-glutamylcysteinyl synthetase, potentiated the toxic effects of 22C11. It was also demonstrated that selective application to compartmental cultures of hippocampal neurons of 22C11 caused local neuritic degeneration that was prevented by the addition of GEF to the neuritic compartment. Overall, the results showed that the binding of a monoclonal antibody to APP initially triggers neurite degeneration that is followed by capsase-dependent apoptosis in neuronal cultures and illustrates a property of this protein in neurons that may contribute to the profound neuronal cell death associated with Alzheimer=s disease.
Several lines of evidence suggest that beta-amyloid is directly involved in the neuropathology seen in familial and sporadic Alzheimer=s disease. The hallmarks of Alzheimer=s pathology are extracellular plaques containing beta-amyloid, dystrophic neurites, activated microglia, reactive astrocytes, and neuronal loss (Weldon, Maggio, and Mantyh, 1997). A strong correlation has been found between the amount of amyloid found in the brains of Al
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