Age-related modulation of γ-secretase activity in non-human primate brains
Article first published online: 14 AUG 2012
© 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry
Journal of Neurochemistry
Volume 123, Issue 1, pages 21–28, October 2012
How to Cite
Nishimura, M., Nakamura, S.-i., Kimura, N., Liu, L., Suzuki, T. and Tooyama, I. (2012), Age-related modulation of γ-secretase activity in non-human primate brains. Journal of Neurochemistry, 123: 21–28. doi: 10.1111/j.1471-4159.2012.07884.x
- Issue published online: 10 SEP 2012
- Article first published online: 14 AUG 2012
- Accepted manuscript online: 21 JUL 2012 12:49AM EST
- Received April 17, 2012; revised manuscript received July 11, 2012; accepted July 12, 2012.
- Alzheimer’s disease;
- amyloid-β peptide;
- cynomolgus monkey
Age-dependent accumulation of the amyloid-β peptide (Aβ) in the brain is a pre-condition for development of Alzheimer’s disease. A relative increase in the generation of longer Aβ species such as Aβ42 and Aβ43 is critical for Aβ deposition, but the underlying mechanism remains unresolved. Here, we performed a cell-free assay using microsome fractions of temporal cortex tissues from 42 cynomolgus monkeys and found that Aβ40-generating γ-secretase activity (γ40) decreased with age, whereas Aβ42-generating γ-secretase activity (γ42) was unaltered. In ELISAs, more than 80% of monkeys over 20-years old showed evidence of Aβ accumulation in the temporal cortex. The ratio of γ42 to γ40 increased with age and correlated with the level of accumulated Aβ. These results suggest that γ-secretase activity undergoes age-related, non-genetic modulation and that this modulation may cause Aβ accumulation in aging brains. Similar modulation may predispose aged human brains to Alzheimer’s disease.