Identification of amyloid precursor protein from autopsy and biopsy specimens using LMD-LC-MS/MS: the experience at Kumamoto University

Mass spectrometry-based proteomics in clinical practice amyloid typing: state-of-the-art from a French nationwide cohort

“…Mass-spectrometry-based proteomics amyloid typing in clinical practice: state-of-the-art from a French nationwide cohort Short title: amyloid typing using mass spectrometry Magali Colombat 1 , Margot Gaspard 1 , Mylène Camus 2,3 , Jessica Dalloux-Chioccioli 1 , Audrey Delas 1 , Elsa Poullot 4 , Anissa Moktefi 4,5 , Arnaud François 6 , Anne Moreau 7 , Jean-Bapiste Gibier 8 , Pierre Raynaud 9 , Antoine Huart 10 , Alexis Piedrafita 10,11 , Julia Gilhodes 12 , Olivier Lairez 13 , Gilles Grateau 14 , Sophie Georgin-Lavialle 14 , Hervé Maisonneuve 15 , Philippe Moreau 16 , Arnaud Jaccard 17 , Franck Bridoux 18 , Violaine Plante-Bordeneuve 5,19 Amyloidosis refers to a large spectrum of diseases, all characterized by the deposition of extracellular misfolded proteins in the form of insoluble highly ordered amyloid fibrils in one (localized amyloidosis) or multiple tissues (systemic amyloidosis). [1][2][3] Amyloid deposits progressively disrupt tissue structure and exert toxic effect on the adjacent cells that ultimately result in organ dysfunction.…”

“…Therefore, laser microdissection from formalin-fixed paraffin-embedded (FFPE) tissue combined with tandem mass spectrometry (LMD-MS/MS) has been developed and progressively implemented in routine practice. [6][7][8][9][10][11][12][13] The rationale for the application of this method is based on the relative abundance of amyloid protein that usually corresponds to one of the dominant proteins within the studied biopsy sample. [6][7][8][9][10][11][12][13] In recent years, MS-based proteomics has become the reference method because of its excellent identification capacity.…”

“…[6][7][8][9][10][11][12][13] The rationale for the application of this method is based on the relative abundance of amyloid protein that usually corresponds to one of the dominant proteins within the studied biopsy sample. [6][7][8][9][10][11][12][13] In recent years, MS-based proteomics has become the reference method because of its excellent identification capacity. [6][7][8][9][10][11][12][13] However, its performance on various tissues/organs remains still limited to a few expert centers worldwide.…”

The Clinical Impact of Proteomics in Amyloid Typing

“…Since then, 13 cohort studies from Australia, Japan, United Kingdom, Czech Republic, Denmark, South Korea, and the United States independently confirmed the accuracy of LMD-LC-MS/MS in amyloid typing (Table ). 9,11,[12][13][14][15][16][17][18][19][20][21][22] IMPACT OF PROTEOMICS ON PATIENT OUTCOMES The advent of routine clinical use of LC-MS/ MS for amyloid typing has had a profound effect on patient care. Evaluation of the overall impact of proteomics in amyloid typing was first highlighted in the Australian study by Mollee et al, in which 24% of the cohort's clinical treatment was altered as a result of the LC-MS/MS test.…”

An unusual case of Aβ2M amyloid deposition in bladder cancer in a non‐dialysis patient

“…Laser microdissection‐liquid chromatography tandem mass spectrometry (LCMS/MS) proteomic analysis was then performed at Kumamoto University, as previously described, to confirm amyloid precursor protein. LCMS/MS analysis results showed that β2‐m was the most commonly identified protein.…”