Increased intrathecal levels of the angiogenic factors VEGF and TGF-beta in Alzheimer's disease and vascular dementia.

The aim of the present study was to investigate, in patients with Alzheimer's disease (AD), and vascular dementia (VAD), patterns of local release of vascular endothelial growth factor (VEGF) and transforming growth factor-beta (TGF-beta), two cytokines having a pivotal role in hypoxia-induced angiogenesis. The intrathecal levels of these molecules were related to the clinical severity of these diseases and to the intrathecal levels of beta-amyloid protein. Significantly increased cerebrospinal fluid (CSF) levels of both VEGF and TGF-beta were observed in 20 patients with AD and in 26 patients with VAD compared to healthy controls. Interestingly, there was significant correlation between the CSF levels of TGF-beta and VEGF in all the individuals studied. Our study demonstrates, both in patients with AD and in patients with VAD, an intrathecal production of VEGF, a cytokine which plays a pivotal role in angiogenesis. These results suggest that vascular factors might not only play a role in the pathogenesis of VAD but also in the pathogenesis of AD. In addition, we show in AD and VAD an intrathecal production of TGF-beta, a cytokine exerting on one hand anti-inflammatory and angiogenic properties, but on the other promoting amyloidogenesis.