Serotonin (5-HT) in brains of adult patients with Down syndrome.

Down syndrome (DS) is a genetic disease with developmental brain abnormalities resulting in early mental retardation and precocious, age dependent Alzheimer-type neurodegeneration. Furthermore, non-cognitive symptoms may be a cardinal feature of functional decline in adults with DS. As the serotonergic system plays a well known role in integrating emotion, cognition and motor function, serotonin (5-HT) and its main metabolite, 5-hydroxyindol-3-acetic acid (5-HIAA) were investigated in post-mortem tissue samples from temporal cortex, thalamus, caudate nucleus, occipital cortex and cerebellum of adult patients with DS, Alzheimer's disease (AD) and controls by use of high performance liquid chromatography (HPLC). In DS, 5-HT was found to be age-dependent significantly decreased in caudate nucleus by 60% (DS: mean +/- SD 58.6 +/- 28.2 vs. Co: 151.7 +/- 58.4 pmol/g wet tissue weight) and in temporal cortex by about 40% (196.8 +/- 108.5 vs. 352.5 +/- 183.0 pmol/g), insignificantly reduced in the thalamus, comparable to controls in cerebellum, whereas occipital cortex showed increased levels (204.5 +/- 138.0 vs. 82.1 +/- 39.1 pmol/g). In all regions of DS samples, alterations of 5-HT were paralleled by levels of 5-HIAA, reaching significance compared to controls in thalamus and caudate nucleus. In AD, 5-HT was insignificantly reduced in temporal cortex and thalamus, unchanged in cerebellum, but significantly elevated in caudate nucleus (414.3 +/- 273.7 vs. 151.7 +/- 58.4 pmol/g) and occipital cortex (146.5 +/- 76.1 vs. 82.1 +/- 39.1 pmol/g). The results of this study confirm and extend putatively specific 5-HT dysfunction in basal ganglia (caudate nucleus) of adult DS, which is not present in AD. These findings may be relevant to the pathogenesis and treatment of cognitive and non-cognitive (behavioral) features in DS.