Alzheimer's & dementia : the journal of the Alzheimer's Association
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To propose a new hypothesis that GABAergic dysfunction in excitatory and inhibitory (E/I) imbalance drives the pathogenesis of Alzheimer's disease (AD). ⋯ Dysfunction of the GABAergic system is induced by multiple critical signaling pathways, which include the existing major theories of AD pathogenesis, such as the Aβ and neuroinflammation hypotheses. In a new perspective, this GABAergic hypothesis accounts for the E/I imbalance and related excitotoxicity, which contribute to cognitive decline and AD pathogenesis. Therefore, the GABAergic system could be a key target to restore, at least partially, the E/I balance and cognitive function in AD patients.