Biomarkers of Alzheimer Disease, Insulin Resistance, and Obesity in Childhood

OBJECTIVE: To answer the question of whether onset of insulin resistance (IR) early in life enhances the risk of developing dementia and Alzheimer disease (AD), serum levels of 2 molecules that are likely associated with development of AD, the amyloid beta-protein 42 (A beta 42) and presenilin 1 (PSEN1), were estimated in 101 preschoolers and 309 adolescents of various BMI. METHODS: Participants (215 boys; 48.8%) were normal weight (n = 176; 40%), overweight (n = 135; 30.7%), and obese (n = 129; 29.3%). The HOmeostasis Model of IR (HOMA-IR), HOMA percent beta-cell function (HOMA-beta) and QUantitative Insulin-sensitivity Check Index (QUICKI) were calculated. RESULTS: Obese adolescents had values of Ab42 higher than overweight and normal-weight peers (190.2 +/- 9.16 vs 125.9 +/- 7.38 vs 129.5 +/- 7.65 pg/mL; P<.0001) as well as higher levels of PSEN1 (2.34 +/- 0.20 vs 1.95 +/- 0.20 vs 1.65 +/- 0.26 ng/mL; P<.0001). Concentrations of A beta 42 were significantly correlated with BMI (rho = 0.262; P<.0001), HOMA-IR (rho = 0.261; P<.0001) and QUICKI (rho = 20.220; P<.0001). PSEN1 levels were correlated with BMI (rho = 0.248; P<.0001), HOMA-IR (rho = 0.242; P<.0001), and QUICKI (rho = 20.256; P<.0001). Western blot analysis confirmed that PSEN1 assays measured the full-length protein. CONCLUSION: Obese adolescents with IR present higher levels of circulating molecules that might be associated with increased risk of developing later in elderly cognitive impairment, dementia, and AD.