Amyloid-β protofibrils differ from amyloid-β aggregates induced in dilute hexafluoroisopropanol in stability and morphology

Michael R. Nichols, Melissa A. Moss, Dana Kim Reed, Stephanie Cratic-McDaniel, Jan H. Hoh, Terrone L. Rosenberry

Research output: Contribution to journalArticle


The brains of Alzheimer's disease (AD) patients contain large numbers of amyloid plaques that are rich in fibrils composed of 40- and 42-residue amyloid-β (Aβ) peptides. Several lines of evidence indicate that fibrillar Aβ and especially soluble Aβ aggregates are important in the etiology of AD. Recent reports also stress that amyloid aggregates are polymorphic and that a single polypeptide can fold into multiple amyloid conformations. Here we demonstrate that Aβ-(1-40) can form soluble aggregates with predominant β-structures that differ in stability and morphology. One class of aggregates involved soluble Aβ protofibrils, prepared by vigorous overnight agitation of monomeric Aβ-(1-40) at low ionic strength. Dilution of these aggregation reactions induced disaggregation to monomers as measured by size exclusion chromatography. Protofibril concentrations monitored by thioflavin T fluorescence decreased in at least two kinetic phases, with initial disaggregation (rate constant ∼1 h -1) followed by a much slower secondary phase. Incubation of the reactions without agitation resulted in less disaggregation at slower rates, indicating that the protofibrils became progressively more stable over time. In fact, protofibrils isolated by size exclusion chromatography were completely stable and gave no disaggregation. A second class of soluble Aβ aggregates was generated rapidly (

Original languageEnglish (US)
Pages (from-to)2471-2480
Number of pages10
JournalJournal of Biological Chemistry
Issue number4
StatePublished - Jan 28 2005


ASJC Scopus subject areas

  • Biochemistry

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