Alzheimer's disease on CHIP
Aβ-induced neuronal dysfunctions and rescue studies by using 3Brain's CMOS-MEAs
Neurotoxicity and the accumulation of extracellular amyloid-beta1–42 (Aβ) peptides are associated with the development of Alzheimer’s disease (AD) and correlate with neuronal activity and network dysfunctions, ultimately leading to cellular death. However, research on neurodegenerative diseases is hampered by the paucity of reliable readouts and experimental models to study such functional decline from an early onset and to test rescue strategies within networks at cellular resolution. To overcome this important obstacle, in Amin et al., authors used 3Brain's CMOS-chips with 4096-electrodes to model AD on rat hippocampal cell culture. This model allows to monitor network activity changes at the cellular level and to uniquely uncover the early activity-dependent deterioration induced by Aβ-neurotoxicity. They demonstrated the potential of this in vitro model to test a plausible hypothesis underlying the Aβ-neurotoxicity and to assay potential therapeutic approaches. Specifically, by quantifying N-methyl D-aspartate (NMDA) concentration-dependent effects in comparison with low-concentration allogenic-Aβ, they demonstrated the role of extrasynaptic-NMDA receptors activation that may contribute to Aβ-neurotoxicity. Finally,they showed the potential rescue of neural stem cells (NSCs) and of two pharmacotherapies, memantine and saffron to reverse Aβ-neurotoxicity and rescuing network-wide firing.