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Curr Med Chem. 2017 Oct 3. doi: 10.2174/0929867324666171003113019. [Epub ahead of print]

Hyphenated Mass Spectrometry Techniques in the Diagnosis of Amyloidosis.

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1
University of Gdańsk, Faculty of Chemistry, Wita Stwosza 63, 80-308 Gdańsk. Poland.

Abstract

Amyloidoses are a group of diseases caused by the extracellular deposition of proteins forming amyloid fibrils. The amyloidosis is classified according to the main protein or peptide that constitutes the amyloid fibrils. The most effective methods for the diagnosis of amyloidosis are based on mass spectrometry. Mass spectrometry enables confirmation of the identity of the protein precursor of amyloid fibrils in biological samples with very high sensitivity and specificity, which is crucial for proper amyloid typing. Due to the fact that biological samples are very complex, mass spectrometry is usually connected with techniques such as liquid chromatography or capillary electrophoresis, which enable the separation of proteins before MS analysis. Therefore mass spectrometry constitutes an important part of so called "hyphenated techniques" combining, preferentially in-line, different analytical methods to provide comprehensive information about the studied problem. Hyphenated methods are very useful in discovery of biomarkers in different types of amyloidosis. In systemic forms of amyloidosis the analysis of aggregated proteins is usually performed based on tissues obtained during a biopsy of an affected organ or a subcutaneous adipose tissue. In some cases, when the diagnostic biopsy is not possible due to the fact that amyloid fibrils are formed in organs like the brain (Alzheimer's disease), the study of biomarkers presented in body fluids can be carried out. Currently, large-scale studies are performed to find and validate more effective biomarkers, which can be used in diagnostic procedures. We would like to present the methods connected with mass spectrometry which are used in diagnosis of amyloidosis based on analysis of proteins occurring in tissues, blood and cerebrospinal fluid.

KEYWORDS:

; amyloidosis; biomarker; diagnosis; neurodegeneration; proteomics; tandem mass spectrometry

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