Obese adolescents with insulin resistance at elevated risk for Alzheimer’s disease

Adolescents with insulin resistance who were overweight or obese exhibited high serum levels of circulating amyloid B-protein 42 and presenilin 1, molecules associated with an increased risk for Alzheimer’s disease and dementia later in life, according to recent study findings.

Based on previous research reported in the study, insulin resistance plays a key role in obesity and recently has been suggested to increase the risk for Alzheimer’s disease.

Rosa Luciano, MSc, of the department of laboratory medicine at Bambino Gesù Children’s Hospital in Rome, and colleagues sought to assess whether the onset of insulin resistance early in life increased the risk for dementia and Alzheimer’s disease. The researchers estimated the serum levels of amyloid B-protein 42 (AB42) and presenilin 1 (PSEN1) in 101 preschoolers and 309 adolescents with varying BMI levels.

Forty percent of the study cohort was considered normal weight, 30.7% were overweight, and 29.3% were obese. The highest levels of AB42 were observed in obese adolescents (190.2 pg/mL), followed by overweight (125.9 pg/mL) and normal-weight peers (129.5 pg/mL; P < .0001). Obese adolescents also exhibited higher levels of PSEN1 (2.34 ng/mL), followed by 1.95 ng/mL in overweight adolescents and 1.65 ng/mL in normal-weight adolescents (P < .0001).

Significant associations were observed between concentrations of AB42 and BMI (r = 0.262; P < .0001), Homeostasis Model of IR (r = 0.261; P < .0001) and Quantitative Insulin-sensitivity Check Index (r = –0.22; P < .0001).

Levels of PSEN1 also were associated with BMI (r = 0.248; P < .0001), Homeostasis Model of IR (r = 0.242; P < .0001) and Quantitative Insulin-sensitivity Check Index (r = –0.256; P < .0001).

“This is the first report that demonstrates the association between systemic insulin resistance as estimated by the Homeostasis Model of IR and serum concentrations of AB42 and PSEN1 in young individuals,” the researchers wrote. “This association was independent of the BMI z score. Interestingly, concentrations of both AB42 and PSEN1 were significantly higher in overweight and obese adolescents than in normal-weight peers, but not yet in overweight and obese preschoolers as compared with normal-weight preschoolers.”

Disclosure: The study was funded by the Italian Ministry of Health. The researchers report no relevant financial disclosures.