TY - JOUR
T1 - Increased amyloid β protein levels in children and adolescents with Down syndrome
AU - Mehta, Pankaj D.
AU - Capone, George
AU - Jewell, Amy
AU - Freedland, Robert L.
N1 - Funding Information:
This work was supported in part by a grant from the NIH (AG11290) and by NY State, Office of the Mental Retardation and Developmental Disabilities. The authors thank M. Barshatzky, S.P. Mehta and B.A. Patrick for their technical assistance and B. Patel and N. Schupf for statistical analysis. We extend our thanks to the many children and families who participated in this study; and to those individuals providing financial support for Down Syndrome Research at the Kennedy Krieger Institute.
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2007/3/15
Y1 - 2007/3/15
N2 - Background: Persons with Down syndrome (DS) (40 years and older) have neuropathological changes characteristic of Alzheimer disease (AD). Soluble forms of amyloid β (Aβ) peptide generated from amyloid precursor protein (APP) end at C-terminal residues 40 and 42. The presence of the apolipoprotein E (ApoE) ε4 allele is a significant risk factor for the development of sporadic AD. Although preliminary studies have shown an association of plasma Aβ42 and ApoE ε4 allele in older persons with DS who have dementia, the relationship between plasma Aβ40 and Aβ42 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 Aβ40, Aβ42, 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 Aβ40 and Aβ42, and neopterin levels were quantitated by sandwich ELISA. Results: Aβ40 and Aβ42 levels were higher in DS than controls. The ratio of Aβ42/Aβ40 was lower in DS than in controls. There were significant negative correlations between age and Aβ40 in DS and controls, and between age and Aβ42 levels in DS but not in controls. There was no association of Aβ40 or Aβ42 levels with Apo E in either group. Neopterin levels were higher in DS than controls, and the levels were not correlated with Aβ40 and Aβ42 levels in DS or controls. Conclusions: The over expression of APP gene in DS leads to increases in plasma Aβ40 and Aβ42 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 Aβ42/Aβ40 ratios are at increased risk of developing AD during aging than those with higher ratios.
AB - Background: Persons with Down syndrome (DS) (40 years and older) have neuropathological changes characteristic of Alzheimer disease (AD). Soluble forms of amyloid β (Aβ) peptide generated from amyloid precursor protein (APP) end at C-terminal residues 40 and 42. The presence of the apolipoprotein E (ApoE) ε4 allele is a significant risk factor for the development of sporadic AD. Although preliminary studies have shown an association of plasma Aβ42 and ApoE ε4 allele in older persons with DS who have dementia, the relationship between plasma Aβ40 and Aβ42 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 Aβ40, Aβ42, 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 Aβ40 and Aβ42, and neopterin levels were quantitated by sandwich ELISA. Results: Aβ40 and Aβ42 levels were higher in DS than controls. The ratio of Aβ42/Aβ40 was lower in DS than in controls. There were significant negative correlations between age and Aβ40 in DS and controls, and between age and Aβ42 levels in DS but not in controls. There was no association of Aβ40 or Aβ42 levels with Apo E in either group. Neopterin levels were higher in DS than controls, and the levels were not correlated with Aβ40 and Aβ42 levels in DS or controls. Conclusions: The over expression of APP gene in DS leads to increases in plasma Aβ40 and Aβ42 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 Aβ42/Aβ40 ratios are at increased risk of developing AD during aging than those with higher ratios.
KW - Amyloid β protein
KW - Down syndrome
KW - Enzyme linked immunosorbent assay
KW - Inflammation
KW - Neopterin
KW - Plasma
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U2 - 10.1016/j.jns.2006.12.010
DO - 10.1016/j.jns.2006.12.010
M3 - Article
C2 - 17275850
AN - SCOPUS:33847304909
SN - 0022-510X
VL - 254
SP - 22
EP - 27
JO - Journal of the Neurological Sciences
JF - Journal of the Neurological Sciences
IS - 1-2
ER -