non-conjugated small molecule fret for differentiating monomers from higher molecular weight amyloid beta speciesnon-conjugated区分单体小分子担心从高分子量β淀粉样蛋白的物种.pdfVIP

Non-Conjugated Small Molecule FRET for Differentiating Monomers from Higher Molecular Weight Amyloid Beta Species 1 1 2 1 Chongzhao Ran , Wei Zhao , Robert D. Moir , Anna Moore * 1 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, 2 Alzheimer’s Disease Research Unit, Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts, United States of America Abstract Background: Systematic differentiation of amyloid (Ab) 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 Ab species. Particularly, differentiation of Ab 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. ¨ Principal Findings: We demonstrated the feasibility of a non-conjugated FRET (Forster resonance energy transfer) technique that utilized amyloid beta (Ab) species as intrinsic platforms for the FRET pair assembly. Mixing two structurally similar curcumin derivatives that served as the small molecule FRET pair with Ab40 aggregates resulted in a FRET signal, while no sig