Peptide probe for rapid and specific detection of amyloid aggregation

Abstract

A method for use of a peptide probe that generates fluorescence signals rapidly upon recognition of various Aβ aggregates without significant perturbation of samples. The present peptide probes display an increase in fluorescence signals upon coincubation with Aβ oligomers, but neither monomeric / dimeric species nor fibrils. The detection can occur within an hour or two without any additional sample preparation and incubation steps.

Description

STATEMENT OF RELATED APPLICATIONS[0001]This application is a division of U.S. patent application Ser. No. 12 / 856,209 having a filing date of 13 Aug. 2012, which is based on and claims the benefit of U.S. Provisional Patent Application No. 61 / 234,083 having a filing date of 14 Aug. 2010, currently pending, both of which are incorporated herein in their entireties by this reference.SEQUENCE LISTING[0002]The instant application contains a Sequence Listing that has been submitted in ASCII format via EFS-Web and is hereby incorporated by reference in its entirety. Said ASCII copy, created on 16 Sep. 2011, is named 484673US.txt and is 2,831 bytes in size.BACKGROUND OF THE INVENTION[0003]1. Technical Field[0004]This invention is generally related to the field of peptide probes, to the field of peptide probes for the detection of amyloid aggregation, and to the field of peptide probes for the rapid and specific detection of amyloid aggregation.[0005]2. Prior Art[0006]Aggregation of a 39-43 ...

AI Technical Summary

Problems solved by technology

However, the possibility that the Aβ fibrils may be associated with neurotoxicity cannot be ruled out, since fibrillar aggregates can serve as a pool of soluble intermediate species through a dynamic exchange with monomers or oligomers (Id.

However, the complex nature of Aβ aggregation, including the generation of transient aggregate intermediates, impedes the establishment of a functional correlation between Aβ aggregation characteristics and their cellular / clinical manifestations.

Inaccurate quantification of various aggregate species would result in the gap seen between basic scientific discovery and cellular / clinical manifestations, and the discrepancy among observations from animal model studies.

The currently available compounds or methods, however, either do not distinguish different aggregate species or are inappropriate for rapid, non-perturbative detection due to the requirement of additional sample preparation and incubation steps (Kayed, R., et al., Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis, Science 300, 486-489, 2003; Williams, A. D., et al., Structural properties of Abeta protofibrils stabilized by a small molecule, Proc Natl Acad Sci USA 102, 7115-7120, 2005; Kayed, R., et al., Conformation-dependent anti-amyloid oligomer antibodies, Methods Enzymol 413, 326-344, 2006; Kayed, R., et al., Fibril specific, conformation dependent antibodies recognize a generic epitope common to amyloid fibrils and fibrillar oligomers that is absent in prefibrillar oligomers, Mol Neurodegener 2, 18, 2007; Linke, R. P., et al., High-sensitivity diagnosis of AA amyloidosis using Congo red and immunohistochemistry detects missed amyloid deposits, J Histochem Cytochem 43, 863-869, 1995; LeVine, H., 3rd, Quantification of beta-sheet amyloid fibril structures with thioflavin T, Methods Enzymol 309, 274-284, 1999).

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