Neurodegeneration is associated to changes in serum insulin-like growth factors

Serum levels of insulin and insulin-like growth factors and their binding p roteins (IGFs and IGFBPs, respectively) are changed in human neurodegenerat ive diseases of very different etiology, such as Alzheimer's disease, amyot rophic lateral sclerosis, or cerebellar ataxia. However, the significance o f these endocrine disturbances is not clear. We now report that in two very different inherited neurodegenerative conditions, ataxia-telangiectasia (A T) and Charcot-Marie-Tooth 1A (CMT-1A) disease, serum levels of IGFs are al so altered. Both types of patients have increased serum IGF-I and IGFBP-2 l evels, and decreased serum IGFBP-1 levels, while only AT patients have high serum insulin levels. Furthermore, serum IGFs are also changed in three di fferent animal models of neurodegeneration: neurotoxin-induced motor discoo rdination, diabetic neuropathy, and hereditary cerebellar ataxia. In these three models, serum insulin levels are significantly decreased, serum IGF-I and IGFBP-1, -2, and -3 are decreased in diabetic and neurotoxin-injected rats, while serum IGFBP-1 is increased in hereditary ataxic rats. Altogethe r, these observations indicate that a great variety of neurodegenerative di seases show endocrine perturbations, resulting in changes in serum IGFs lev els. These perturbations are disease-specific and are probably due to metab olic and endocrine derangements, nerve cell death, and sickness-related dis turbances associated to the neurodegenerative process. Our observations str ongly support the need to evaluate serum IGFs in other neurodegenerative co nditions. (C) 2000 Academic Press.