Biomarkers of Alzheimer disease, insulin resistance, and obesity in childhood.

ABSTRACT

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 ß-protein 42 (Aß42) 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 ß-cell function (HOMA-ß) and QUantitative Insulin-sensitivity Check Index (QUICKI) were calculated. RESULTS: Obese adolescents had values of Aß42 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 Aß42 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. 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.