The insulin-like growth factor I system in cerebellar degeneration

Brain insulin-like growth factor I (IGF-I) and its related molecules may be involved in neurodegenerative processes in which IGF-I-containing pathways are compromised. Since IGF-I is present in the olivocerebellar circuitry, two types of late-onset cerebellar ataxias (olivopontocerebellar and idiopathic cerebellar cortical atrophy) were chosen to test this hypothesis. The following significant changes in the peripheral IGF-I system of these patients were found: low IGF-I levels, and high IGF-binding protein 1 (BP-1), and BP-3 affinity for IGF-1. Sixty percent of the patients also had significantly low insulin levels. Patients suffering from other neurological diseases with cerebellar dysfunction and ataxia not involving the olivocerebellar pathway also had low IGF-I levels, while IGFBPs and insulin levels were normal. Our data indicate that degeneration of an IGF-I-containing neuronal pathway produces significant changes in the peripheral IGF system. This suggests strongly that the endocrine (bloodborne) and the paracrine/autocrine (brain) IGF systems are linked functionally. We propose that alterations in the blood IGF-I system may constitute a marker of some cerebellar diseases.