The Study of Neuronal Hyperactivity in the Early Stage of Alzheimer’s Disease

Alzheimer’s disease (AD) is a neurodegenerative disease, characterized by memory loss and cognitive impairment. The pathology of AD includes the accumulation of beta‐amyloid (Aβ) in the extracellular space and hyper‐phosphorylation of tau in neurons. Aβ pathology has been shown to begin approximately 20 years before tau pathology and mild cognitive impairment develop in AD patients. Aβ deposits cause alterations in brain function, leading to the loss of neurons in the cerebral cortex and hippocampus in the later stages of AD. However, the cellular mechanisms by which Aβ induces AD pathology remain largely elusive. Traditionally, lower neuronal activity has been thought to contribute to the synaptic failure and cognitive impairments observed in AD. However, recent studies suggest that Aβ triggers neuronal hyperactivity during the early stages of AD. Consistent with this observation, epileptic seizures have been detected in both mouse models of AD and human patients with Alzheimer’s. Uncontrolled or severe seizures can lead to further brain damage and exacerbate the cognitive decline seen in AD. Thus, neuronal hyperactivity could be one of the contributing factors to the neuronal loss induced by Aβ. However, it is unclear how Aβ can induce neuronal hyperactivity and seizures.