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Proteomics in Diagnostic Neuropathology

In the "postgenome" era, attention has turned to the proteome as a source of complementary diagnostic and prognostic information. Recent advances in imaging mass spectrometry (IMS) uses matrix-assisted laser desorption ionization-mass spectrometry (MALDI-MS) to acquire up to 1,000 individual protein signals within the molecular weight range of 2,000 to over 100,000 in specific areas of tissue sections. The systematic investigation of these sections permits creation of specific molecular weight images (ion density maps) for each signal detected. Analysis of these images can reveal a collection of unique protein changes, or a "protein signature", of diagnostic and prognostic value. These signatures may also afford assessment of disease progression and tissue response to treatments. Combined with histology and molecular genetic analyses, new proteomic techniques should refine subclassifications and provide defining information about the pathogenesis of many central and peripheral nervous system diseases.