Biophysical characterization of tau amyloid aggregation and the intermediates interaction with biological membranes

MEDINA, LUCIANA; VERA, CECILIA; RAISMAN-VOZARI, RITA; PAPY-GARCIA, DULCE

Encuentro; VIII PosLatAm course: Membrane Lipids, Transporters, Channels and all that crosstalk; 2015

Alzheimer´s disease (AD) is a neurodegenerative disease histologicallycharacterized by the extracellular accumulation of senile plaques consistingof amyloid-β protein and intracellular amyloid aggregates. Theseintracellular aggregates appear as paired helical filaments (PHFs) or straightfilaments which associate into the higher order structures of neurofibrillarytangles (NFTs). The later are made of abnormally phosphorylated Tauprotein and its formation in the central nervous system has been proposed toplay a central role in the development and evolution of AD [1]. There aredifferent experimental systems to study the conditions for Tau aggregationin vitro, that can be summarized in a common overall reaction scheme.Here, we use the addition of a polyanionic cofactor such as heparin whichincreases reaction rates of Tau aggregation. The conformational changes aremonitored using different biophysical techniques such as SAXS, IR,fluorescence spectroscopy and fluorescence microscopy [2]. We also studythe interaction of Tau aggregation intermediates with phospholipid vesicles,in order to analyze their ability to alter membrane stability.A unified view of PHF aggregation helps to analyze the causes of PHFaggregation and devise methods to prevent it [3].