title: Serum insulin-like growth factor I regulates brain amyloid-beta levels.
abstract: Levels of insulin-like growth factor I (IGF-I), a neuroprotective hormone, decrease in serum during aging, whereas amyloid-beta (Abeta), which is involved in the pathogenesis of Alzheimer disease, accumulates in the brain. High brain Abeta levels are found at an early age in mutant mice with low circulating IGF-I, and Abeta burden can be reduced in aging rats by increasing serum IGF-I. This opposing relationship between serum IGF-I and brain Abeta levels reflects the ability of IGF-I to induce clearance of brain Abeta, probably by enhancing transport of Abeta 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 Abeta burden, we consider that circulating IGF-I is a physiological regulator of brain amyloid levels with therapeutic potential.
authors.affiliation: Laboratory of Neuroendocrinology, Cajal Institute, CSIC, Madrid, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Carro
authors.forename: J L
authors.initials: JL
authors.lastname: Trejo
authors.forename: T
authors.initials: T
authors.lastname: Gomez-Isla
authors.forename: D
authors.initials: D
authors.lastname: LeRoith
authors.forename: I
authors.initials: I
authors.lastname: Torres-Aleman
mesh_terms: D016229:Amyloid beta-Peptides / Q000032:analysis* / Q000378:metabolism; D000818:Animals; D001812:Blood-Brain Barrier; D001923:Brain Chemistry; D002831:Choroid Plexus / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors / Q000502:physiology*; D051379:Mice; D011228:Prealbumin / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; D011228:Prealbumin; D014409:Tumor Necrosis Factor-alpha; D007334:Insulin-Like Growth Factor I