Biophysical characterization of tau amyloid aggregationand the intermediates interaction with biological membranes

MEDINA, L; VERA, C; RAISMAN-VOZARI R,; PAPY-GARCIA D,; CHEHÍN ROSANA.

Congreso; Latin American Crosstalk in Biophysics and Physiology; 2015

Alzheimer's disease (AD) is a neurodegenerative disease histologically characterized by the extracellular accumulation of senile plaques consisting of amyloid-β protein and intracellular amyloid aggregates. These intracellular aggregates appear as paired helical filaments (PHFs) or straight filaments which associate into the higher order structures of neurofibrillary tangles (NFTs). The later are made of abnormally phosphorylated Tau protein and its formation in the central nervous system has been proposed to play a central role in the development and evolution of AD [1]. There are different experimental systems to study the conditions for Tau aggregation in vitro, that can be summarized in a common overall reaction scheme. Here, we use the addition of a polyanionic cofactor such as heparin which increases reaction rates of Tau aggregation. The conformational changes are monitored using different biophysical techniques such as SAXS, IR, fluorescence spectroscopy and fluorescence microscopy [2]. We also study the 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 PHF aggregation and devise methods to prevent it [3]. References: 1. Gordon, P.H., et al., Neurology, 2004. 62(10): p. 1845-7.2. LeVine, H., 3rd, Methods Enzymol, 1999. 309: p. 274-84.3. Barghorn, S. Mandelkow, E., Biochemistry 2002, 41, 14885-14896