Alzheimer's Biomarkers Elevated in Obese Teenagers

Beth Skwarecki

May 11, 2015

Teenagers with insulin resistance had higher levels of two proteins, Aβ42 and PSEN1, thought to be predictive of Alzheimer's disease. Elevated levels were more common in obese teenagers than in those who were overweight or normal weight, but the same correlation was not seen in preschoolers.

"The clinical meaning of this observation is unclear, and longitudinal studies may be helpful to this regard," write Rosa Luciano, MSc, from the Department of Laboratory Medicine, Bambino Gesu Children's Hospital in Rome, Italy, and colleagues. The results were published online May 11 in Pediatrics.

Alzheimer's disease involves dysfunctional insulin signaling in the brain, and patients with type 2 diabetes are more likely to develop dementia. Luciano and colleagues considered the possibility that associations among obesity, insulin resistance, and brain abnormalities may begin in childhood.

The peptide Aβ42 is the longer, more fibrous form of amyloid beta that forms the characteristic deposits in the brains of patients with Alzheimer's. The other biomarker used in the study, PSEN1, is part of a complex that produces the Aβ42 peptide and may be involved in insulin resistance in the brain. Previous studies in elderly populations have found elevated levels of Aβ42 in people who went on to develop Alzheimer's disease, although no studies have verified the accuracy of using Aβ42 to predict dementia.

Dr Luciano and colleagues analyzed blood samples from white preschoolers (age range, 2.0 - 5.8 years) and adolescents (age range, 12.0 - 17.8 years) who enrolled in two other studies at the Gesu Bambino Children's Hospital in Rome. Children were excluded if they had chronic illness, endocrine disorders, or a recent infection causing inflammation or if they were taking drugs that affect growth and carbohydrate metabolism.

Obese teenagers had higher levels of PSEN1 than overweight or normal weight teenagers (P < .0001), as well as higher levels of Aβ42 (ρ = 0.262; P < .0001). Statistical analysis showed, however, that the two biomarkers correlated with insulin resistance (as measured by the homeostasis model of insulin resistance, a calculation based on fasting insulin and fasting glucose) independent of body mass index z-score.

Preschoolers showed no association between body mass index and either Aβ42 or PSEN1, and preschoolers' levels were overall lower than adolescents (P = .0002 for age trend of Aβ42).

Although the results do not indicate whether the children tested will develop diabetes or Alzheimer's disease, the investigators note that the association between Aβ42 and obesity in adolescents but not preschoolers "[suggests] that overweight and obesity accelerate release of serum Aβ42."

The authors have disclosed no relevant financial relationships.

Pediatrics. Published online May 11, 2015.

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