title: The relationship between truncation and phosphorylation at the C-terminus of tau protein in the paired helical filaments of Alzheimer's disease.
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.
authors.affiliation: Departments of Physiology, Biophysics, and Neurosciences, Centro de Investigación y de Estudios Avanzados del IPN (Instituto Politecnico Nacional) Gustavo A. Madero, Mexico.
authors.forename: Paola
authors.initials: P
authors.lastname: Flores-Rodríguez
authors.affiliation: Departments of Cell Biology, Centro de Investigación y de Estudios Avanzados del IPN (Instituto Politecnico Nacional) Gustavo A. Madero, Mexico.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Ontiveros-Torres
authors.affiliation: Departments of Molecular Biomedicine, Centro de Investigación y de Estudios Avanzados del IPN (Instituto Politecnico Nacional) Gustavo A. Madero, Mexico.
authors.forename: María C
authors.initials: MC
authors.lastname: Cárdenas-Aguayo
authors.affiliation: Departments of Cell Biology, Centro de Investigación y de Estudios Avanzados del IPN (Instituto Politecnico Nacional) Gustavo A. Madero, Mexico.
authors.forename: Juan P
authors.initials: JP
authors.lastname: Luna-Arias
authors.affiliation: Departments of Molecular Biomedicine, Centro de Investigación y de Estudios Avanzados del IPN (Instituto Politecnico Nacional) Gustavo A. Madero, Mexico.
authors.forename: Marco A
authors.initials: MA
authors.lastname: Meraz-Ríos
authors.affiliation: Brain Bank-Laboratorio Nacional de Servicios Experimentales, Department of National Laboratories of Experimental Services, Centro de Investigación y de Estudios Avanzados del Instituto Politecnico Nacional Gustavo A. Madero, Mexico.
authors.forename: Amparo
authors.initials: A
authors.lastname: Viramontes-Pintos
authors.affiliation: School of Medicine and Dentistry, University of Aberdeen Aberdeen, UK.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Harrington
authors.affiliation: School of Medicine and Dentistry, University of Aberdeen Aberdeen, UK.
authors.forename: Claude M
authors.initials: CM
authors.lastname: Wischik
authors.affiliation: Departments of Physiology, Biophysics, and Neurosciences, Centro de Investigación y de Estudios Avanzados del IPN (Instituto Politecnico Nacional) Gustavo A. Madero, Mexico.
authors.forename: Raúl
authors.initials: R
authors.lastname: Mena
authors.affiliation: Departments of Physiology, Biophysics, and Neurosciences, Centro de Investigación y de Estudios Avanzados del IPN (Instituto Politecnico Nacional) Gustavo A. Madero, Mexico.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Florán-Garduño
authors.affiliation: Brain Bank-Laboratorio Nacional de Servicios Experimentales, Department of National Laboratories of Experimental Services, Centro de Investigación y de Estudios Avanzados del Instituto Politecnico Nacional Gustavo A. Madero, Mexico.
authors.forename: José
authors.initials: J
authors.lastname: Luna-Muñoz
keywords: Alzheimer's disease; PHFs; neurofibrillary tangles; neurotoxicity; tau oligomers; tau protein; truncation