FAD mutants unable to increase neurotoxic Aβ 42 suggest that mutation effects on neurodegeneration may be independent of effects on Aβ
Article first published online: 29 NOV 2006
Journal of Neurochemistry
Volume 101, Issue 3, pages 674–681, May 2007
How to Cite
Shioi, J., Georgakopoulos, A., Mehta, P., Kouchi, Z., Litterst, C. M., Baki, L. and Robakis, N. K. (2007), FAD mutants unable to increase neurotoxic Aβ 42 suggest that mutation effects on neurodegeneration may be independent of effects on Aβ. Journal of Neurochemistry, 101: 674–681. doi: 10.1111/j.1471-4159.2006.04391.x
- Issue published online: 29 NOV 2006
- Article first published online: 29 NOV 2006
- Received August 21, 2006; revised manuscript received October 24, 2006; accepted October 26, 2006.
- Alzheimer’s disease;
- familial Alzheimer’s disease mutation;
Strong support for a primary causative role of the Aβ peptides in the development of Alzheimer’s disease (AD) neurodegeneration derives from reports that presenilin familial AD (FAD) mutants alter amyloid precursor protein processing, thus increasing production of neurotoxic Aβ 1–42 (Aβ 42). This effect of FAD mutants is also reflected in an increased ratio of peptides Aβ 42 over Aβ 1–40 (Aβ 40). In the present study, we show that several presenilin 1 FAD mutants failed to increase production of Aβ 42 or the Aβ 42/40 ratio. Our data suggest that the mechanism by which FAD mutations promote neurodegeneration and AD may be independent of their effects on Aβ production.