The relationship between truncation and phosphorylation at the C-terminus of tau protein in the paired helical filaments of Alzheimer's disease.

• Main Authors: Paola eFlores-Rodríguez, Miguel Angel eOntiveros-Torres, María del Carmen eCárdenas-Aguayo, Juan Pedro eLuna-Arias, MARCO ANTONIO eMERAZ-RÍOS, Amparo eViramontes-Pintos, Charles eHarrington, Claude eM. Wischik, Benjamín eFlorán, Raúl eMena, José eLuna-Muñoz
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2015-02-01
• Series: Frontiers in Neuroscience
• Subjects: Alzheimer Disease; Neurofibrillary Tangles; Neurotoxicity; tau protein; Tau oligomers; Truncation
• Online Access: http://journal.frontiersin.org/Journal/10.3389/fnins.2015.00033/full
• ISSN: 1662-453X

We previously demonstrated that, in the early stages of tau processing in Alzheimer’s disease, the N-terminal part of the molecule undergoes a characteristic cascade of phosphorylation and progressive misfolding of the proteins resulting in a structural conformation detected by Alz-50. In this immunohistochemical study of AD brain tissue, we have found that C-terminal truncation of tau at Asp-421 was an early event in tau aggregation and analyzed the relationship between phospho-dependent tau epitopes located at the C-terminus with truncation at Glu-391. The aim of this study was to determine whether C-terminal truncation may trigger events leading to the assembly of insoluble PHFs from soluble tau aggregates present in pre-tangle cells. Our findings suggest that there is a complex interaction between phosphorylated and truncated tau species. A model is presented here in which truncated tau protein represents an early neurotoxic species while phosphorylated tau species may provide a neuroprotective role in Alzheimer’s disease.