Cdk5 is a key factor in tau aggregation and tangle formation in vivo

Wendy Noble, Vicki Olm, Kazuyuki Takata, Evelyn Casey, O. Mary, Jordana Meyerson, Kate Gaynor, John LaFrancois, Lili Wang, Takayuki Kondo, Peter Davies, Mark Burns, Veeranna, Ralph Nixon, Dennis Dickson, Yasuji Matsuoka, Michael Ahlijanian, Lit Fui Lau, Karen Duff

Research output: Contribution to journalArticlepeer-review

382 Scopus citations

Abstract

Tau aggregation is a common feature of neurodegenerative diseases such as Alzheimer's disease, and hyperphosphorylation of tau has been implicated as a fundamental pathogenic mechanism in this process. To examine the impact of cdk5 in tau aggregation and tangle formation, we crossed transgenic mice overexpressing the cdk5 activator p25, with transgenic mice overexpressing mutant (P301L) human tau. Tau was hyperphosphorylated at several sites in the double transgenics, and there was a highly significant accumulation of aggregated tau in brainstem and cortex. This was accompanied by increased numbers of silver-stained neurofibrillary tangles (NFTs). Insoluble tau was also associated with active GSK. Thus, cdk5 can initiate a major impact on tau pathology progression that probably involves several kinases. Kinase inhibitors may thus be beneficial therapeutically.

Original languageEnglish (US)
Pages (from-to)555-565
Number of pages11
JournalNeuron
Volume38
Issue number4
DOIs
StatePublished - May 22 2003

ASJC Scopus subject areas

  • Neuroscience(all)

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