Posterior parietal cortex oscillatory activity shapes persistent spatial memory impairments induced by soluble amyloid-β oligomers

In the initial stages of Alzheimer's disease (AD), the presence of soluble amyloid-β (Aβ) peptides is known to perturb neuronal activity, leading to cognitive decline in advanced stages of the disease. While the hippocampus remains a focal point due to its vulnerability to Aβ, a comprehensive understanding of early-stage AD pathology requires the examination of interconnected neural regions, such as the posterior parietal cortex (PPC). The PPC, intricately linked with the hippocampus and essential to memory functions, particularly spatial memory, is vital for decoding early symptoms and the progression of AD.Our study deepens in the interaction between neural oscillations and memory processes in the PPC and hippocampus in a mouse model of early hippocampal amyloidosis, generated by intracerebroventricular oligomeric Aβ1-42 (oAβ1-42) injections. Carrying out in vivo electrophysiology to record oscillatory activity in these regions alongside spatial and habituation memory evaluations (utilizing the Barnes maze and open field habituation tests), we found oAβ1-42 to induce significant alterations in PPC oscillatory activity emerging several days after hippocampal disturbances showed as aberrant synaptic plasticity and network activity. Additionally, significant alterations of stereotyped behaviors were not found.Our results provide an electrophysiological substrate for persistent spatial memory deficits and the temporal progression pattern of the early deleterious effects caused by Aβ. Furthermore, they support the potential use of PPC oscillatory activity as a valuable tool for early detection and intervention in AD. Acknowledgements: MCIN, PID2020-115823-GB100 / JCCM, SBPLY/21/180501/000150 and ERDF. AC, NextGenerationEU/PRTR postdoctoral fellowship.