Increased Amyloid β Protein Levels in Children with Down Syndrome (129.47)

Abstract

Abstract Objective: To quantitate plasma amyloid β protein (Aβ)40, Aβ42, and neopterin levels in Down Syndrome (DS) children and controls. Background: DS persons (>40 years) have neuropathological changes characteristic of Alzheimer disease (AD). Soluble forms of Aβ generated from amyloid precursor protein (APP) end at C-terminal residues 40 and 42. Neopterin is an immune activation marker for the cell-mediated immune response. Design/Methods: Blood was collected from DS (N = 35; 7 ± 3.8 years old) and their siblings (N = 34; 10 ± 4.5). Plasma Aβ40, Aβ42, and neopterin levels were quantitated by ELISA. Results: Aβ40 (Mean ± SD; 277 ± 70 pg/ml) and Aβ42 (31 ± 8 pg/ml) levels were higher in DS children than controls (Aβ40 155 ± 35 pg/ml, Aβ42 22 ± 5 pg/ml) (p<.0001). There were significant negative correlations between age and Aβ40 in DS (r=.47, p<.004) or controls (r=.38, p<.026) and Aβ42 levels in DS (r=.61, p<.001) but not in controls. Neopterin levels were higher in DS (3.01 ± 1.37 ng/ml) than controls (1.57 ± 0.65 ng/ml) (p<.0001). There was no correlation between neopterin levels and age, and Aβ40 or Aβ42 levels in DS or controls. Conclusion: The overexpression of APP gene in DS leads to increases in plasma Aβ40 and Aβ42 levels before plaque formation in DS brain. A lack of correlation between neopterin and Aβ levels suggests that higher neopterin concentrations in DS reflect inflammatory cell activation rather than AD neuropathology.