The role of the GABAergic system in Alzheimer’s disease: Mechanisms linking anxiety and therapeutic implications

ABSTRACT Alzheimer’s disease (AD) is a progressive, neurodegenerative disorder characterized by cognitive decline and neuropsychiatric symptoms such as anxiety and depression. Approximately 75% of AD patients suffer from anxiety. Aging is the foremost detrimental factor for AD and anxiety; thus, anxiety disorder brings obstacles to clinical diagnosis and management of AD patients. Although a few FDA-approved drugs available for AD in recent years, these drugs only provide symptomatic relief, cannot slow down or reverse AD progression in the advanced stages, and anxiety associated with AD. There is mounting evidence that gamma-aminobutyric acidergic (GABAergic) system plays a role in the pathogenesis of AD and anxiety. However, how GABAergic system dysfunction results in AD-related anxiety is unknown. In the present review, we aimed to summarize the mechanisms of GABAergic system in AD-related anxiety and provide with theory help for AD-related anxiety therapeutics. We propose a concept of an interactive mechanism framework of GABAergic system in anxiety and AD progression. Regulation of GABAergic system associated with AD can provide a potential intervention for this devastating disease and the comorbidity of anxiety.