Aggregation‐Prone Amyloid‐β⋅CuII Species Formed on the Millisecond Timescale under Mildly Acidic Conditions. Issue 9 (18th May 2015)

• Record Type: Journal Article
• Authors: Pedersen, Jeppe T.; Borg, Christian B.; Michaels, Thomas C. T.; Knowles, Tuomas P. J.; Faller, Peter; Teilum, Kaare; Hemmingsen, Lars
• Is Part Of: Chembiochem. Volume 16:Issue 9(2015)
• Page Start: 1293
• Page End: 1297
• Publication Date: 2015-05-18
• Subjects: Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201500080
• Languages: English
• ISSNs: 1439-4227

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>Metal ions and their interaction with the amyloid beta (Aβ) peptide might be key elements in the development of Alzheimer's disease. In this work the effect of Cu^II on the aggregation of Aβ is explored on a timescale from milliseconds to days, both at physiological pH and under mildly acidic conditions, by using stopped‐flow kinetic measurements (fluorescence and light‐scattering), ¹H NMR relaxation and ThT fluorescence. A minimal reaction model that relates the initial Cu^II binding and Aβ folding with downstream aggregation is presented. We demonstrate that a highly aggregation prone Aβ<bold>⋅</bold>Cu^II species is formed on the sub‐second timescale at mildly acidic pH. This observation might be central to the molecular origin of the known detrimental effect of acidosis in Alzheimer's disease.</p> </abstract>