title: In situ characterization of protein aggregates in human tissues affected by light chain amyloidosis: a FTIR microspectroscopy study.
abstract: Light chain (AL) amyloidosis, caused by deposition of amyloidogenic immunoglobulin light chains (LCs), is the most common systemic form in industrialized countries. Still open questions, and premises for developing targeted therapies, concern the mechanisms of amyloid formation in vivo and the bases of organ targeting and dysfunction. Investigating amyloid material in its natural environment is crucial to obtain new insights on the molecular features of fibrillar deposits at individual level. To this aim, we used Fourier transform infrared (FTIR) microspectroscopy for studying in situ unfixed tissues (heart and subcutaneous abdominal fat) from patients affected by AL amyloidosis. We compared the infrared response of affected tissues with that of ex vivo and in vitro fibrils obtained from the pathogenic LC derived from one patient, as well as with that of non amyloid-affected tissues. We demonstrated that the IR marker band of intermolecular β-sheets, typical of protein aggregates, can be detected in situ in LC amyloid-affected tissues, and that FTIR microspectroscopy allows exploring the inter- and intra-sample heterogeneity. We extended the infrared analysis to the characterization of other biomolecules embedded within the amyloid deposits, finding an IR pattern that discloses a possible role of lipids, collagen and glycosaminoglycans in amyloid deposition in vivo.
authors.affiliation: Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy.|Department of Physics, University of Milano-Bicocca, Piazza della Scienza 3, 20126 Milano, Italy.
authors.forename: Diletta
authors.initials: D
authors.lastname: Ami
authors.affiliation: Amyloidosis Research and Treatment Center, Foundation IRCCS Policlinico San Matteo, and Department of Molecular Medicine, University of Pavia, Viale Golgi 19, 27100 Pavia, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Lavatelli
authors.affiliation: Amyloidosis Research and Treatment Center, Foundation IRCCS Policlinico San Matteo, and Department of Molecular Medicine, University of Pavia, Viale Golgi 19, 27100 Pavia, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Rognoni
authors.affiliation: Amyloidosis Research and Treatment Center, Foundation IRCCS Policlinico San Matteo, and Department of Molecular Medicine, University of Pavia, Viale Golgi 19, 27100 Pavia, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Palladini
authors.affiliation: Department of Molecular Medicine, Institute of Biochemistry, University of Pavia, via Taramelli 3b, 27100 Pavia, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Raimondi
authors.affiliation: Department of Molecular Medicine, Institute of Biochemistry, University of Pavia, via Taramelli 3b, 27100 Pavia, Italy.
authors.forename: Sofia
authors.initials: S
authors.lastname: Giorgetti
authors.affiliation: Department of Molecular Medicine, Institute of Biochemistry, University of Pavia, via Taramelli 3b, 27100 Pavia, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Monti
authors.affiliation: Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy.|Department of Physics, University of Milano-Bicocca, Piazza della Scienza 3, 20126 Milano, Italy.
authors.forename: Silvia Maria
authors.initials: SM
authors.lastname: Doglia
authors.affiliation: Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy.
authors.forename: Antonino
authors.initials: A
authors.lastname: Natalello
authors.affiliation: Amyloidosis Research and Treatment Center, Foundation IRCCS Policlinico San Matteo, and Department of Molecular Medicine, University of Pavia, Viale Golgi 19, 27100 Pavia, Italy.
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Merlini
mesh_terms: D050153:Abdominal Fat / Q000378:metabolism / Q000473:pathology; D058227:Amyloidogenic Proteins / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000737:chemistry / Q000378:metabolism; D000075363:Immunoglobulin Light-chain Amyloidosis / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D058225:Plaque, Amyloid / Q000378:metabolism* / Q000473:pathology; D066263:Protein Aggregation, Pathological / Q000378:metabolism*; D011485:Protein Binding; D000072757:Protein Conformation, beta-Strand; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D058227:Amyloidogenic Proteins; D007147:Immunoglobulin Light Chains