The pro-form of nerve growth factor (pro-NGF) has been shown to be a high affinity ligand for p75NTR and to induce apoptosis through this receptor. It has been reported that pro-NGF, rather than mature NGF, is the predominant form of this neurotrophin in human brain. In the present work we studied the potential involvement of pro-NGF purified from human brains affected by Alzheimer's disease (AD), where it is especially abundant, in the neuronal apoptosis observed in this disease. Western blot analysis of human brain tissue showed the existence of several pro-NGF forms. Some of these pro-NGF forms were significantly increased in AD brain cortex in a disease stage-dependent manner. Pro-NGF, purified by chromatography from human AD brains, induced apoptotic cell death in sympathetic neurons and in a p75NTR stably transfected cell line. Blocking p75NTR in cell culture abolished neuronal apoptosis caused by pro-NGF. p75NTR-transfected cells underwent apoptosis in the presence of pro-NGF while control wild-type cells did not. Taken together, these results indicate that pro-NGF purified from AD human brains can induce apoptosis in neuronal cell cultures through its interaction with the p75NTR receptor.

LC is a misdiagnosed entity associated with considerable diagnostic delay. MRI evidence of bilateral hemispheric involvement and CSF pleocytosis should be alerts for this diagnosis. Treatment with methotrexate-based chemotherapy must be considered, especially for patients with good KPS.

Our study failed to provide evidence to support the use of monthly long-acting somatostatin analogue schedule in recurrent high-grade meningiomas, as none of our patients demonstrated RPR. The modest median PFS of 4-5 months along with the unknown natural history of recurrent meningiomas render the use of this therapy against these aggressive brain tumors uncertain.