Amyloidosis subtyping by laser-capture microdissection and tandem mass spectrometry
Peter Mollee1
1 Pathology Queensland and Queensland Amyloidosis Centre, Princess Alexandra Hospital, Brisbane, Australia
Amyloidosis is a rare but devastating condition caused by deposition of misfolded proteins as aggregates in the extracellular tissues of the body, leading to impairment of organ function. Many, but not a limitless number of proteins can cause amyloidosis, the most common being transthyretin (ATTR), immunoglobulin light chain (AL), serum amyloid A protein (AA) and the alpha chain of fibrinogen (AFib). For patients with systemic amyloidosis, unequivocal identification of the amyloid type is mandatory for optimal treatment.
Mass spectrometry-based proteomics has become the new gold standard for amyloid typing, used in conjunction with current clinical and antibody-based tests. This proteomic diagnostic method has been developed at the Queensland Amyloidosis Centre in Brisbane as a collaboration between Pathology Queensland and the Translational research Institute. It involves an initial selection of amyloid deposits from formal-fixed paraffin-embedded tissue biopsy samples by laser-capture microdissection followed by high performance liquid chromatography and tandem mass spectrometry, and then bioinformatic analysis to details the protein composition of the dissected amyloid. In light of its clear benefit to patients, and with the availability of new treatments for specific amyloid types, mass spectrometry based proteomics for amyloid typing should be implemented broadly.
