Amino Acids (2010) 38:923–928 DOI 10.1007/s00726-009-0300-5 O R I G I N A L A R T I C L E Plasma levels of nitric oxide related amino acids in demented subjects with Down syndrome are related to neopterin concentrations A. M. W. Coppus Æ D. Fekkes Æ W. M. A. Verhoeven Æ S. Tuinier Æ C. M. van Duijn Received: 19 April 2009 / Accepted: 21 April 2009 / Published online: 20 May 2009 The Author(s) 2009. This article is published with open access at Springerlink.com Abstract Subjects with Down syndrome (DS) have abnormalities in virtually all aspects of the immune system and almost all will be affected with Alzheimer’s disease (AD). It is thought that nitric oxide (NO) is involved in the pathophysiology of AD. In the present study, including a total of 401 elderly DS subjects, the spectrum of plasma amino acids and neopterin was investigated and related to development of AD. Concentrations of nearly all amino acids in DS subjects differed signiﬁcantly from those of healthy controls. Neopterin was increased in DS subjects, especially in dementia. The production of NO as reﬂected by an increased citrulline/arginine ratio (Cit/Arg ratio) was enhanced during development of clinical dementia. Neop- terin concentrations correlated to the Cit/Arg ratio only in the group of prevalent demented subjects (q = 0.48, A. M. W. Coppus (&) Centre for the Intellectually Disabled, Dichterbij, Gennep, The Netherlands e-mail: a.coppus@erasmusmc.nl A. M. W. Coppus C. M. van Duijn Department of Epidemiology, Erasmus University Medical Centre, Rotterdam, The Netherlands D. Fekkes Department of Neuroscience, Erasmus University Medical Centre, Rotterdam, The Netherlands W. M. A. Verhoeven S. Tuinier Vincent van Gogh Institute for Psychiatry, Venray, The Netherlands D. Fekkes W. M. A. Verhoeven Department of Psychiatry, Erasmus University Medical Centre, Rotterdam, The Netherlands P = 0.006). The results of this study are suggestive for an increase in oxidative processes in DS subjects with AD. Keywords Nitric oxide Amino acids Down syndrome Neopterin Branched chain amino acids Introduction Down syndrome (DS) is a common genetic disorder with a prevalence of 1:750 and is caused by a complete or occa- sionally partial triplication of chromosome 21. Its preva- lence is highly dependent on maternal age at gestation. It is well known that individuals with DS have an increased rate of congenital and acquired medical complications includ- ing among others thyroid gland dysfunction. Abnormalities have been reported in virtually all aspects of the immune system resulting in a greater susceptibility to infectious disease. Finally, they have a higher risk for hematological malignancies, particularly leukemia’s, and virtually all show the neuropathological changes of Alzheimer’s dis- ease (AD) by the age of 35–40 years. This may be due to an increased production of the amyloid precursor protein (Cheon et al. 2008; Lockstone et al. 2007). Onset of clin- ical dementia is in general in the ﬁrst half of the sixth decade. With respect to psychopathology, depression is frequently diagnosed and shows an age related increase (Hunter 2005). A growing body of evidence indicates that there is an increased oxidative stress in AD brains and it is hypothe- sized that nitric oxide (NO) can be related to many of the pathophysiological mechanisms of AD (Akomolafe et al. 2006; Moreira et al. 2008). The presence of any stimulant that leads to an overproduction of NO will probably cause neuronal damage (Akyol et al. 2004). The biologically 123