C - Chemistry – Metallurgy – 12 – N
Patent
C - Chemistry, Metallurgy
12
N
C12N 15/16 (2006.01) A01K 67/027 (2006.01) A61K 38/17 (2006.01) A61K 38/22 (2006.01) C07K 14/47 (2006.01) C12N 15/12 (2006.01) C12N 15/79 (2006.01) C12N 15/85 (2006.01)
Patent
CA 2295861
The invention provides transgenic, non-human animals and transgenic non-human mammalian cells harboring a transgene encoding a p25 (activator of the protein kinase cdk 5) polypeptide. The two neuropathological lesions associated with Alzheimer's disease (AD) are amyloid plaques and neurofibrillary tangles (NFTs), composed predominantly of amyloid .beta. peptides and hyperphosphorylated tau, respectively. While animal models for plaque formation exist, there is no animal model that recapitulates the formation of NFTs. This invention provides transgenic mice that overexpress human p25, an activator of cdk5, resulting in tau that is hyperphosphorylated at AD-relevant epitopes. Deposition of tau is detected in the amygdala, thalamus and cortex. Increased phosphorylated neurofilament, silver-positive neurons and neuronal death are also observed in these regions. We conclude that the overexpression of p25, an activator of cdk5, is sufficient to produce hyperphosphorylation of tau and neuronal death. The p25 transgenic mouse represents the first model for tau pathology in AD.
Ahlijanian Michael Kirk
Mcneish John Douglas
Bereskin & Parr Llp/s.e.n.c.r.l.,s.r.l.
Pfizer Products Inc.
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