A disorder of cortical GABAergic innervation in Alzheimer's disease

Synaptosomal gamma-aminobutyric acid (GABA) uptake has been used as a biochemical marker for GABAergic terminals in controls and Alzheimer disease brains. Use of this marker suggests a large (ca. 70%) loss of cortical and hippocampal GABA terminals in Alzheimer brain. To explain this observation we suggest that neuron loss in this disorder occurs via a process of cortical retrograde degeneration. This scheme reconciles our findings with previous neurochemical measurements on Alzheimer disease brains and also better reconciles the biochemistry with the histology of the disorder.