Tau Aggregation Followed by Atomic Force Microscopy and Surface Plasmon Resonance, and Single Molecule Tau-Tau Interaction Probed by Atomic Force Spectroscopy

Article type: Research Article

Authors: Barrantes, Alejandro^{a; b;} | Sotres, Javier^c; | Hernando-Pérez, Mercedes^d | Benítez, Maria J.^{a; b} | de Pablo, Pedro J.^d | Baró, Arturo M.^c | Ávila, Jesus^a | Jiménez, Juan S.^{a; b; *}

Affiliations: [a] Centro de Biología Molecular Severo Ochoa, CSIC, Madrid, Spain | [b] Departamento de Química Física Aplicada, Universidad Autónoma de Madrid, Madrid, Spain | [c] Instituto de Ciencia de Materiales de Madrid, CSIC, Madrid, Spain | [d] Departamento de Física de la Materia Condensada, Universidad Autónoma de Madrid, Madrid, Spain

Correspondence: [*] Corresponding author: Juan S. Jiménez, Depto Química Física Aplicada, Facultad de Ciencias, Universidad Autónoma de Madrid, Canto Blanco 28049, Madrid, Spain. Tel.: +34 914974724; Fax: +34 914974785; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: Intracellular neurofibrillary tangles, composed mainly of tau protein, and extracellular plaques, containing mostly amyloid-β, are the two types of protein aggregates found upon autopsy within the brain of Alzheimer's disease patients. Polymers of tau protein can also be found in other neurodegenerative disorders known as tauopathies. Tau is a highly soluble protein, intrinsically devoid of secondary or tertiary structure, as many others proteins particularly prone to form fibrillar aggregations. The mechanism by which this unfolded molecule evolves to the well ordered helical filaments has been amply studied. In fact, it is a very slow process when followed in the absence of aggregation inducers. Herein we describe the use of surface plasmon resonance, atomic force microscopy, and atomic force spectroscopy to detect tau-tau interactions and to follow the process of aggregation in the absence of aggregation inducers. Tau-tau interactions are clearly detected, although a very long period of time is needed to observe filaments formation. Tau oligomers showing a granular appearance, however, are observed immediately as a consequence of this interaction. These granular tau oligomers slowly evolve to larger structures and eventually to filaments having a size smaller than those reported for paired helical filaments purified from Alzheimer's disease.

Keywords: Alzheimer's disease, neurodegeneration, tau protein aggregation and interaction

DOI: 10.3233/JAD-2009-1130

Journal: Journal of Alzheimer's Disease, vol. 18, no. 1, pp. 141-151, 2009