Structural typing of systemic amyloidoses by luminescent-conjugated polymer spectroscopy.
Most systemic amyloidoses are progressive and lethal, and their therapy depends on the identification of the offending proteins. Here we report that luminescent-conjugated thiophene polymers (LCP) sensitively detect amyloid deposits. The heterodisperse polythiophene acetic acid derivatives, polythiophene acetic acid (PTAA) and trimeric PTAA, emitted yellow-red fluorescence on binding to amyloid deposits, whereas chemically homogeneous pentameric formic thiophene acetic acid emitted green-yellow fluorescence. The geometry of LCPs modulates the spectral composition of the emitted light, thereby reporting ligand-induced steric changes. Accordingly, a screen of PTAA-stained amyloid deposits in histological tissue arrays revealed striking spectral differences between specimens. Blinded cluster assignments of spectral profiles of tissue samples from 108 tissue samples derived from 96 patients identified three nonoverlapping classes, which were found to match AA, AL, and ATTR immunotyping. We conclude that LCP spectroscopy is a sensitive and powerful tool for identifying and characterizing amyloid deposits.
Nilsson
K Peter R
KP
Institute of Neuropathology, Department of Pathology, University Hospital of Zurich,CH-8091 Zurich, Switzerland.
Ikenberg
Kristian
K
Aslund
Andreas
A
Fransson
Sophia
S
Konradsson
Peter
P
Röcken
Christoph
C
Moch
Holger
H
Aguzzi
Adriano
A
D019342:Acetic Acid / Q000737:chemistry; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000682:Amyloid / Q000737:chemistry* / Q000145:classification* / Q000378:metabolism; D000686:Amyloidosis / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D049408:Luminescent Agents / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D015394:Molecular Structure; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D013050:Spectrometry, Fluorescence / Q000379:methods; D013194:Staining and Labeling / Q000379:methods; D013876:Thiophenes / Q000737:chemistry / Q000494:pharmacology; D055815:Young Adult
D000682:Amyloid; D049408:Luminescent Agents; D011108:Polymers; D013876:Thiophenes; C066730:polythiophene; D019342:Acetic Acid