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P4–046: Aβ(1–28) amyloid formation depends on membrane lipid composition
Author(s) -
Cortijo-Arellano Marta,
Buzón Victor,
Benseny Núria,
Cócera Mercè,
Cladera Josep
Publication year - 2006
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2006.05.1784
Subject(s) - peptide , chemistry , membrane , fibril , biophysics , liposome , neurodegeneration , p3 peptide , amyloid (mycology) , phospholipid , lipid raft , biochemistry , amyloid precursor protein , alzheimer's disease , biology , pathology , medicine , inorganic chemistry , disease
Background: Alzheimer’s disease is a brain pathology characterized by memory loss and impairment of cognitive functions (speech and motor skills). A major pathological feature is extracellular amyloid plaques in the grey matter. These plaques are formed by fibrils in which the main component is the so called -amyloid peptide (1). This peptide is derived from the amyloid precursor protein (APP) by proteolytic cleavage that appears to occur preferentially in cholesterol-rich lipid rafts. In this way, extensive evidence for lipid membrane being an important factor in neurodegeneration and for the fact that it may influence the formation of fibrils exists in the literature (2). Recently a specific region has been described in the -amyloid peptide as a sphingolipid-binding motif (3). The aggregation capacity of amyloid peptides depends on a conformational change which implies the conversion of -helical structures into -structures. This change is accepted to trigger the aggregation process, with sygmoidal kinetics, usually interpreted as describing a nucleation dependent polymerization. Objective(s): To study the influence of biological membranes on the aggregation of the Alzheimer’s peptide fragment A (1-28). Methods: A (1-28) has been studied using Fourier Transform Infrared Spectroscopy. Formation of -aggregates was monitored by measuring the intensity of specific aggregation band around 1620 cm. Experimental data were fitted to an exponential function in order to obtain the aparent kinetic constant. The A (1-28) peptide was studied in the presence of model membranes (liposomes). Results: Our results suggest that the presence of cholesterol, sphingosine or galactosylceramide in model membranes (liposomes) favors the conversion of -helical structures into -amyloid aggregates at neutral pH. Conclusions: “Raft” lipid components, such as sphingomyelin, cholesterol or galactosylceramide, induce aggregation of the Alzheimer’s peptide fragment A (1-28).