Topic: neuronal hyperactivity

The reduction of amyloid beta (Aβ) has been shown to be effective in treating Alzheimer’s Disease (AD), but an underlying assumption that neurons are the main source of pathogenic Aβ remains untested. Here we show that oligodendrocytes produce significant amounts of Aβ, which in turn promotes abnormal neuronal hyperactivity in AD. Initially, we assessed publicly available single cell RNA-sequencing and proteomics databases and showed that oligodendrocytes express all the components required to produce Aβ. By employing RNAscope in situ hybridisation we revealed that the brains of AD patients ha

To understand how amyloidosis in Alzheimer’s Disease changes circuit properties affecting memory encoding and recall, we examined the relationship between neuronal activity, nearness to amyloid plaques, and spatial memory readout from hippocampal CA1 place cells. We performed two-photon calcium imaging in head-fixed 5xFAD mice navigating an air-lifted circular track. Neuronal hyperactivity in CA1 during non-running periods was higher in 5xFAD mice compared to wildtype littermates in both young (2-3 months) and old (6.5-10 months) groups. Moreover, neurons close to amyloid plaques (<20µm in