title: Non-conjugated small molecule FRET for differentiating monomers from higher molecular weight amyloid beta species.
abstract: BACKGROUND
  Systematic differentiation of amyloid (Aβ) species could be important for diagnosis of Alzheimer's disease (AD). In spite of significant progress, controversies remain regarding which species are the primary contributors to the AD pathology, and which species could be used as the best biomarkers for its diagnosis. These controversies are partially caused by the lack of reliable methods to differentiate the complicated subtypes of Aβ species. Particularly, differentiation of Aβ monomers from toxic higher molecular weight species (HrMW) would be beneficial for drug screening, diagnosis, and molecular mechanism studies. However, fast and cheap methods for these specific aims are still lacking.
  
  
  RESULTS
  We demonstrated the feasibility of a non-conjugated FRET (Förster resonance energy transfer) technique that utilized amyloid beta (Aβ) species as intrinsic platforms for the FRET pair assembly. Mixing two structurally similar curcumin derivatives that served as the small molecule FRET pair with Aβ40 aggregates resulted in a FRET signal, while no signal was detected when using Aβ40 monomer solution. Lastly, this FRET technique enabled us to quantify the concentrations of Aβ monomers and high molecular weight species in solution.
  
  
  CONCLUSIONS
  We believe that this FRET technique could potentially be used as a tool for screening for inhibitors of Aβ aggregation. We also suggest that this concept could be generalized to other misfolded proteins/peptides implicated in various pathologies including amyloid in diabetes, prion in bovine spongiform encephalopathy, tau protein in AD, and α-synuclein in Parkinson disease.
authors.affiliation: Molecular Imaging Laboratory, Department of Radiology, MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital/Harvard Medical School, Charlestown, Massachusetts, United States of America.
authors.forename: Chongzhao
authors.initials: C
authors.lastname: Ran
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.forename: Robert D
authors.initials: RD
authors.lastname: Moir
authors.forename: Anna
authors.initials: A
authors.lastname: Moore
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000302:isolation & purification; D001671:Biochemistry / Q000379:methods; D003474:Curcumin / Q000737:chemistry; D019281:Dimerization; D031541:Fluorescence Resonance Energy Transfer / Q000379:methods*; D006801:Humans; D008970:Molecular Weight; D010446:Peptide Fragments / Q000737:chemistry; D011485:Protein Binding; D011489:Protein Denaturation; D017510:Protein Folding
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D003474:Curcumin