Using mass spectrometry to generate the brain proteome from multiple tauopathies, including CTE cases with increasing neuropathologic stage, and compared findings to control cases. By using CTE cases with increasing pathologic stage, we may be able to identify disease related changes that are important to the progression of CTE. We then used differential protein expression and weighted gene co-expression network analysis to identify significant protein changes in the CTE cases and to identify subgroups of related genes/proteins to provide clues about disease related pathologies.

In addition to identifying a progressive neurodegeneration phenotype in CTE cases, the proteomic findings demonstrated early enrichment of immunoglobulins in CTE compared to both control cases and other tauopathies. The findings were validated with protein blotting and with immunohistochemical labeling of immunoglobulins in CTE tissue, particularly in CTE-II cases.

The proteomic sequencing identified a progressive neurodegeneration signature with increasing neuropathologic stage. Interestingly, the immunoglobulin signature was specific for the TBI-induced tauopathy. The lack of significant enrichment in CTE-I cases suggests that this is likely not immunoglobulin extravasation as a result of previous TBI. Future studies will investigate the role of enriched immunoglobulins TBI-induced neurodegeneration.