Figure 2

Case demographic summary and representation of mass spectrometry (MS) methods. (A) Summary demographics of cases. Data is presented as mean (standard deviation). Last valid global cognition Z-score is a ROSMAP cohort-wide Z-score normalised summary value encompassing a battery of cognitive tests assessing 5 cognitive domains at the last valid clinical visit prior to death. Global pathology Z-score is a quantitative summary score of amyloid and tau pathology burden averaged across 5 brain regions presented as a ROSMAP cohort-wide Z-score. MMSE = Mini Mental State Examination. (B) MS methods for the quantification of brain proteoforms from 102 participants within control, frail, resilient and dementia diagnostic classes. Protein was extracted and samples were tandem mass tag (TMT) labelled alongside a pooled reference sample. Samples were mixed and size-selected, for peptide enrichment, via a 50 kDa molecular weight filter. Offline fractionation was employed, resulting in six analytical fractions per plex, each of which underwent data-dependent acquisition MS. Data were collected and analysed at the MS2 level. MS schematic taken from Quinn et al.¹⁹.