Milwaukee – Cognitive decline caused by Alzheimer’s disease does not depend solely on the accumulation of the disease’s characteristic pathological proteins but is closely linked to the loss of functionality in synaptic connections – a process that begins long before the first clinical symptoms appear. A new study, coordinated by Ramona Stringhi and Silvia Pelucchi, respectively a research fellow and a pharmacology researcher at the Department of Pharmacological and Biomolecular Sciences “Rodolfo Paoletti” at the University of Milan, examined the early stages of the disease with the aim of preventing synaptic damage and strengthening the ability of neural networks to remain functional over time. At the center of the research, published in Molecular Therapy, is a protein called Cyclase-Associated Protein 2 (CAP2), involved in regulating the actin cytoskeleton – a network of protein filaments in the cell cytoplasm that plays a crucial role, particularly in maintaining the shape and stability of dendritic spines, small protrusions essential for synaptic transmission and brain plasticity. When the cytoskeleton is altered, the structure and function of synapses can also be compromised. Previous studies have shown that, in Alzheimer’s disease, CAP2 levels are reduced in the hippocampus, a brain region essential for memory. This suggests that the decrease in the protein may contribute to early alterations in neuronal connections. Based on these observations, researchers hypothesized that increasing CAP2 levels could help protect synapses. “The study suggests,” said Elena Marcello of the University of Milan, corresponding author of the research, “that early intervention to strengthen the mechanisms that keep neuronal connections stable could help slow or delay cognitive decline. Rather than repairing existing damage, this approach aims to prevent the loss of synaptic function and preserve neural networks over time. As this is a preclinical study, further research will be needed to determine whether this strategy can be developed into a potential therapeutic intervention in humans.” (9colonne)