AUTHOR=Flores-Rodríguez Paola , Ontiveros-Torres Miguel A. , Cárdenas-Aguayo María C. , Luna-Arias Juan P. , Meraz-Ríos Marco A. , Viramontes-Pintos Amparo , Harrington Charles R. , Wischik Claude M. , Mena Raúl , Florán-Garduño Benjamin , Luna-Muñoz José TITLE=The relationship between truncation and phosphorylation at the C-terminus of tau protein in the paired helical filaments of Alzheimer's disease JOURNAL=Frontiers in Neuroscience VOLUME=9 YEAR=2015 URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2015.00033 DOI=10.3389/fnins.2015.00033 ISSN=1662-453X ABSTRACT=

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.