Targeting insulin-like growth factor-1 to treat Alzheimer's disease

Abstract

The ‘amyloid cascade hypothesis’ proposes that disturbances in amyloid metabolism cause Alzheimer's disease (AD). However, a comprehensive explanation of the mechanisms leading to brain amyloidosis is still pending. Building on previous findings with insulin, and recent observations with insulin-like growth factor-1 (IGF-1) in AD pathology, new evidence suggests that the interaction of environmental factors and inheritance lead to abnormally reduced input/traffic of serum IGF-1 at the blood–brain barriers. The resultant deterioration in brain IGF-1 function may originate all the pathological changes observed in late-onset AD. These include cognitive loss, abnormal amyloid metabolism and aberrant Tau phosphorylation, as well as disturbances, such as inflammation, oxidative stress or mitochondrial dysfunction, among others. A better understanding of the role of IGF-1 in all these perturbations is required, particularly in relation to cognition. Furthermore, insight into the environmental factors contributing to abnormally reduced IGF-1 function in AD brains may become crucial in development of much needed disease-modifying strategies.

Keywords::

• Alzheimer's disease
• amyloidosis
• cognitive loss
• insulin-like growth factor I
• tauopathy

Acknowledgements

The essential contribution of present and past members of the lab to the findings discussed herein is acknowledged.

Notes