Neopterin and dementia in Down syndrome

Objectives: Down syndrome (DS) is associated with both Alzheimer’s dementia (AD) and altered immune responses and increased susceptibility to infectious diseases. Inflammation and immune system activation are considered to be involved in the pathogenesis of dementia. Plasma levels of C-reactive protein may reflect an acute phase reaction; plasma neopterin levels are considered to indicate cell mediated immune activation and inflammation. It is uncertain whether plasma neopterin levels are associated with the onset and progression of dementia. In the present study plasma neopterin levels were measured in a large group of DS patients with and without AD. Methods: A total of 506 patients with DS were included. Each patient had a complete physical and neurological assessment supplemented with interviews with care givers. All medical records were reviewed for relevant data. Examinations were repeated each year. The diagnosis AD was made according to the guidelines of the IASSID and a dementia questionnaire. Neopterin was measured blind to the dementia status. The median value was used to delineate high versus low concentrations. Results: The mean plasma concentration of neopterin was 25.18 nmol/l (range: 4.58-90.10 nmol/l) resulting in a median value of 22.61 nmol/l (cut off point). Patients aged 60 years or more had a significantly higher neopterin concentration. In the AD subgroup neopterin was significantly increased as compared to the non-AD subgroup. After correction for autoimmune disorders, these differences were more pronounced. Discussion: AD in DS is associated with higher neopterin levels and neopterin is an independent predictor of the development of dementia.