title: Cdk5 is a key factor in tau aggregation and tangle formation in vivo.
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.
authors.affiliation: Center for Dementia Research, Nathan S. Kline Institute, New York University, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA.
authors.forename: Wendy
authors.initials: W
authors.lastname: Noble
authors.forename: Vicki
authors.initials: V
authors.lastname: Olm
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Takata
authors.forename: Evelyn
authors.initials: E
authors.lastname: Casey
authors.forename: O
authors.initials: O
authors.lastname: Mary
authors.forename: Jordana
authors.initials: J
authors.lastname: Meyerson
authors.forename: Kate
authors.initials: K
authors.lastname: Gaynor
authors.forename: John
authors.initials: J
authors.lastname: LaFrancois
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kondo
authors.forename: Peter
authors.initials: P
authors.lastname: Davies
authors.forename: Mark
authors.initials: M
authors.lastname: Burns
authors.lastname: Veeranna
authors.forename: Ralph
authors.initials: R
authors.lastname: Nixon
authors.forename: Dennis
authors.initials: D
authors.lastname: Dickson
authors.forename: Yasuji
authors.initials: Y
authors.lastname: Matsuoka
authors.forename: Michael
authors.initials: M
authors.lastname: Ahlijanian
authors.forename: Lit-Fui
authors.initials: LF
authors.lastname: Lau
authors.forename: Karen
authors.initials: K
authors.lastname: Duff
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000378:metabolism* / Q000473:pathology; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism*; D004790:Enzyme Induction / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D016874:Neurofibrillary Tangles / Q000201:enzymology*; D010766:Phosphorylation; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D016875:tau Proteins; D051360:Cyclin-Dependent Kinase 5; C495905:CDK5 protein, human; C495906:Cdk5 protein, mouse; D018844:Cyclin-Dependent Kinases; D038362:Glycogen Synthase Kinase 3