Tau aggregation followed by atomic force microscopy and surface plasmon resonance, and single molecule tau-tau interaction probed by atomic force spectroscopy.
Intracellular neurofibrillary tangles, composed mainly of tau protein, and extracellular plaques, containing mostly amyloid-beta, 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.
Barrantes
Alejandro
A
Centro de Biología Molecular Severo Ochoa, CSIC, Madrid, Spain.
Sotres
Javier
J
Hernando-Pérez
Mercedes
M
Benítez
Maria J
MJ
de Pablo
Pedro J
PJ
Baró
Arturo M
AM
Avila
Jesus
J
Jiménez
Juan S
JS
D000544:Alzheimer Disease / Q000378:metabolism; D002449:Cell Aggregation / Q000502:physiology; D006801:Humans; D018625:Microscopy, Atomic Force / Q000379:methods; D017510:Protein Folding; D054730:Protein Interaction Domains and Motifs / Q000502:physiology*; D020349:Surface Plasmon Resonance / Q000379:methods; D016875:tau Proteins / Q000737:chemistry / Q000378:metabolism*
D016875:tau Proteins