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Therapeutic actions of insulin-like growth factor I on APP/PS2 mice with severe brain amyloidosis


Year of Publication:
Contact PI Name:
Ignacio Torres-Aleman
Contact PI Affiliation:
Laboratory of Neuroendocrinology Cajal Institute, Madrid, Spain
E. Carro, J.L. Trejo, A. Gerber, H. Loetscher, J. Torrado, F. Metzger
Primary Reference (PubMED ID):
Funding Source:
Not Reported
Study Goal and Principal Findings:

This study investigated effects of  insulin-like growth factor I on brain Aβ levels in APP/PS2 Tg mice. IGF-1 is a neurotrophic hormone that might be involved in the pathogenesis of AD through its ability to regulate brain Aβ  clearance. In this study, treatment of these deteriorated mice with a systemic slow release formulation of IGF-I significantly ameliorated AD-like disturbances. Thus, IGF-I enhanced cognitive performance, decreased brain Aβ  load, increased the levels of synaptic proteins, and reduced astrogliosis associated to Aβ  plaques. The beneficial effects of IGF-I were associated to a significant increase in brain Aβ  complexed to protein carriers such as albumin, apolipoprotein J or transthyretin. This study suggests that accumulation of Aβ  in AD may be due to impaired degradation/clearance rather than increased production. Therefore, enhancement of Aβ clearance through upregulation of Aβ  carriers and transport through the blood-brain-barriers may be of therapeutic benefit in AD related amyloidosis.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Biologic - Hormone
Therapeutic Agent:
Insulin-like Growth Factor 1 (IGF-1)
Therapeutic Target:
Insulin Receptor
Therapeutic Notes:
Insulin Receptor has been nominated as a potential target for AD. Nominated targets are obtained from several sources, including the National Institute on Aging's Accelerating Medicines Partnership in Alzheimer's Disease (AMP-AD) consortium. Targets have been identified using computational analyses of high-dimensional genomic, proteomic and/or metabolomic data derived from human samples. See Agora link for more information.

Animal Model

Model Information:
Model Type:
Strain/Genetic Background:

Experimental Design

Is the following information reported in the study?:
Power/Sample Size Calculation
Randomized into Groups
Blinded for Treatment
Blinded for Outcome Measures
Pharmacokinetic Measures
Pharmacodynamic Measures
Toxicology Measures
ADME Measures
Route of Delivery
Duration of Treatment
Frequency of Administration
Age of Animal at the Beginning of Treatment
Age of Animal at the End of Treatment
Sex as a Biological Variable
Study Balanced for Sex as a Biological Variable
Number of Premature Deaths
Number of Excluded Animals
Statistical Plan
Genetic Background
Inclusion/Exclusion Criteria Included
Conflict of Interest


Outcome Measured
Outcome Parameters
Morris Water Maze
Hidden Platform Task
Brain-beta Amyloid Peptide 40
Brain-beta Amyloid Peptide 42
Brain-Buffer Insoluble beta Amyloid Peptide 40
Brain-Buffer Insoluble beta Amyloid Peptide 42
Brain-Buffer Soluble beta Amyloid Peptide 40
Brain-Buffer Soluble beta Amyloid Peptide 42
Amyloid Precursor Protein (APP)
APP-CTF99 (CTF beta)
Dynamin 1
Apolipoprotein J (ApoJ)
Activated Astrocytes
beta Amyloid Load
Cell Biology
beta Amyloid Peptide Clearance
Blood Brain Barrier Penetration