title: Loss of serum IGF-I input to the brain as an early biomarker of disease onset in Alzheimer mice.
abstract: Circulating insulin-like growth factor I (IGF-I) enters the brain and promotes clearance of amyloid peptides known to accumulate in Alzheimer's disease (AD) brains. Both patients and mouse models of AD show decreased level of circulating IGF-I enter the brain as evidenced by a lower ratio of cerebrospinal fluid/plasma IGF-I. Importantly, in presymptomatic AD mice this reduction is already manifested as a decreased brain input of serum IGF-I in response to environmental enrichment. To explore a potential diagnostic use of this early loss of IGF-I input, we monitored electrocorticogram (ECG) responses to systemic IGF-I in mice. Whereas control mice showed enhanced ECG activity after IGF-I, presymptomatic AD mice showed blunted ECG responses. Because nonhuman primates showed identically enhanced electroencephalogram (EEG) activity in response to systemic IGF-I, loss of the EEG signature of serum IGF-I may be exploited as a disease biomarker in AD patients.
authors.affiliation: 1] Systems Neurobiology, Cajal Institute (CSIC), Madrid, Spain [2] CIBERNED, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Trueba-Sáiz
authors.forename: C
authors.initials: C
authors.lastname: Cavada
authors.forename: A M
authors.initials: AM
authors.lastname: Fernandez
authors.forename: T
authors.initials: T
authors.lastname: Leon
authors.forename: D A
authors.initials: DA
authors.lastname: González
authors.forename: J
authors.initials: J
authors.lastname: Fortea Ormaechea
authors.forename: A
authors.initials: A
authors.lastname: Lleó
authors.forename: T
authors.initials: T
authors.lastname: Del Ser
authors.forename: A
authors.initials: A
authors.lastname: Nuñez
authors.forename: I
authors.initials: I
authors.lastname: Torres-Aleman
mesh_terms: D000544:Alzheimer Disease / Q000097:blood / Q000134:cerebrospinal fluid / Q000175:diagnosis*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D016022:Case-Control Studies; D004195:Disease Models, Animal; D042241:Early Diagnosis; D004569:Electroencephalography / Q000187:drug effects*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000134:cerebrospinal fluid / Q000378:metabolism / Q000494:pharmacology*; D008251:Macaca; D051379:Mice
chemical_list: C583557:IGF1 protein, human; C519530:insulin-like growth factor-1, mouse; D007334:Insulin-Like Growth Factor I