Serum insulin-like growth factor I regulates brain amyloid-[beta] levels

Levels of insulin-like growth factor I (IGF-I), a neuroprotective hormone, decrease in serum during aging, whereas amyloid-[beta] (A[beta]), which is involved in the pathogenesis of Alzheimer disease, accumulates in the brain. High brain A[beta] levels are found at an early age in mutant mice with low circulating IGF-I, and A[beta] burden can be reduced in aging rats by increasing serum IGF-I. This opposing relationship between serum IGF-I and brain A[beta] levels reflects the ability of IGF-I to induce clearance of brain A[beta], probably by enhancing transport of A[beta] carrier proteins such as albumin and transthyretin into the brain. This effect is antagonized by tumor necrosis factor-[alpha], a pro-inflammatory cytokine putatively involved in dementia and aging. Because IGF-I treatment of mice overexpressing mutant amyloid markedly reduces their brain A[beta] burden, we consider that circulating IGF-I is a physiological regulator of brain amyloid levels with therapeutic potential.
Author(s): E. Carro [1]; J.L. Trejo [1]; T. Gomez-Isla [2]; D. LeRoith [3]; I. Torres-Aleman (corresponding author) [1] Insulin and insulin-like growth factor I (IGF-I) are structurally related circulating hormones. [...]