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X‐Ray Diffraction Analysis of Brain Lipid Membrane Structure in Alzheimer's Disease and β‐Amyloid Peptide Interactions a
Author(s) -
MASON R. PRESTON,
SHAJENKO LYDIA,
HERBETTE LEO G.
Publication year - 1993
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1993.tb23027.x
Subject(s) - phospholipid , chemistry , lipid bilayer , cholesterol , membrane , membrane structure , membrane protein , membrane fluidity , biophysics , bilayer , peptide , biochemistry , endocrinology , biology
Small angle x‐ray diffraction analysis of Alzheimer's disease (AD) lipid membranes reconstituted from cortical gray matter showed significant, reproducible structure changes relative to age‐matched control samples. 1 Specifically, there was an average 4 Å reduction in the lipid bilayer width and marked changes in membrane electron density profiles of AD cortical samples. There were no significant structure differences in the membrane bilayers isolated from an unaffected region (cerebellum) of the AD brain. Lipid and protein analysis of six AD and six age‐matched controls showed that the phospholipid : protein mass ratio was unchanged, but that the unesterified chlolesterol : phospholipid (C : PL) mole ratio decreased by 30% in the AD temporal gyrus relative to age‐matched controls. The C : PL mole ratio was not significantly different for samples prepared from cerebellum of AD versus control patients. X‐ray diffraction analysis of a cholesterol‐enriched AD sample demonstrated a virtual restoration of the normal membrane bilayer width and electron density profile, suggesting that the cholesterol deficit played a major role in the AD lipid membrane structure perturbation. Addition of β‐amyloid peptide to bovine brain phospholipid membranes signficantly changed the electron density associated with the hydrocarbon core. Alterations in the composition and structure of the membrane bilayer may play an important role in the pathophysiology of AD by altering the activity and catabolism of membrane‐bound proteins, including the β‐amyloid precursor protein.