Brain levels of CDK5 activator p25 are not increased in Alzheimer's or other neurodegenerative diseases with neurofibrillary tangles
Article first published online: 4 JUL 2003
Journal of Neurochemistry
Volume 86, Issue 3, pages 572–581, August 2003
How to Cite
Tandon, A., Yu, H., Wang, L., Rogaeva, E., Sato, C., Chishti, M. A., Kawarai, T., Hasegawa, H., Chen, F., Davies, P., Fraser, P. E., Westaway, D. and St George-Hyslop, P. H. (2003), Brain levels of CDK5 activator p25 are not increased in Alzheimer's or other neurodegenerative diseases with neurofibrillary tangles. Journal of Neurochemistry, 86: 572–581. doi: 10.1046/j.1471-4159.2003.01865.x
- Issue published online: 4 JUL 2003
- Article first published online: 4 JUL 2003
- Received February 10, 2003; revised manuscript received April 9, 2003; accepted April 15, 2003.
- neurofibrillary tangles;
Elevated levels of p25 and constitutive activation of CDK5 have been observed in AD brains. This has led to the hypothesis that increased p25 levels could promote neurofibrillary tangles (NFT) through CDK5-mediated hyperphosphorylation of tau, the principal component of NFTs. We examined p25 immunoreactivity in brains from sporadic and familial AD cases, as well as other neurologic diseases that exhibit NFT, such as Down's syndrome (DS), Pick's disease (Pick), corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), frontotemporal dementia (FTD). Neither the p25 immunoreactivity nor the p25/p35 ratio was elevated in the AD brains or in the other tauopathies (n = 34) compared with controls (n = 11). Although Aβ peptides have been suggested to activate calpain-mediated cleavage of p35 to p25 in cultured neurons, p25 levels in brains of TgCRND8 mice, which express high levels of brain Aβ peptides, were similar to those of non-Tg littermates. Our data suggest that high Aβ levels in brain do not activate p35 proteolysis, and p25 is unlikely to be a causative agent for NFT formation in AD or other tauopathies.