vascular endothelial growth factor vegf affects processing of amyloid precursor protein and betaamyloidogenesis in brain slice cultures derived from transgenic tg2576 mouse brain the upregulation of the angiogenic vascular endothelial growth factor vegf in brains of alzheimer patients in close relationship to betaamyloid abeta plaques suggests a link of vegf action and processing of the amyloid precursor protein app to reveal whether vegf may affect app processing brain slices derived from 17monthold transgenic tg2576 mice were exposed with 1ngml vegf for 6 24 and 72h followed by assessing cytosolic and membranebound app expression level of both soluble and fibrillar abetapeptides as well as activities of alpha and betasecretases in brain slice tissue preparations treatment of brain slices with vegf did not significantly affect the expression level of app regardless of the exposure time studied in contrast vegf exposure of brain slices for 6h reduced the formation of soluble sds extractable abeta140 and abeta142 as compared to brain slice cultures incubated in the absence of any drug while the fibrillar abeta peptides did not change significantly this effect was less pronounced 24h after vegf exposure but was no longer detectable when brain slices were exposed by vegf for 72h which indicates an adaptive response to chronic vegf exposure the vegfmediated reduction in abeta formation was accompanied by a transient decrease in betasecretase activity peaking 6h after vegf exposure to reveal whether the vegfinduced changes in soluble abetalevel may be due to actions of vegf on abeta fibrillogenesis the fibrillar status of abeta was examined using the thioflavint binding assay incubation of abeta preparations obtained from tg2576 mouse brain cortex in the presence of vegf slightly decreased the fibrillar content with increasing incubation time up to 72h the data demonstrate that vegf may affect app processing at least in vitro suggesting a role of vegf in the pathogenesis of alzheimers disease