Kim, C. C. | bioRxiv Science

bioRxiv2026

Rapid Mechanistic Bridging of an Alzheimer's Disease Plasma Protein Staging Panel Across Brain Proteomics Cohorts

Background: Blood-based biomarkers are transforming Alzheimer's Disease (AD) diagnosis and staging. Recent multi-protein plasma panels accurately identify individuals with advanced Braak pathology, but whether these circulating biomarkers truly reflect the molecular remodeling underlying AD neuropathology remains unclear. Pre-existing datasets could answer such questions, but their reuse requires harmonized protein expression data, standardized sample annotations, and consistent study metadata. Methods: A recently reported seven-protein plasma staging panel was evaluated across multiple post-mortem proteomics brain cohorts using pre-structured datasets on the Tesorai platform. Five datasets with Braak stage data were identified and re-analyzed. A linear model was used to distinguish late (V-VI) from early Braak stage (0-IV). Because phosphorylated tau 217 (p-tau217) and amyloid beta 1-40 (A{beta}40) were not reported for any studies, raw spectra were reprocessed to quantify these proteoforms. Results: Across the cohorts, the plasma-derived biomarker panel consistently discriminated early from late disease despite heterogeneous protein coverage. Reprocessing of raw spectra recovered tau phosphopeptides absent from the original protein summaries, enabling inclusion of p-tau217, while A{beta}40 remained undetected. Together, these findings show that proteins comprising a recently proposed blood-based staging panel are associated with proteomic remodeling in the AD brain across independent cohorts. Conclusions: These findings provide biological validation for a recently proposed blood-based seven-protein staging panel by demonstrating that its constituent biomarkers are associated with disease-stage proteomic changes in AD brain tissue. More broadly, re-mining legacy mass spectrometry data for disease-relevant proteoforms, combined with pre-structured datasets, can accelerate evaluation of emerging blood-based biomarkers against neuropathological and molecular features of disease.

neuroscience↗

bioRxiv2023

Multi-omic Profiling Reveals Early Immunological Indicators for Identifying COVID-19 Progressors

The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a rapid response by the scientific community to further understand and combat its associated pathologic etiology. A focal point has been on the immune responses mounted during the acute and post-acute phases of infection, but the immediate post-diagnosis phase remains relatively understudied. We sought to better understand the immediate post-diagnosis phase by collecting blood from study participants soon after a positive test and identifying molecular associations with longitudinal disease outcomes. Multi-omic analyses identified differences in immune cell composition, cytokine levels, and cell subset-specific transcriptomic and epigenomic signatures between individuals on a more serious disease trajectory (Progressors) as compared to those on a milder course (Non-progressors). Higher levels of multiple cytokines were observed in Progressors, with IL-6 showing the largest difference. Blood monocyte cell subsets were also skewed, showing a comparative decrease in non-classical CD14-CD16+ and intermediate CD14+CD16+ monocytes. Additionally, in the lymphocyte compartment, CD8+ T effector memory cells displayed a gene expression signature consistent with stronger T cell activation in Progressors. Importantly, the identification of these cellular and molecular immune changes occurred at the early stages of COVID-19 disease. These observations could serve as the basis for the development of prognostic biomarkers of disease risk and interventional strategies to improve the management of severe COVID-19. One Sentence SummaryImmunological changes associated with COVID-19 progression can be detected during the early stages of infection.

immunology↗