title: Selective increase in cellular A beta 42 is related to apoptosis but not necrosis.
abstract: Amyloid beta protein ending at 42 (A beta 42) plays an important role in the pathology of Alzheimer's disease (AD). Here we show an increase in cellular A beta 42 in damaged neurons, with both ELISA and immunocytochemistry. The cellular A beta 42 increase was caused by 3-day treatments with H2O2, etoposide or melphalan, all of which induce genotoxic apoptosis, but not by treatment with sodium azide, which causes necrosis. Secreted A beta was similarly 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 mechanism 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 importantly to AD pathology.
authors.affiliation: Department of Pharmacology, Mayo Clinic Jacksonville, FL 32224, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Ohyagi
authors.forename: T
authors.initials: T
authors.lastname: Yamada
authors.forename: K
authors.initials: K
authors.lastname: Nishioka
authors.forename: N J
authors.initials: NJ
authors.lastname: Clarke
authors.forename: A J
authors.initials: AJ
authors.lastname: Tomlinson
authors.forename: S
authors.initials: S
authors.lastname: Naylor
authors.forename: Y
authors.initials: Y
authors.lastname: Nakabeppu
authors.forename: J
authors.initials: J
authors.lastname: Kira
authors.forename: S G
authors.initials: SG
authors.lastname: Younkin
mesh_terms: D016229:Amyloid beta-Peptides / Q000096:biosynthesis*; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005047:Etoposide / Q000494:pharmacology; D006168:Guinea Pigs; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008558:Melphalan / Q000494:pharmacology; D009336:Necrosis; D010446:Peptide Fragments / Q000096:biosynthesis*; D017382:Reactive Oxygen Species / Q000378:metabolism; D019810:Sodium Azide / Q000633:toxicity
chemical_list: D016229:Amyloid beta-Peptides; D018906:Antineoplastic Agents, Alkylating; D000972:Antineoplastic Agents, Phytogenic; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; C075222:amyloid beta-protein (1-42); D005047:Etoposide; D019810:Sodium Azide; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D008558:Melphalan