THE INSULIN-LIKE GROWTH-FACTOR-I SYSTEM IN CEREBELLAR DEGENERATION

Brain insulin-like growth factor I (IGF-I) and its related molecules m ay be involved in neurodegenerative processes in which IGF-I-containin g pathways are compromised. Since IGF-I is present in the olivocerebel lar circuitry, two types of late-onset cerebellar ataxias (olivopontoc erebellar and idiopathic cerebellar cortical atrophy) were chosen to t est this hypothesis. The following significant changes in the peripher al IGF-I system of these patients were found: low IGF-I levels, and hi gh IGF-binding protein 1 (BP-1), and BP-3 affinity for IGF-1. Sixty pe rcent of the patients also had significantly low insulin levels. Patie nts suffering from other neurological diseases with cerebellar dysfunc tion and ataxia not involving the olivocerebellar pathway also had low IGF-I levels, while IGFBPs and insulin levels were normal. Our data i ndicate that degeneration of an IGF-I-containing neuronal pathway prod uces significant changes in the peripheral IGF system. This suggests s trongly that the endocrine (bloodborne) and the paracrine/autocrine (b rain) IGF systems are linked functionally. We propose that alterations in the blood IGF-I system may constitute a marker of some cerebellar diseases.