, Erlangen, Göttingen, Hamburg, Homburg/Saar, Mannheim, LMU Munich, TU Munich, Münster, Rostock, Tübingen, Würzburg -neurology and psychiatry) and the Max Planck Institute for Human Cognitive and Brain Sciences in Leipzig.

Literature:
Oeckl P, Anderl-Straub S, Danek A, et al. Relationship of serum beta-synuclein with blood biomarkers and brain atrophy. Alzheimer’s Dement. 2022;1-14. https://doi.org/10.1002/alz.12790

Text: Halle University Medical Department, Jonas Machner
Translation: Kate Gaugler