Increased amyloid β protein levels in children and adolescents with Down syndrome

Background: Persons with Down syndrome (DS) (40 years and older) have neuropathological changes characteristic of Alzheimer disease (AD). Soluble forms of amyloid beta (A beta) peptide generated from amyloid precursor protein (APP) end at C-terminal residues 40 and 42. The presence of the apolipoprotein E (ApoE) epsilon 4 allele is a significant risk factor for the development of sporadic AD. Although preliminary studies have shown an association of plasma A beta S2 and A beta po epsilon 4 allele in older persons with DS who have dementia, the relationship between plasma A 40 and A 42 levels and ApoE phenotypes in children with DS has not been examined. Inflammation might play a role in the growth of DS brains. Neopterin is an immune activation marker for the cell-mediated immune response. Objective: To examine the levels of plasma A beta 40, A beta 42, and neopterin in children or adolescents with DS or controls. Materials and methods: Blood was collected from DS (N=35; 7 +/- 3.8 years old) and their siblings (N=34; 10 +/- 4.5). Plasma A beta 40 and A beta 42, and neopterin levels were quantitated by sandwich ELISA. Results: A beta 40 and A beta 42 levels were higher in DS than controls. The ratio of A beta 2/A beta 40 was lower in DS than in controls. There were significant negative correlations between age and A beta 40 in DS and controls, and between age and A beta 42 levels in DS but not in controls. There was no association of A beta 40 or A beta 42 levels with Apo E in either group. Neopterin levels were higher in DS than controls, and the levels were not correlated with A beta 40 and A beta 42 levels in DS or controls. Conclusions: The over expression of APP gene in DS leads to increases in plasma A beta 40 and A beta 42 levels before plaque formation in DS brain. Higher neopterin concentrations in DS reflect inflammatory cell activation. Further studies are needed to determine whether DS children with lower plasma A beta 42/A beta 40 ratios are at increased risk of developing AD during aging than those with higher ratios. (c) 2007 Elsevier B.V. All rights reserved.