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

Abstract

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 β-protein 42 (Aβ42) and presenilin 1 (PSEN1), were estimated in 101 preschoolers and 309 adolescents of various BMI. 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 β-cell function (HOMA-β) and QUantitative Insulin-sensitivity Check Index (QUICKI) were calculated. Obese adolescents had values of Aβ42 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 Aβ42 were significantly correlated with BMI (ρ = 0.262; P < .0001), HOMA-IR (ρ = 0.261; P < .0001) and QUICKI (ρ = -0.220; P < .0001). PSEN1 levels were correlated with BMI (ρ = 0.248; P < .0001), HOMA-IR (ρ = 0.242; P < .0001), and QUICKI (ρ = -0.256; P < .0001). Western blot analysis confirmed that PSEN1 assays measured the full-length protein. 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.