title: Biomarkers of Alzheimer Disease in Children with Obstructive Sleep Apnea: Effect of Adenotonsillectomy.
abstract: Obese children are at increased risk for developing obstructive sleep apnea (OSA), and both of these conditions are associated with an increased risk for end-organ morbidities. Both OSA and obesity (OB) have been associated with increased risk for Alzheimer disease (AD). This study aimed to assess whether OSA and OB lead to increased plasma levels of 2 AD markers amyloid β protein 42 (Aβ42) and pre-senilin 1 (PS1).
  
  
  
  Fasting morning plasma samples from otherwise healthy children with a diagnosis of OB, OSA, or both (OSA+OB), and controls, and in a subset of children with OSA after adenotonsillectomy (T&A) were assayed for Aβ42 and PS1 levels using commercial enzyme-linked immunosorbent assay kits.
  
  
  
  286 children (mean age of 7.2 ± 2.7 y) were evaluated. Compared to control subjects, OB children had similar Aβ42 (108.3 ± 31.7 pg/mL versus 83.6 ± 14.6 pg/mL) and PS1 levels (0.89 ± 0.44 ng/mL versus 0.80 ± 0.29 pg/mL). However, OSA children (Aβ42: 186.2 ± 66.7 pg/mL; P < 0.001; PS1: 3.42 ± 1.46 ng/mL; P < 0.001), and particularly OSA+OB children had significant elevations in both Aβ42 (349.4 ± 112.9 pg/mL; P < 0.001) and PS1 (PS1: 4.54 ± 1.16 ng/mL; P < 0.001) circulating concentrations. In a subset of 24 children, T&A resulted in significant reductions of Aβ42 (352.0 ± 145.2 versus 151.9 ± 81.4 pg/mL; P < 0.0001) and PS1 (4.82 ± 1.09 versus 2.02 ± 1.18 ng/mL; P < 0.0001).
  
  
  
  Thus, OSA, and particularly OSA+OB, are associated with increased plasma levels of AD biomarkers, which decline upon treatment of OSA in a representative, yet not all- encompassing subset of patients, suggesting that OSA may accelerate AD-related processes even in early childhood. However, the cognitive and overall health-related implications of these findings remain to be defined.
authors.affiliation: Section of Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL.
authors.forename: Leila
authors.initials: L
authors.lastname: Kheirandish-Gozal
authors.affiliation: Section of Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL.
authors.forename: Mona F
authors.initials: MF
authors.lastname: Philby
authors.affiliation: Sleep Unit, CIBER of Respiratory Diseases, Instituto Carlos III, CIBERES, Hospital Universitario de Burgos (HUBU), Burgos, Spain.
authors.forename: María Luz
authors.initials: ML
authors.lastname: Alonso-Álvarez
authors.affiliation: Sleep Unit, CIBER of Respiratory Diseases, Instituto Carlos III, CIBERES, Hospital Universitario de Burgos (HUBU), Burgos, Spain.
authors.forename: Joaquin
authors.initials: J
authors.lastname: Terán-Santos
authors.affiliation: Section of Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL.
authors.forename: David
authors.initials: D
authors.lastname: Gozal
mesh_terms: D000233:Adenoidectomy; D000544:Alzheimer Disease / Q000097:blood* / Q000150:complications; D016229:Amyloid beta-Peptides / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005215:Fasting; D005260:Female; D006801:Humans; D008297:Male; D009765:Obesity / Q000097:blood / Q000150:complications / Q000503:physiopathology; D010446:Peptide Fragments / Q000097:blood*; D017286:Polysomnography; D053764:Presenilin-1 / Q000097:blood*; D012189:Retrospective Studies; D020181:Sleep Apnea, Obstructive / Q000097:blood* / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D013851:Thinness / Q000097:blood; D014068:Tonsillectomy
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; D053764:Presenilin-1; C075222:amyloid beta-protein (1-42)
keywords: Alzheimer disease; beta-amyloid; children; inflammation; intermittent hypoxia; obesity; pre-senilin 1; sleep apnea