Pathological-Like Assembly of tau Induced by a Paired Helical Filament Core Expressed at the Plasma Membrane

• Published in: Journal of Alzheimer's disease Vol. 18; no. 4; pp. 919 - 933
• Main Authors: Campos-Peña, Victoria, Tapia-Ramírez, José, Sánchez-Torres, Carmen, Meraz-Rios, Marco Antonio
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.01.2009
• Subjects: Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Animals; Cell Membrane - metabolism; Cell Membrane - pathology; Cercopithecus aethiops; COS Cells; Gene Expression; Humans; Hydrogen Peroxide - metabolism; Neurofibrillary Tangles - pathology; Neurofibrillary Tangles - ultrastructure; Oxidative Stress; Phosphorylation; tau Proteins - metabolism; tau Proteins - ultrastructure; β-pleated sheet; paired helical filaments; Alzheimer's disease; membrane localization; tau aggregation
• ISSN: 1387-2877; 1875-8908
• DOI: 10.3233/JAD-2009-1198

The hallmark of Alzheimer's disease is the pathological aggregation of tau proteins into paired helical filaments and neurofibrillary tangles. This paper evaluates the abnormal expression and localization of chimeric tau molecules at the plasma membrane of COS-7 cells and its relationship with tau polymerization. Overexpression of these proteins, in combination with either tau441 or tau391, induces tau to assemble into β-pleated sheets that are recognized by Thiazin red. Immunoelectromicroscopy analysis revealed the presence of filaments close to the plasma membrane resembling those found in Alzheimer's disease. The capacity of plasma membrane-associated chimeric tau proteins to capture full length tau was increased in the presence of H2O2 or okadaic acid treatments. This suggests that hyperphosphorylation or an oxidative environment could both influence the biochemical properties of the cell that lead to assembly of paired helical filaments. The altered localization of tau protein at the plasma membrane could play a key role in the assembly of pathological tau.