2026 Volume 43 Issue 2 Pages 114-118
Alzheimer disease (AD) is a progressive neurodegenerative disorder characterized by pathological deposition of amyloid β (Aβ) and tau protein aggregation followed by neuronal loss. Emerging evidence suggests that abnormal brain network activity precedes overt neurodegeneration and accelerates disease progression. Disruption of the excitation/inhibition (E/I) balance, particularly due to dysfunction of inhibitory interneurons such as parvalbumin–positive interneurons, may contribute to epileptiform activity and cognitive decline. Neuroinflammation further exacerbates this imbalance through astrocytic and microglial mechanisms, including altered GABA signaling and synaptic pruning. These findings highlight circuit–level dysfunction of GABAergic system as an early biomarker and therapeutic target. Recent approaches, such as antiepileptic drugs, PV neuron modulation, and non–invasive stimulation, offer promise in restoring network stability and mitigating pathology. Understanding the interplay between neuronal and glial components in E/I regulation will be critical for developing innovative strategies to attenuate AD progression.
