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?

Authors: Carro, E  Trejo, JL  Spuch, C  Bohl, D  Heard, JM  Torres-Aleman, I 
Citation: Carro E, etal., Neurobiol Aging. 2006 Nov;27(11):1618-31. Epub 2005 Nov 7.
Pubmed: (View Article at PubMed) PMID:16274856
DOI: Full-text: DOI:10.1016/j.neurobiolaging.2005.09.039

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.


Disease Annotations
Objects Annotated

Additional Information

CRRD Object Information
CRRD ID: 10045879
Created: 2015-06-19
Species: All species
Last Modified: 2015-06-19
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.