The platelet has been suggested to be a peripheral model of the central serotonergic neuron. This investigation was carried out in order to test the hypothesis that levels of serotonin (5-HT) in the platelet will be decreased in Alzheimer's disease (AD) since neurochemical studies suggest that levels of 5-HT are decreased in the brain of AD patients. We investigated platelet and plasma 5-HT in a group of AD patients (n = 22) as well as in age-matched normal control subjects (n = 20). The results show that the platelet level of 5-HT was significantly reduced in AD (65.7 +/- 28.41 ng/10(8) platelets in AD vs. 112.9 +/- 35.11 ng/10(8) platelets in controls; p = 0.0001). There was no effect on the levels of its metabolite 5-hydroxyindoleacetic acid. These findings suggest that the peripheral serotonergic system in AD is adversely affected.