Tau Protein Phosphorylated at Threonine-231 is Expressed Abundantly in the Cerebellum in Prion Encephalopathies.

BACKGROUND

Transmissible spongiform encephalopathies (TSEs) are rare neurodegenerative disorders that affect animals and humans. Bovine spongiform encephalopathy (BSE) in cattle, and Creutzfeld-Jakob Disease (CJD) in humans belong to this group. The causative agent of TSEs is called "prion", which corresponds to a pathological form (PrPSc) of a normal cellular protein (PrPC) expressed in nerve cells. PrPSc is resistant to degradation and can induce abnormal folding of PrPC, and TSEs are characterized by extensive spongiosis and gliosis and the presence of PrPSc amyloid plaques. CJD presents initially with clinical symptoms similar to Alzheimer's disease (AD). In AD, tau aggregates and amyloid-β protein plaques are associated with memory loss and cognitive impairment in patients.

OBJECTIVE

In this work, we study the role of tau and its relationship with PrPSc plaques in CJD.

METHODS

Multiple immunostainings with specific antibodies were carried out and analyzed by confocal microscopy.

RESULTS

We found increased expression of the glial fibrillary acidic protein (GFAP) and matrix metalloproteinase (MMP-9), and an exacerbated apoptosis in the granular layer in cases with prion disease. In these cases, tau protein phosphorylated at Thr-231 was overexpressed in the axons and dendrites of Purkinje cells and the extensions of parallel fibers in the cerebellum.

CONCLUSION

We conclude that phosphorylation of tau may be a response to a toxic and inflammatory environment generated by the pathological form of prion.