J Physiol. 2026 Mar 10. doi: 10.1113/JP286196. Online ahead of print.
ABSTRACT
In early stages of Alzheimer's disease (AD), soluble amyloid-β (Aβ) is a key player disrupting neuronal activity and contributing to cognitive decline in advanced stages of the disease. Although the hippocampus has been a central focus in prior research because of its susceptibility to Aβ-induced alterations, a comprehensive understanding of the temporal progression of early AD pathology requires exploring interconnected brain regions. The posterior parietal cortex (PPC), collaborating closely with the hippocampus and involved in various memory processes, particularly spatial memory formation, holds particular significance. Investigating the function of the PPC is imperative because it may contribute to early AD characteristics and provide a more holistic perspective on disease progression. To address this gap, we examined the relationship between neural oscillations and memory processes in both the PPC and hippocampus, in a mouse model of early hippocampal amyloidosis generated by intracerebroventricular oligomeric Aβ (oAβ) injection. By performing in vivo oscillatory activity recordings from these regions in alert animals, together with spatial and habituation memory tests (Barnes maze and open field habituation), we found oAβ to induce significant alterations in PPC oscillatory activity. These changes emerged several days after hippocampal disturbances showed as aberrant synaptic plasticity and network activity. Additionally, significant alterations of stereotyped behaviours 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, investigating PPC oscillatory activity might be a valuable approach for early detection and intervention in AD. KEY POINTS: Posterior parietal cortex (PPC), in close collaboration with the hippocampus, has been implicated in various memory processes disrupted in early Alzheimer's disease models. A mouse model of early Alzheimer's-like hippocampal amyloidosis generated by intracerebroventricular oligomeric Aβ (oAβ1 42) injection was used to examine the relationship between neural oscillations and memory processes in both the PPC and hippocampus. oAβ induces alterations in spatial and habituation memory, associated with PPC aberrant oscillatory activity, several days after hippocampal synaptic plasticity and network activity disturbances were found. We provide an electrophysiological PPC-mediated substrate for persistent spatial memory deficits and the temporal progression pattern of the early oscillatory deleterious effects caused by Aβ.
PMID:41806092 | DOI:10.1113/JP286196