Insulin-like growth factor binding proteins in cerebrospinal fluid during human development and aging

We analyzed samples of insulin-like growth factor binding proteins (IGFBPs) in human cerebrospinal fluid (CSF) in neurologically normal patients from one day after birth to age 76 years. CSF samples were separated on SDS-PAGE and then transferred to nitrocellulose membranes where IGFBPs were detected by Western ligand blot using [(125)I]-IGF-II, confirming other reports where we found the presence of IGFBP-2, 3, 4, 5. The 34 kDa IGFBP-2 was present in all samples, and progressively decreased with age. A broad 28- to 30-kDa IGFBP band, having the appearance of IGFBP-5, was triphasic: faint during infancy, barely detectable at 6 months, but intense in adult and aged individuals. The 24-kDa IGFBP-4 band was only seen in neonatal CSF samples, while the IGFBP-3 doublet gradually increased during aging. Thus, these present results show that IGFBP-2, 3, 4 and 5 in CSF are developmentally regulated, suggesting roles for these molecules in the development of the nervous system.