title: Beta-amyloid monomer and insulin/IGF-1 signaling in Alzheimer's disease.
abstract: Alzheimer's disease is the most common form of dementia among older people and is still untreatable. While β-amyloid protein is recognized as the disease determinant with a pivotal role in inducing neuronal loss and dementia, an impaired brain insulin signaling seems to account in part for the cognitive deficit associated with the disease. The origin of this defective signaling is uncertain. Accumulating toxic species of β-amyloid, the so-called oligomers, has been proposed to be responsible for downregulation of neuronal insulin receptors. We have found that the nontoxic form of β-amyloid, the monomer, is able to activate insulin/insulin-like growth factor-1 (IGF-1) receptor signaling and thus behaves as a neuroprotectant agent. Our suggestion is that depletion of β-amyloid monomers, occurring in the preclinical phase of Alzheimer's disease, might be the cause of early insulin/IGF-1 signaling disturbances that anticipate cognitive decline.
authors.affiliation: Institute of Biostructure and Bioimaging, National Research Council, Viale Andrea Doria, Catania 95125, Italy.
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Giuffrida
authors.forename: Flora
authors.initials: F
authors.lastname: Tomasello
authors.forename: Filippo
authors.initials: F
authors.lastname: Caraci
authors.forename: Santina
authors.initials: S
authors.lastname: Chiechio
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Nicoletti
authors.forename: Agata
authors.initials: A
authors.lastname: Copani
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D016229:Amyloid beta-Peptides; D007328:Insulin; D007334:Insulin-Like Growth Factor I