Relative efficacies of amyloid beta peptide (A beta) binding proteins in A beta aggregation.
The aggregation of amyloid beta peptide (A beta) into its fibrillar, cross beta-pleated configuration is generally viewed as a critical event in the pathophysiology of Alzheimer's disease (AD). A diverse group of molecules, the A beta binding proteins, has been evaluated for their effects on this process. However, most of these studies have used micromolar or greater reagent concentrations, and their different methods have not permitted quantitative comparisons of the efficacy of different A beta binding proteins in augmenting or inhibiting aggregation. In the present work we have undertaken a coherent analysis using fluorimetry of thioflavin T-stained experimental solutions. The complement protein C1q, serum amyloid P, and transthyretin significantly enhanced the formation of precipitable, cross beta-pleated aggregates in solutions of 800 nM A beta 1-42. Under these same experimental conditions, alpha 1-antichymotrypsin had no significant effect on the aggregation process, and both the E3 and E4 isoforms of apolipoprotein E were significant inhibitors. There was a non-significant trend toward the E3 isoform exhibiting greater inhibition than the E4 isoform. Of the aggregation-facilitating molecules, C1q was substantially and significantly the most potent.
Webster
S
S
L.J. Roberts Center for Alzheimer's Research, Sun Health Research Institute, Arizona 85372, USA.
Rogers
J
J
D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001057:Apolipoproteins E / Q000378:metabolism; D052160:Benzothiazoles; D015922:Complement C1q / Q000378:metabolism; D006801:Humans; D011228:Prealbumin / Q000378:metabolism; D011485:Protein Binding; D000683:Serum Amyloid P-Component / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013844:Thiazoles; D000514:alpha 1-Antichymotrypsin / Q000378:metabolism
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D052160:Benzothiazoles; D011228:Prealbumin; D000683:Serum Amyloid P-Component; D013844:Thiazoles; D000514:alpha 1-Antichymotrypsin; C009462:thioflavin T; D015922:Complement C1q