- Cláudia Almeida and Mariana Barata uncover risk gene mechanism that deregulates brain activity
- Epilepsy drug shows potential to protect the brain
A team of researchers at NOVA Medical School has discovered a mechanism associated with Alzheimer’s disease that could potentially be treated with an anticonvulsant drug already available on the market. The research, led by Cláudia Almeida, shows how the loss of function of the BIN1 protein - strongly linked to the risk of developing Alzheimer’s disease - causes brain hyperactivity that triggers seizures similar to epilepsy, paving the way for new treatments. The study was published in the scientific journal Cell Reports.
“Our main finding was that BIN1 plays a crucial role in maintaining inhibitory synapses, countering previous discoveries. Inhibitory synapses act as the brain’s natural brakes. When BIN1 stops functioning, these brakes weaken, leading to neuronal hyperactivity - a mechanism associated with seizures and epilepsy. Interestingly, some Alzheimer’s patients develop epilepsy,” explain Cláudia Almeida and Mariana Barata, the study’s lead authors.
At this point, the anticonvulsant drug already used in epilepsy treatment comes into play. “This discovery opens new possibilities for early interventions to protect brain function and suggests that existing drugs, such as Levetiracetam, may help control the progression of Alzheimer’s disease long before symptoms appear,” the researchers argue, using an analogy to explain the process: “The brain is like a busy city where traffic lights control the flow of cars. Inhibitory synapses are the red lights that stop traffic to prevent chaos. BIN1 helps keep the traffic lights working. When BIN1 is lost, the signals fail - the traffic (neuronal activity) increases uncontrollably, causing accidents/seizures (hyperexcitability). Levetiracetam acts as an emergency traffic controller, helping to restore order.”
The study, carried out in collaboration with Edgar Gomes of the Gulbenkian Institute for Molecular Medicine, not only reinforces the role of the BIN1 protein in the origins of the disease but also raises new research questions: Is it possible to enhance the function of this protein? And could Levetiracetam or similar drugs truly delay Alzheimer’s progression in patients with high genetic risk?
Although further studies and clinical trials are needed, the discovery represents a promising step forward in the fight against a neurodegenerative disease estimated to affect 1 in 10 people over the age of 65 and around 50 million people worldwide.
Read the full study “Alzheimer's genetic risk factor Bin1 controls synapse vesicle exo-endocytosis in inhibitory synapses” at: https://pubmed.ncbi.nlm.nih.gov/40674214/