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P2‐219: METHOD DEVELOPMENT AND PROTEOMIC ANALYSIS OF DEPLETED PLASMA FOR BIOMARKER DISCOVERY IN NEURODEGENERATIVE DISEASES
Author(s) -
Virk Gurjeet Kaur,
Poljak Anne,
Braidy Nady,
Sachdev Perminder S.
Publication year - 2019
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2019.06.2626
Subject(s) - biomarker discovery , proteomics , biomarker , computational biology , shotgun , biology , chemistry , bioinformatics , biochemistry , gene
reveal new protein modules that correlated with disease and were unrelated to those identified in our previous network. RNA binding proteins emerged as a class of proteins altered between AsymAD and AD, and were enriched in network modules that correlated with AD pathology. We developed a proteogenomic approach to investigate RNA splicing events that may be altered by RNA binding protein changes in AD. The increased proteome depth afforded by our TMT pipeline allowed us to identify and quantify a large number of alternatively spliced protein isoforms in brain, including AD risk factors such as BIN1, PICALM, PTK2B, and FERMT2. Many of the new AD protein network modules were enriched in alternatively spliced proteins and correlated with molecular markers of AD pathology and cognition. Conclusions: RNA binding proteins and RNA splicing are altered in AD. Further analysis of the AD brain proteome will continue to yield new insights into the biological basis of AD.