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Relative efficacies of amyloid β peptide (Aβ) binding proteins in Aβ aggregation
Author(s) -
Webster Scott,
Rogers Joseph
Publication year - 1996
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19961001)46:1<58::aid-jnr8>3.0.co;2-e
Subject(s) - thioflavin , chemistry , peptide , transthyretin , protein aggregation , gene isoform , amyloid (mycology) , biophysics , biochemistry , alzheimer's disease , biology , medicine , disease , endocrinology , inorganic chemistry , gene
The aggregation of amyloid β peptide (Aβ) into its fibrillar, cross β‐pleated configuration is generally viewed as a critical event in the pathophysiology of Alzheimer's disease (AD). A diverse group of molecules, the Aβ 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 Aβ 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 β‐pleated aggregates in solutions of 800 nM Aβ1–42. Under these same experimental conditions, α 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. © 1996 Wiley‐Liss, Inc.