Human choroid plexus growth factors: What are the implications for CSF dynamics in Alzheimer's disease?

The choroid plexus plays a key role in supporting neuronal function by secr eting cerebrospinal fluid (CSF) and may be involved in the regulation of va rious soluble factors. Because the choroid plexus is involved in growth fac tor secretion as well as CSF dynamics, it is important to understand how gr owth factors in CSF interact with the brain parenchyma as well as with cell s in direct contact with the flowing CSF, i.e., choroid plexus and arachnoi d villi. While the existence of growth factors in the choroid plexus has be en documented in several animal models, the presence and distribution of gr owth factors in the human choroid plexus has not been extensively examined. This study describes the general distribution and possible functions of a number of key proteins in the human choroid plexus and arachnoid villi, inc luding basic fibroblast growth factor, FGF receptor, and vascular endotheli al growth factor. FGF and VEGF could both be readily demonstrated in choroi d plexus epithelial cells. The presence of FGF and VEGF within the choroid plexus was also confirmed by ELISA analysis. Since Alzheimer's disease (AD) is known to be associated with a number of growth factor abnormalities, we examined the choroid plexus and arachnoid villi from AD patients. Immunohi stochemical studies revealed the presence of FGF and VEGF within the AD cho roid plexus and an increased density of FGFr in both the choroid plexus and the arachnoid villi of AD patients. No qualitative changes in the distribu tion of FGF and VEGF were observed in the AD choroid plexus. The appearance of FGFr in AD arachnoid was associated with robust amyloid and vimentin im munoreactivity. These findings confirm the presence of FGF and VEGF within the normal and AD choroid plexus and suggest that the alteration of growth factors and their receptors may contribute to the pathogenesis of the hydro cephalus ex vacuo that is characteristically seen in AD. (C) 2001 Academic Press.