Neuroscience Letters 458 (2009) 60–64 Contents lists available at ScienceDirect Neuroscience Letters journal homepage: www.elsevier.com/locate/neulet Neopterin and the risk of dementia in persons with Down syndrome Antonia M.W. Coppus a,b,∗ , Durk Fekkes c,d , Willem M.A. Verhoeven d,e , Heleen M. Evenhuis f , Cornelia M. van Duijn b a Dichterbij, Centre for the Intellectually Disabled, Gennep, The Netherlands b Department of Epidemiology and Biostatistics, Erasmus University Medical Centre, Rotterdam, The Netherlands c Department of Neuroscience, Erasmus University Medical Centre, Rotterdam, The Netherlands d Department of Psychiatry, Erasmus University Medical Centre, Rotterdam, The Netherlands e Vincent van Gogh Institute for Psychiatry, Venray, The Netherlands f Department of General Practice, Intellectual Disability Medicine, Erasmus University Medical Centre, Rotterdam, The Netherlands article info Article history: Received 11 January 2009 Received in revised form 29 March 2009 Accepted 9 April 2009 Keywords: Neopterin Down syndrome Alzheimer’s disease Autoimmune disease abstract Persons with Down syndrome show an altered immune response and an increased susceptibility to Alzheimer’s disease. In a prospective study, we examined whether the plasma neopterin level, a marker for cell-mediated immune activation and inflammation, is associated with an increased risk of dementia in persons with Down syndrome. Plasma concentrations of neopterin were determined in a population- based study of 394 persons with Down syndrome, who were screened annually for dementia. We used Cox proportional hazards model to determine risk of dementia. Demented persons with Down syndrome have a significantly (p = 0.05) higher plasma neopterin concentration than the non-demented. In the non- demented without autoimmune disorders, in those with a plasma level of neopterin above median, the risk to develop dementia increased to 1.83 (95% confidence interval: 1.04–3.20). High plasma neopterin level is an independent determinant of the risk of dementia in persons with Down syndrome. © 2009 Elsevier Ireland Ltd. All rights reserved. Down syndrome (DS) is a common genetic disorder affecting about 1 in 750 live births in the general population. It is caused by a complete, or occasionally partial, triplication of chromosome 21, which explains the increased risk of Alzheimer’s disease (AD) and dementia. Despite the relatively uniform cause of dementia in per- sons with Down syndrome, patients with dementia show a large spread in the onset age of dementia. This can vary from age 35 to 70 years which suggests other risk factors may modify the onset of disease [2]. Persons with DS also show an altered immune response and an increased susceptibility to infectious diseases and immune mediated and aging-associated diseases [9]. Among the various pathophysiological mechanisms involved in dementia in the general population, inflammation and immune system activation are considered to play an important role in the development and progression of dementia [16]. Increased concen- trations of immune activation markers, including C-reactive protein (CRP), tumor necrosis factor- and neopterin, were reported in the brain but also in the blood of patients with AD and other neurode- generative disorders [12,19]. While plasma levels of CRP may reflect ∗ Corresponding author at: Department of Epidemiology and Biostatistics, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. Tel.: +31 107043394; fax: +31 107044657. E-mail address: a.coppus@erasmusmc.nl (A.M.W. Coppus). an acute phase reaction, plasma neopterin levels are more likely to reflect cell-mediated immune activation and inflammation [19]. In a previous study we found, in healthy persons with DS, aged 45 years and older, an increased plasma concentration of neopterin [3]. It is unknown whether plasma neopterin levels are associated with AD in persons with DS or with the onset of disease. The aim of this study is to investigate whether plasma neopterin levels in persons with DS are associated with the risk of dementia. We conducted a study of 506 persons with DS, aged 45 years and older, who were enrolled from 1 December 1999 until 1 December 2003 in a community-based study on DS and ageing in the Netherlands. Informed consent procedures and recruit- ing of subjects have been described in detail elsewhere [2]. At the time of study entry, each person received a complete assessment including interviews with relatives, carers and the gen- eral practitioner. All medical records were reviewed to disclose past or present medical disorders, such as epilepsy and depres- sion, and the possible use of drugs. The same questionnaires and interviews were used annually from 1999 to 2007. All per- sons underwent a general physical and neurological examination. Venous blood samples were taken fasting in the morning. From the 506 participants included, plasma concentration of neopterin was measured in 394 (77.9%) persons who consented to give (suf- ficient) blood. All participants were assessed once yearly up to the reference date of 1 January 2007 or to the date of death. 0304-3940/$ – see front matter © 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.neulet.2009.04.020