Beta-synuclein: An indicator of the loss of synapses in Alzheimer's disease
Beta-synuclein is a so-called synaptic protein. It occurs in the brain at the junction between two nerve cells—at this synapse, the chemical transmission of stimuli takes place. The many millions of nerve cells in the brain pass on information in this way. Beta-synuclein is involved in the function of the synapses.
In Alzheimer's dementia, more and more nerve cells fail, leading to a long-term decline in memory performance. It can be imagined as the synapses bursting, in a sense. Everything that was previously in the synapses is released at this moment – including beta-synuclein. At this point, it becomes relevant for research because it enters the bloodstream. By examining the concentration of beta-synuclein in the blood, conclusions can be drawn about the progression of Alzheimer's disease, even in the early stages when the deterioration of the brain has not yet triggered any noticeable symptoms.
The more synapses are destroyed, the higher the beta-synuclein concentration
What role beta-synuclein plays in the brain itself is still unknown. The protein was first described in the 1990s. It is thought to be involved in synaptic function, but the exact mechanism behind this has not yet been researched. It is so informative as a biomarker—i.e., an indicator—because it only occurs in the brain. Diseases elsewhere in the body therefore have no direct influence on beta-synuclein levels. At the same time, however, it also rises whenever many synapses are destroyed, and this is not only the case in Alzheimer's patients, but also after a stroke, traumatic brain injury, or other neurodegenerative diseases. For this reason, beta-synuclein concentration is not suitable as a sole indicator of Alzheimer's disease; it must be incorporated into a comprehensive diagnostic approach. In addition, research has now identified other markers, such as phospho-tau, which change much earlier in Alzheimer's disease than beta-synuclein levels.
Beta-synuclein is therefore particularly relevant to the question of when degeneration begins in the course of the disease. While other indicators such as phospho-tau appear many years before the first recognizable symptoms of the disease, the beta-synuclein indicator is directly linked to the actual loss of nerve cells, i.e., irreversible damage to the brain.
A blood sample is sufficient
In order for new drugs such as lecanemab to be administered at exactly the right moment when they are most effective, it would be necessary to look inside the body, so to speak, in order to accurately map the course of the disease. Looking at beta-synuclein levels could make this possible. A groundbreaking study has shown the way to this goal. The special feature of this study was that, for the first time, blood samples could be used for this purpose. Previously, researchers had to rely on tests using cerebrospinal fluid, which is medically more complicated to obtain and often causes anxiety.
Further investigations and studies such as DELCODE and DIAN are currently underway at the DZNE, which aim, among other things, to determine how the concentration of beta-synuclein changes over the course of the disease. It has already been shown that the more severe the cognitive impairment, the higher the beta-synuclein content in the blood. It is also conceivable that beta-synuclein could provide clues as to how well a treatment is working: Does the concentration in the blood drop again when a drug stops or slows down the degeneration of nerve cells? Such findings could make a significant contribution to effective treatment in the future.