Gamma-aminobutyric acid concentration in brain tissue at two stages of Alzheimer's disease.

The concentration of the inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), was measured in the cerebral cortex obtained at diagnostic craniotomy from 10 patients with Alzheimer's disease of 3 yrs mean duration and 6 patients with other causes of dementia, and from 31 subjects undergoing other neurosurgical procedures (for which removal of apparently normal tissue was necessary). GABA content of 5 areas of the cerebral cortex and the cerebellar cortex was measured postmortem in the brains of 23 Alzheimer and 19 control subjects and 5 patients with other causes of dementia. Fourteen of these specimens, including 7 from patients with Alzheimer's disease of 8 yrs mean duration, were obtained within 3 h of death. These were processed in a similar manner to the neurosurgical specimens and are regarded also as fresh tissue samples. The remaining 33 specimens are regarded as conventional postmortem samples as the mean interval of death to autopsy was 21 h. GABA concentration in conventional autopsy specimens from Alzheimer subjects was not reduced as compared with controls in either cingulate or cerebellar cortex. In the inferior parietal cortex, agonal status confounded this comparison. The concentration was reduced in superior parietal, frontal and temporal cortex but there is a possibility that agonal state also confounded these comparisons. There was no deficit in GABA concentration in fresh cortical tissue from Alzheimer patients except for the temporal lobe from autopsy specimens. The content of somatostatin-like immunoreactivity was, like GABA, found to be comparable to control in some groups of Alzheimer specimens. It is argued that the deficits in autopsy samples and lack of change in surgical specimens is likely to be due to the duration of illness at the time of sampling. Losses of choline acetyltransferase activity were observed in all groups of Alzheimer specimens in all areas of brain studied. The data are consistent with other results which suggest that cholinergic under-activity is most closely related to the clinical course of Alzheimer's disease.