title: Effect of Ca(2+) on Aß40 fibrillation is characteristically different.
abstract: Alzheimer's disease (AD) is the only one among top ten diseases in USA that cannot be cured, prevented or slowed down. At molecular level the mechanism of onset has been closely associated with mis-folding of Aβ40 and Aβ42 and is well supported by the genetic data for AD. Extensive research efforts have led to identification of factors and metal ions that could manipulate Aβ equilibrium, especially Ca(2+). Previously, we reported selectively acceleration of Aβ42 fibril formation by Ca(2+)in vitro within physiological concentrations (BBA (2009) 1794:1536). Aβ40 on the other hand did not appear to be significantly affected by Ca(2+) addition. In an effort to understand the distinctive behavior of Aβ40, we monitored changes of Aβ40 aggregation by intrinsic tyrosine fluorescence and CD and took different approaches for data processing. Our analysis of CD data indicates a complex effect induced by the addition of 2mM Ca(2+) resulting in an increase in the rate of transformation from monomer to β-sheet rich fibrilar or intermediate species formation in Aβ40. Surprisingly, the kinetics observed by intrinsic fluorescence studies in this article and ThT, SEC or EM studies in our previous report were not able to unravel the existence of this effect in Aβ40.
authors.affiliation: Department of Biology, East Carolina University, Greenville, NC 27858, United States. Electronic address: ahmada@ecu.edu.
authors.forename: Atta
authors.initials: A
authors.lastname: Ahmad
authors.affiliation: Department of Biology, East Carolina University, Greenville, NC 27858, United States.
authors.forename: Caleb M
authors.initials: CM
authors.lastname: Stratton
authors.affiliation: Department of Biology, East Carolina University, Greenville, NC 27858, United States.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Scemama
authors.affiliation: Department of Biology, East Carolina University, Greenville, NC 27858, United States.
authors.forename: Mahvish
authors.initials: M
authors.lastname: Muzaffar
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry*; D002118:Calcium / Q000737:chemistry*; D002413:Cations, Divalent; D002942:Circular Dichroism; D006801:Humans; D010446:Peptide Fragments / Q000737:chemistry*; D066329:Protein Aggregates; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012996:Solutions; D013050:Spectrometry, Fluorescence; D014443:Tyrosine / Q000737:chemistry*
chemical_list: D016229:Amyloid beta-Peptides; D002413:Cations, Divalent; D010446:Peptide Fragments; D066329:Protein Aggregates; D012996:Solutions; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D014443:Tyrosine; D002118:Calcium
keywords: Amyloid; Aβ40; Aβ42; CD; Ca(2+)