Serum IGF-I, Life-style, and Risk of Alzheimer´s disease

PIRIZ J., NISHIJIMA T., TREJO JL. AND TORRES ALEMAN I

Diabetes, Insulin and Alzheimer's Disease

Springer

Lugar: Heidelberg, Alemania; Año: 2010; p. 201 - 213

The ancient insulin-like family of peptides gave rise in higher organisms to insulin-growth factors (IGFs) and insulin. Formerly considered functionally divergent, new evidence suggests that IGFs and insulin probably share a close functional relationship. These links are still poorly defined but may eventually turn out to be of great relevance in the development of Alzheimer´s pathology. IGF-I in the circulation acts as a neuroprotective hormone, entering into the brain through a transport system at the blood-brain barriers. The neuroactive role of serum IGF-I is modulated by environmental factors and behavior. Importantly, both environmental factors and life style are increasingly recognized to impact the development of Alzheimer´s disease (AD). Risk factors classically associated with cardiovascular disease, such as unhealthy diets, lack of physical exercise, or stress, are now also related to AD. The molecular underpinnings of these links are starting to be unveiled. There is evidence pointing to serum IGF-I in this regard. Circumstantial observations, such as that serum IGF-I declines with aging, the single most important risk factor for AD, or that serum IGF-I correlates with cognitive status in humans, have hinted at this connection. Further, diet, and physical or mental activity influence serum IGF-I input to the brain. In addition, stress and general health status may influence brain input of serum IGF-I. All these factors have been linked to a risk of AD. Analysis of the molecular and cellular pathways involved in serum IGF-I traffic at the blood-brain interfaces indicates that pathogenic disturbances at these sites may be of great relevance in the development of AD. Indeed, reduced brain IGF-I input elicits all the neuropathological changes associated with AD. As all the above-mentioned life style factors impinge on the transport of IGF-I at the barriers, a molecular understanding of their role as risk factors is now within reach.