A post-mortem study of noradrenergic, serotonergic and GABAergic neurons in Alzheimer's disease

Involvement of noradrenergic, serotonergic and GABAergic neurons in Alzheimer's disease/senile dementia of Alzheimer type (AD/SDAT) was studied in 20 histologically confirmed AD/SDAT cases by comparing these with 14 control patients. Concentrations of noradrenaline (NA) were decreased significantly in the frontal cortex, temporal cortex, hippocampus and putamen in AD/SDAT. Serotonin (5-HT) levels were significantly lowered in the hippocampal cortex, hippocampus, caudate nucleus and putamen and the concentrations of 5-HIAA, a metabolite of 5-HT, were reduced in 3 cortical areas, thalamus and putamen in patients with AD/SDAT. Furthermore, 5-HIAA/5-HT ratios were in general slightly lower in AD/SDAT reaching significance in the temporal and hippocampal cortex. Glutamic acid decarboxylase (GAD) enzyme activity was not changed significantly in AD/SDAT although patients without evidence of premortem hypoxia and hypovolemia showed a consistent trend for increased GAD activity in the thalamus, striatum and substantia nigra. These findings further confirm the involvement of NA and 5-HT neuronal systems in AD/SDAT. The damage of 5-HT neurons seemed to be more generalized and more severe than that of NA neurons. The possible clinical relevance of these findings is briefly discussed and the need for critical evaluations of the behavioral effects related to these abnormalities described in patients with AD/SDAT is emphasized.