title: Blockade of the insulin-like growth factor I receptor in the choroid plexus originates Alzheimer's-like neuropathology in rodents: new cues into the human disease?
abstract: The possibility that perturbed insulin/insulin-like growth factor I (IGF-I) signalling is involved in development of late-onset forms of Alzheimer's disease (AD) is gaining increasing attention. We recently reported that circulating IGF-I participates in brain amyloid beta (Abeta) clearance by modulating choroid plexus function. We now present evidence that blockade of the IGF-I receptor in the choroid plexus originates changes in brain that are reminiscent of those found in AD. In rodents, IGF-I receptor impairment led to brain amyloidosis, cognitive disturbance, and hyperphosphorylated tau deposits together with other changes found in Alzheimer's disease such as gliosis and synaptic protein loss. While these disturbances were mostly corrected by restoring receptor function, blockade of the IGF-I receptor exacerbated AD-like pathology in old mutant mice already affected of brain amyloidosis and cognitive derangement. These findings may provide new cues into the causes of late-onset Alzheimer's disease in humans giving credence to the notion that an abnormal age-associated decline in IGF-I input to the choroid plexus may contribute to development of AD in genetically prone subjects.
authors.affiliation: Laboratory of Neuroendocrinology, Cajal Institute, CSIC, Avda. Dr. Arce 37, 28002 Madrid, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Carro
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Trejo
authors.forename: Carlos
authors.initials: C
authors.lastname: Spuch
authors.forename: Delphine
authors.initials: D
authors.lastname: Bohl
authors.forename: Jean Michel
authors.initials: JM
authors.lastname: Heard
authors.forename: Ignacio
authors.initials: I
authors.lastname: Torres-Aleman
mesh_terms: D000375:Aging; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000378:metabolism* / Q000523:psychology; D000818:Animals; D015153:Blotting, Western; D018929:Cell Culture Techniques; D002831:Choroid Plexus / Q000166:cytology / Q000378:metabolism*; D004847:Epithelial Cells; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D049452:Green Fluorescent Proteins; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000172:deficiency; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D017526:Receptor, IGF Type 1 / Q000097:blood / Q000378:metabolism*; D015398:Signal Transduction; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016875:tau Proteins; D049452:Green Fluorescent Proteins; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D038362:Glycogen Synthase Kinase 3