The invention provides transgenic, non-human animals and transgenic non-human mammalian cells harboring a
transgene encoding a TGII (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 β 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 TGII, 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 TGII, an activator of cdk5, is sufficient to produce
hyperphosphorylation of tau and neuronal death. The TGII transgenic mouse represents the first model for
tau pathology in AD.