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