**2.4 Gamma-Aminobutyric Acid receptor**

Gamma-Aminobutyric Acid receptor (GABAR) inhibition is also related to a better prognosis in AD. Gamma-Aminobutyric Acid receptor regulates learning, memory, and cognition, inhibits Adenylyl Cyclase and the cAMP cascade, as well as controls GABA and glutamate release. CGP35348 is a GABA receptor antagonist, and the CGP35348 hippocampal concentration is a crucial point for improving memory by reducing APP toxicity. Several neurological and psychiatric disorders occur with neuronal hyperexcitability in specific regions of the brain or spinal cord, partly due to some loss and/or dysfunction of GABAergic inhibitory interneurons [10]. Strategies which improve inhibitory neurotransmission in the affected brain regions may decrease deficits associated with these disorders. This perception has prompted an interest in testing the efficacy of GABAergic interneuron grafting in the brain or spinal cord regions which exhibit hyperexcitability, GABAergic interneurons scarcity, or impaired inhibitory neurotransmission, using preclinical models of neurological and psychiatric disorders [10]. Defective GABAergic neuronal functions can lead to cortical network hyperactivity and aberrant neuronal oscillations and thereby generate a detrimental change in memory processes [11]. In this context, GABAergic cell therapy may decrease neurological deficits in AD preclinical models [10]. Alzheimer patients have low GABA levels in the brain and spinal cerebrospinal fluid (SCF), and these changes are more severe in ApoE4 allele carriers. ApoE4 is associated with increased brain activity at rest and memory tasks, possibly reflecting impaired GABAergic inhibitory control. In addition, GABA levels in human SCF change with aging, constituting the strongest AD risk factor. Therefore, ApoE4 may at least partially contribute to the AD pathogenesis, causing age-dependent impairment in GABAergic interneurons [12].
