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, respectvely. 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.
A invenção fornece animais transgenic, non-human e as pilhas mammalian non-human transgenic que abrigam um transgene que codifica um p25 (activador do polypeptide do cdk do kinase de proteína 5). Os dois lesions neuropathological associaram com a doença de Alzheimer (ANÚNCIO) são chapas amyloid e tangles neurofibrillary (NFTs), compostos predominantly do beta amyloid. os peptides e hyperphosphorylated o tau, respectvely. Quando os modelos animais para a formação da chapa existirem, não há nenhum modelo animal que recapitulates a formação de NFTs. Esta invenção fornece os ratos transgenic que os overexpress p25 humano, um activador de cdk5, tendo por resultado o tau que é hyperphosphorylated em epitopes Anúncio-relevantes. O deposition do tau é detectado no amygdala, no thalamus e no cortex. O neurofilament phosphorylated aumentado, os neurônios prata-positivos e a morte neuronal são observados também nestas regiões. Nós conclímos que o overexpression de p25, um activador de cdk5, é suficiente produzir o hyperphosphorylation do tau e da morte neuronal. O rato p25 transgenic representa o primeiro modelo para o pathology do tau no ANÚNCIO.
