Amyloid-β aggregates formed at polar-nonpolar interfaces differ from amyloid-β protofibrils produced in aqueous buffers

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

Research output: Contribution to journalArticle

Abstract

The deposition of aggregated amyloid-β (Aβ) peptides in the brain as senile plaques is a pathological hallmark of Alzheimer's disease (AD). Several lines of evidence indicate that fibrillar and, in particular, soluble aggregates of these 40- and 42-residue peptides are important in the etiology of AD. Recent studies also stress that amyloid aggregates are polymorphic and that a single polypeptide can fold into multiple amyloid conformations. Here we review our recent reports that Aβ(1-40) in vitro 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) in low ionic strength buffers. These aggregates were quite stable and disaggregated to only a limited extent on dilution. A second class of soluble Aβ aggregates was generated at polar-nonpolar interfaces. Aggregation in a two-phase system of buffer over chloroform occurred more rapidly than in buffer alone. In buffered 2% hexafluoroisopropanol (HFIP), microdroplets of HFIP were formed and the half-time for aggregation was less than 10 minutes. Like Aβ protofibrils, these interfacial aggregates showed increased thioflavin T fluorescence and were rich in β-structure by circular dichroism. However, electron microscopy and atomic force microscopy revealed very different morphologies. The HFIP aggregates formed initial globular clusters that progressed over several days to soluble fibrous aggregates. When diluted out of HFIP these aggregates initially were very unstable and disaggregated completely within 2 minutes. However, their stability increased as they progressed to fibers. It is important to determine whether similar interfacial Aβ aggregates are produced in vivo.

Original languageEnglish (US)
Pages (from-to)164-174
Number of pages11
JournalMicroscopy Research and Technique
Volume67
Issue number3-4
DOIs
StatePublished - Jul 2005

Fingerprint

protein aggregates
amyloid
Amyloid
Buffers
buffers
Peptides
Alzheimer Disease
water
Atomic Force Microscopy
Amyloid Plaques
Chloroform
Circular Dichroism
Osmolar Concentration
Electron Microscopy
Alzheimer disease
Fluorescence
peptides
hexafluoroisopropanol
Agglomeration
Brain

Keywords

  • Alzheimer's disease
  • Fibrils
  • Hexafluoroisopropanol
  • Peptide β-structure
  • Stability

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Anatomy
  • Instrumentation

Cite this

Amyloid-β aggregates formed at polar-nonpolar interfaces differ from amyloid-β protofibrils produced in aqueous buffers. / Nichols, Michael R.; Moss, Melissa A.; Reed, Dana Kim; Hoh, Jan H.; Rosenberry, Terrone L.

In: Microscopy Research and Technique, Vol. 67, No. 3-4, 07.2005, p. 164-174.

Research output: Contribution to journalArticle

Nichols, Michael R. ; Moss, Melissa A. ; Reed, Dana Kim ; Hoh, Jan H. ; Rosenberry, Terrone L. / Amyloid-β aggregates formed at polar-nonpolar interfaces differ from amyloid-β protofibrils produced in aqueous buffers. In: Microscopy Research and Technique. 2005 ; Vol. 67, No. 3-4. pp. 164-174.
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