title: A universal method for detection of amyloidogenic misfolded proteins.
abstract: Diseases associated with the misfolding of endogenous proteins, such as Alzheimer's disease and type II diabetes, are becoming increasingly prevalent. The pathophysiology of these diseases is not totally understood, but mounting evidence suggests that the misfolded protein aggregates themselves may be toxic to cells and serve as key mediators of cell death. As such, an assay that can detect aggregates in a sensitive and selective fashion could provide the basis for early detection of disease, before cellular damage occurs. Here we report the evolution of a reagent that can selectively capture diverse misfolded proteins by interacting with a common supramolecular feature of protein aggregates. By coupling this enrichment tool with protein specific immunoassays, diverse misfolded proteins and sub-femtomole amounts of oligomeric aggregates can be detected in complex biological matrices. We anticipate that this near-universal approach for quantitative misfolded protein detection will become a useful research tool for better understanding amyloidogenic protein pathology as well as serve as the basis for early detection of misfolded protein diseases.
authors.affiliation: Novartis Vaccines and Diagnostics, Inc., 4560 Horton St., Emeryville, CA 94608, USA.
authors.forename: Alice Y
authors.initials: AY
authors.lastname: Yam
authors.forename: Xuemei
authors.initials: X
authors.lastname: Wang
authors.forename: Carol Man
authors.initials: CM
authors.lastname: Gao
authors.forename: Michael D
authors.initials: MD
authors.lastname: Connolly
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Zuckermann
authors.forename: Thieu
authors.initials: T
authors.lastname: Bleu
authors.forename: John
authors.initials: J
authors.lastname: Hall
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Fedynyshyn
authors.forename: Sophie
authors.initials: S
authors.lastname: Allauzen
authors.forename: David
authors.initials: D
authors.lastname: Peretz
authors.forename: Cleo M
authors.initials: CM
authors.lastname: Salisbury
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism; D042241:Early Diagnosis; D006801:Humans; D007202:Indicators and Reagents / Q000737:chemistry / Q000378:metabolism; D008970:Molecular Weight; D034444:Peptoids / Q000737:chemistry / Q000378:metabolism; D017510:Protein Folding; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D057165:Proteostasis Deficiencies / Q000175:diagnosis*
chemical_list: D000682:Amyloid; D007202:Indicators and Reagents; D034444:Peptoids