Development and Validation of Mass Spectrometry-Based Targeted Analysis for Amyloid Proteins

Purpose: Amyloidosis is caused by the extracellular deposition of insoluble fibrils and results in multiple organ dysfunctions. Accurate typing of amyloid is mandatory to decide the optimal treatment for amyloidosis. Experimental design: A mass spectrometry-based test combined with laser microdissection (LMD/MS) has been widely used even in the tricky cases that cannot be discriminated by immunohistochemical staining. However, shotgun proteomics analysis obligatorily requires not only expensive instruments but also highly-experienced specialists to interpret the analysis. Thus, a method of LMD combined with multiple reaction monitoring mass spectrometry (MRM-MS) that can detect three most common types of amyloidosis is developed. Results: The diagnostic method is tested in 16 Congo red-positive tissues and 10 Congo red-negative control tissues. The results showed better performance in amyloidosis typing than other analytical techniques. Conclusion and clinical relevance: This novel diagnostic approach can achieve successful amyloidosis typing with high specificity and sensitivity and be implemented more easily in general clinical laboratories.