Disturbance of the 5-hydroxytryptamine metabolism in brains from patients with Alzheimer's dementia

Abstract

The 5-hydroxytryptamine (5-HT) system in the human brain is sensitive to aging. In dementia of the Alzheimer type (AD/SDAT), there are significantly reduced concentrations of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA). 5-HT-sensitive imipramine binding is reduced by almost 50%, indicating a loss of presynaptic 5-HT terminals. There also seems to be reduced tryptophan hydroxylase activity in some brain areas. In cerebrospinal fluid (CSF) from AD/SDAT patients, the concentration of 5-HIAA is reduced, and the accumulation of 5-HIAA after probenecid loading is diminished. Biochemical findings together with structural findings in the raphe nuclei indicate that the disturbance of the 5-HT system is of the same magnitude as the disturbance of the cholinergic system. Reduced activity in the 5-HT system may be of importance for activity in the hypothalamus. There is an increased concentration of arginine vasopressin, which may explain the increased activity in the hypothalamic-pituitary-adrenal axis seen in patients with AD/SDAT. This activity is reduced when a selective 5-HT reuptake blocker is given. Pharmacological treatment with 5-HT reuptake blockers improves emotional disturbances, confusion, anxiety and depressed mood in patients with AD/SDAT.