Functional aberration of cortical neuronal network induced by Aβ42 oligomer

Abstract

Alzheimers disease (AD) is a multifactorial disorder that affects cognitive functioning, behavior, and neuronal properties. The neuronal dysfunction is primarily responsible for cognitive decline in AD patients, with many causal factors including plaque accumulation of A{beta}42. Neural hyperactivity induced by A{beta}42 deposition cause abnormalities in neural networks, leading to alterations in synaptic activity and interneuron dysfunction. Even though neuroimaging techniques elucidated the underlying mechanism in the neural connectivity, precise understanding in cellular level is still elusive. Previously, a few multielectrode array studies examined the neuronal network modulation in vitro cultures revealing relevance of ion channels and the chemical modulators in the presence of A{beta}42. In this study, we investigated neuronal connectivity and dynamic changes with high density multielectrode array, particularly in relation to network-wide parameter changes over time. By comparing the neuronal network between normal and A{beta}42 treated neuronal cultures, it was possible to discover the direct pathological effect of the A{beta}42 oligomer altering the network characteristics. The application of graph theory and center of activity trajectory analysis assessed the consolidation and disassociation of neural networks under A{beta}42 oligomer exposure over time. This result can enhance our understanding of how neural networks are affected during AD progression.