Interactions of Abeta(1-40) with glycerophosphocholine and intact erythrocyte membranes: fluorescence and circular dichroism studies.
Deposition of amyloid beta peptide in human brain in the form of senile plaques is a neuropathological hallmark of Alzheimer's disease (AD). Levels of a phospholipid breakdown product, glycerophosphocholine (GPC), also increase in AD brain. The effect of GPC on amyloid beta(1-40) peptide (Abeta) aggregation in PBS buffer was investigated by circular dichroism and fluoresence spectroscopy; interactions of Abeta and GPC with the intact erythrocyte membrane was examined by fluoresence spectroscopy. Fluorescamine labeled Abeta studies indicate GPC enhances Abeta aggregation. CD spectroscopy reveals that Abeta in the presence of GPC adopts 14% more beta-sheet structure than does Abeta alone. Fluorescamine anisotropy measurements show that GPC and Abeta interact in the phospholipid head-group region of the erythrocyte membrane. In summary, both soluble Abeta and GPC insert into the phospholipid head-group region of the membrane where they interact leading to beta-sheet formation in soluble Abeta which enhances Abeta aggregation.
Mandal
Pravat K
PK
Neurophysics Laboratory, Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA.
McClure
Richard J
RJ
Pettegrew
Jay W
JW
D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D016880:Anisotropy; D002942:Circular Dichroism; D004910:Erythrocyte Membrane / Q000737:chemistry*; D005450:Fluorescamine / Q000737:chemistry; D006801:Humans; D007202:Indicators and Reagents; D010446:Peptide Fragments / Q000737:chemistry*; D010715:Phosphatidylglycerols / Q000737:chemistry*; D017433:Protein Structure, Secondary; D013050:Spectrometry, Fluorescence
D016229:Amyloid beta-Peptides; D007202:Indicators and Reagents; D010446:Peptide Fragments; D010715:Phosphatidylglycerols; C078592:amyloid beta-protein (1-40); D005450:Fluorescamine