Growth Hormone and Insulin-Like Growth Factor-I in Alzheimer's Disease

Abstract

Alzheimer s disease (AD) is a major public health issue in the ageing population. For decades, research focused on studies using neurochemistry and biochemistry to understand the mechanisms underlying this disease. Recently, emerging evidence supports the concept that AD is also a disorder of metabolic degeneration. Amyloid beta-peptide is central to the pathogenesis of AD, and the AD brain is under intense oxidative stress, including membrane lipid peroxidation. Amyloid beta-peptide causes oxidative stress and neurotoxicity to neurons. Neurochemical changes in the brain from patients with AD indicate multiple disturbances and it seems likely that the changes are secondary to more fundamental changes into the brain. Based on decreased IGF-I concentrations in AD, some authors have suggested that disrupted IGF-I input to the brain may be involved in the pathogenesis of amyloidosis and changed IGF-I signalling may potentially lead to amyloidosis. Disrupting IGF-I signalling in the coroid plexus is sufficient to trigger pathological changes as those observed in AD and brain -amyloid increases as consequence of its lower clearance. The IGF-I is a potent neurotrophic as well neuroprotective factor found in the brain with a wide range of actions in both central and peripheral nervous system. IGF-I is a critical promoter of brain development and neuronal survival and plays a role in neuronal rescue during degenerative diseases. So, an emerging clinical targets for improving the quality of life with ageing or for improving clinical manifestations of AD may be activation of GH/IGF-I that rejuvenate the axis to result in overall physiological benefit, with a potential of prevent or reverse detrimental age-related or AD changes in the brain.