Format

Send to

Choose Destination
Neurosci Res. 1999 May;34(1):21-9.

Elevated neuronal Cdc2-like kinase activity in the Alzheimer disease brain.

Author information

1
Department of Cell Biology and Anatomy, The University of Calgary, Alta, Canada. kylee@acs.ucalgary.ca

Abstract

Neurofibrillary tangles (NFT) in Alzheimer's disease (AD) consist largely of hyperphosphorylated tau protein. Many of the phosphorylation sites on tau are serine/threonine-proline sequences, several of which are phosphorylated in vitro by neuronal Cdc2-like kinase (Nclk), a kinase composed of Cdk5 and its activator(s). Thus, tau hyperphosphorylation in AD may result in part from deregulation of Nclk. To test this hypothesis, we examined Nclk activity in prefrontal and cerebellar cortex from 15 postmortem AD and 16 age-matched control subjects, and corrected either for Cdk5 level or for neuronal loss. The ratio of Nclk activity in prefrontal versus cerebellar cortex was then compared. When corrections were made for neuronal loss, the ratios of kinase activity in prefrontal versus cerebellar cortex were significantly higher in AD (6.45+/-0.86) than the controls (3.13+/-0.46; P = 0.003). This finding is consistent with a role for Nclk in the pathogenesis of NFT in AD.

PMID:
10413323
DOI:
10.1016/s0168-0102(99)00026-7
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center