Selective increase in cellular Aβ42 is related to apoptosis ... : NeuroReport (original) (raw)
NEUROCHEMISTRY
Ohyagi, Yasumasa2,5; Yamada, Takeshi2; Nishioka, Kenichi3; Clarke, Nigel J.4; Tomlinson, Andy J.4; Naylor, Stephen4; Nakabeppu, Yusaku3; Kira, Jun-ichi2; Younkin, Steven G.1
1Department of Pharmacology, Mayo Clinic Jacksonville, 4500 San Pablo Rd, Jacksonville, FL 32224, USA
2Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812–8582, Japan
3Department of Biochemistry, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812–8582, Japan
4Biomedical Mass Spectrometry Facility, Department of Biochemistry and Molecular Biology, Mayo Clinic Rochester, 200 1 st St. SW, Rochester, MN 55905, USA.
5Corresponding Author: Yasumasa Ohyagi
Acknowledgments: We thank N. Suzuki (Takeda, Co.) for BAN-50, BC-05, and BA-27. Supported by the John Douglas French Alzheimer Foundation, Grant-in-Aid for Scientific Research (Japan Ministry of Education, Culture and Science), Health Science Research Grants (Japan Ministry of Health and Welfare), the Kyushu University Interdisciplinary Programs in Education and Projects in Research Development, and National Institute of Health.
Received 15 September 1999; accepted 3 November 1999
Abstract
Amyloid β protein ending at 42 (Aβ42) plays an important role in the pathology of Alzheimer's disease (AD). Here we show an increase in cellular Aβ42 in damaged neurons, with both ELISA and immunocytochemistry. The cellular Aβ42 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 Aβ was similarly decreased with all these treatments. The cellular Aβ42 increase appeared even with minimal damage (ELISA) and Aβ42-positive cells were TUNEL negative (double staining), indicating that any early apoptosis mechanism may induce the cellular Aβ42 increase. Thus, neuronal apoptosis and cellular Aβ42 increase may be linked in a way that contributes importantly to AD pathology.
© 2000 Lippincott Williams & Wilkins, Inc.