The ReTune-AD project (Synchrony Restoration as a Precision Therapy for Alzheimer’s Circuits) will study alterations in neural activity coordination during the early stages of Alzheimer's. It will particularly focus on gamma oscillations, crucial brain electrical rhythms for interregional communication and memory.
The research team will analyze which neurons and neural networks lose this synchronization first and the underlying mechanisms. They will employ advanced brain recording and stimulation techniques to assess the possibility of normalizing affected circuit activity.
“"We could say it's about learning to 'retune' circuits whose activity has become uncoordinated. But, to do it rationally, we first need to know which neuronal populations are failing, what trace that failure leaves in brain activity, and what type of stimulation can correct it."
The ultimate goal is the restoration of coordination in affected brain circuits. To achieve this, transcranial alternating current stimulation (tACS), a non-invasive technique, will be used to modulate brain activity and study if it can improve memory function in animal models.
A key part of the project will connect findings from animal models with signals measurable in humans. "If we can identify common biomarkers, we can use that knowledge to design more rational and personalized stimulation strategies in the future," notes Márquez-Ruiz.
ReTune-AD proposes an innovative approach that restores coordinated brain circuit activity, rather than focusing solely on neuronal deterioration. The results could be relevant for other neurodegenerative diseases.
The Translational Laboratory of Brain Stimulation at UPO, led by Javier Márquez-Ruiz, will contribute its expertise in brain stimulation mechanisms. Its work will integrate with research from the Hospital del Mar Research Institute to analyze neural network synchronization in the early stages of Alzheimer's.
Javier Márquez-Ruiz highlights the challenge of applying uniform protocols to an extraordinarily heterogeneous disease, emphasizing the goal of advancing towards 'precision neuromodulation' tailored to each specific brain circuit alteration.
The selection of ReTune-AD for the Pasqual Maragall Researchers Programme 2025 recognizes the innovative nature of this research, which seeks new avenues of knowledge on Alzheimer's and other age-related neurodegenerative diseases.
