Diagram of experimental workflow. (a) Sample preparation for label-free quantitative proteomics (Discovery Phase A). Ten cases each of AD, FTLD-U, and Control were pooled by diagnosis and sequentially extracted. Urea samples were then analyzed by shotgun LC-MS/MS. (b) Sample preparation for quantitative proteomics based on culture derived isotopic tags (Discovery Phase B). Four cases each of FTLD-U and control were pooled by diagnosis and sequentially extracted. Urea fractions for each diagnosis were mixed (1:1) with HEK293 lysate labeled with heavy stable isotopes of arginine and lysine. The heavy labeled peptides served as internal standards following analysis by LC-MS/MS. (c) Validation of identification of Septin 11 enrichment in FTLD-U using three independent methods.