Selective increase in cellular A beta 42 is related to apoptosis but not necrosis

Amyloid beta protein ending at 42 (A beta 42) plays an important role in th e pathology of Alzheimer's disease (AD). Here we show an increase in cellul ar A beta 42 in damaged neurons, with both ELISA and immunocytochemistry. T he cellular A beta 42 increase was caused by 3-day treatments with H2O2. et oposide or melphalan, all of which induce genotoxic apoptosis, but not by t reatment with sodium azide, which causes necrosis. Secreted A beta was simi larly decreased with all these treatments. The cellular A beta 42 increase appeared even with minimal damage (ELISA) and A beta 42-positive cells were TUNEL negative (double staining), indicating that any early apoptosis mech anism may induce the cellular A beta 42 increase. Thus, neuronal apoptosis and cellular A beta 42 increase may be linked in a way that contributes imp ortantly to AD pathology. NeuroReport 11:167-171 (C) 2000 Lippincott Willia ms & Wilkins.