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

Abstract

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 (PrP ^Sc) of a normal cellular protein (PrP ^C) expressed in nerve cells. PrP ^Sc is resistant to degradation and can induce abnormal folding of PrP ^C, and TSEs are characterized by extensive spongiosis and gliosis and the presence of PrP ^Sc 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 PrP ^Sc 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.