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Hyperphosphorylation and aggregation of tau in experimental autoimmune encephalomyelitis.

Authors: Schneider, A  Araujo, GW  Trajkovic, K  Herrmann, MM  Merkler, D  Mandelkow, EM  Weissert, R  Simons, M 
Citation: Schneider A, etal., J Biol Chem 2004 Dec 31;279(53):55833-9. Epub 2004 Oct 19.
Pubmed: (View Article at PubMed) PMID:15494405
DOI: Full-text: DOI:10.1074/jbc.M409954200

Axonal damage is a major morphological correlate and cause of permanent neurological deficits in patients with multiple sclerosis (MS), a multifocal, inflammatory and demyelinating disease of the central nervous system. Hyperphosphorylation and pathological aggregation of microtubule-associated protein tau is a common feature of many neurodegenerative diseases with axonal degeneration including Alzheimer's disease. We have therefore analyzed tau phosphorylation, solubility and distribution in the brainstem of rats with experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Tau was hyperphosphorylated at several sites also phosphorylated in Alzheimer's disease and became partially detergent-insoluble in EAE brains. Morphological examination demonstrated accumulation of amorphous deposits of abnormally phosphorylated tau in the cell body and axons of neurons within demyelinating plaques. Hyperphosphorylation of tau was accompanied by up-regulation of p25, an activator of cyclin-dependent kinase 5. Phosphorylation of tau, activation of cdk5, and axonal pathology were significantly reduced when diseased rats were treated with prednisolone, a standard therapy of acute relapses in MS. Hyperphosphorylation of tau was not observed in a genetic or nutritional model of axonal degeneration or demyelination, suggesting that inflammation as detected in the brains of rats with EAE is the specific trigger of tau pathology. In summary, our data provide evidence that axonal damage in EAE and possibly MS is linked to tau pathology.


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RGD Object Information
RGD ID: 1358431
Created: 2005-06-11
Species: All species
Last Modified: 2005-06-11
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.