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Increased amyloid beta protein levels in children and adolescents with Down syndrome.
J Neurol Sci. 2007 Mar 15; 254(1-2):22-7.JN

Abstract

BACKGROUND

Persons with Down syndrome (DS) (40 years and older) have neuropathological changes characteristic of Alzheimer disease (AD). Soluble forms of amyloid beta (Abeta) peptide generated from amyloid precursor protein (APP) end at C-terminal residues 40 and 42. The presence of the apolipoprotein E (ApoE) epsilon4 allele is a significant risk factor for the development of sporadic AD. Although preliminary studies have shown an association of plasma Abeta42 and ApoE epsilon4 allele in older persons with DS who have dementia, the relationship between plasma Abeta40 and Abeta42 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 Abeta40, Abeta42, 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 Abeta40 and Abeta42, and neopterin levels were quantitated by sandwich ELISA.

RESULTS

Abeta40 and Abeta42 levels were higher in DS than controls. The ratio of Abeta42/Abeta40 was lower in DS than in controls. There were significant negative correlations between age and Abeta40 in DS and controls, and between age and Abeta42 levels in DS but not in controls. There was no association of Abeta40 or Abeta42 levels with Apo E in either group. Neopterin levels were higher in DS than controls, and the levels were not correlated with Abeta40 and Abeta42 levels in DS or controls.

CONCLUSIONS

The over expression of APP gene in DS leads to increases in plasma Abeta40 and Abeta42 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 Abeta42/Abeta40 ratios are at increased risk of developing AD during aging than those with higher ratios.

Authors+Show Affiliations

Department of Developmental Neurobiology, Department of Infant Development, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314-6399, United States. pdmehta@worldnet.att.netNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17275850

Citation

Mehta, Pankaj D., et al. "Increased Amyloid Beta Protein Levels in Children and Adolescents With Down Syndrome." Journal of the Neurological Sciences, vol. 254, no. 1-2, 2007, pp. 22-7.
Mehta PD, Capone G, Jewell A, et al. Increased amyloid beta protein levels in children and adolescents with Down syndrome. J Neurol Sci. 2007;254(1-2):22-7.
Mehta, P. D., Capone, G., Jewell, A., & Freedland, R. L. (2007). Increased amyloid beta protein levels in children and adolescents with Down syndrome. Journal of the Neurological Sciences, 254(1-2), 22-7.
Mehta PD, et al. Increased Amyloid Beta Protein Levels in Children and Adolescents With Down Syndrome. J Neurol Sci. 2007 Mar 15;254(1-2):22-7. PubMed PMID: 17275850.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increased amyloid beta protein levels in children and adolescents with Down syndrome. AU - Mehta,Pankaj D, AU - Capone,George, AU - Jewell,Amy, AU - Freedland,Robert L, Y1 - 2007/02/02/ PY - 2006/06/23/received PY - 2006/12/01/revised PY - 2006/12/04/accepted PY - 2007/2/6/pubmed PY - 2007/5/30/medline PY - 2007/2/6/entrez SP - 22 EP - 7 JF - Journal of the neurological sciences JO - J Neurol Sci VL - 254 IS - 1-2 N2 - BACKGROUND: Persons with Down syndrome (DS) (40 years and older) have neuropathological changes characteristic of Alzheimer disease (AD). Soluble forms of amyloid beta (Abeta) peptide generated from amyloid precursor protein (APP) end at C-terminal residues 40 and 42. The presence of the apolipoprotein E (ApoE) epsilon4 allele is a significant risk factor for the development of sporadic AD. Although preliminary studies have shown an association of plasma Abeta42 and ApoE epsilon4 allele in older persons with DS who have dementia, the relationship between plasma Abeta40 and Abeta42 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 Abeta40, Abeta42, 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 Abeta40 and Abeta42, and neopterin levels were quantitated by sandwich ELISA. RESULTS: Abeta40 and Abeta42 levels were higher in DS than controls. The ratio of Abeta42/Abeta40 was lower in DS than in controls. There were significant negative correlations between age and Abeta40 in DS and controls, and between age and Abeta42 levels in DS but not in controls. There was no association of Abeta40 or Abeta42 levels with Apo E in either group. Neopterin levels were higher in DS than controls, and the levels were not correlated with Abeta40 and Abeta42 levels in DS or controls. CONCLUSIONS: The over expression of APP gene in DS leads to increases in plasma Abeta40 and Abeta42 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 Abeta42/Abeta40 ratios are at increased risk of developing AD during aging than those with higher ratios. SN - 0022-510X UR - https://www.unboundmedicine.com/medline/citation/17275850/Increased_amyloid_beta_protein_levels_in_children_and_adolescents_with_Down_syndrome_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-510X(06)00580-6 DB - PRIME DP - Unbound Medicine ER -