Involvement of the GABAergic system in depressive symptoms of Alzheimer's disease

Cognitive and neuropsychiatric (BPSD) symptoms seen in Alzheimer's disease (AD) probably result from differential neurotransmitter alterations. The involvement of the glutamatergic and GABAergic system in cognitive and behavioral and psychological symptoms of dementia (BPSD) has been studied in post-mortem frontal and temporal cortex from AD patients who had been prospectively assessed with the Mini-Mental State Examination (MMSE) for cognitive impairment and with the Present Behavioral Examination (PBE) for BPSD. In addition to cholinergic deficits, significant decreases in γ-amino butyric acid (GABA) content, with no changes in glutamate content, were found in frontal and temporal cortex. Both GABA levels and the glutamate/GABA ratio showed significant correlations with depression in AD. In the temporal cortex, higher densities of GABAA/benzodiazepine receptors also correlated with more severe depression. It can be suggested that in a situation of cholinergic deficit, such as AD, an imbalance between the excitatory glutamatergic tone and inhibitory GABAergic tone may be responsible for non-cognitive behavioral disturbances.