Study methods (concise)
Large-scale, isobaric tandem mass tag (TMT) proteomics was performed on human post-mortem cortex with rigorous batch randomization and pooled global internal standards. Peptides were generated by urea lysis followed by Lys-C/Trypsin digestion, high-pH fractionation, and LC–MS/MS on Orbitrap platforms. Spectra were searched with Proteome Discoverer/Sequest HT against UniProt, controlling peptide/protein FDR at <1%. Reporter ion abundances were corrected and summarized at the protein level, followed by TAMPOR normalization to remove intra- and inter-batch effects while preserving biological variance. Outliers were removed using network connectivity metrics, and covariates (age, sex, PMI) were regressed with diagnosis protected.
- Brain region used: Dorsolateral prefrontal cortex (BA9).
Data availability & downloads
Data were obtained from Synapse: syn25006611 / Deep Consensus Proteomics.
- Consensus – Banner (BA-9): raw TMT data from dorsolateral prefrontal cortex and associated study metadata in the Banner Sun Health Research Institute cohort.
- Consensus – ROSMAP (BA-9): raw TMT data from dorsolateral prefrontal cortex and metadata in the Religious Orders Study and Memory and Aging Project cohort.
Citation
Johnson, E.C.B., Carter, E.K., Dammer, E.B. et al. Large-scale deep multi-layer analysis of Alzheimer’s disease brain reveals strong proteomic disease-related changes not observed at the RNA level. Nat Neurosci 25, 213–225 (2022). https://doi.org/10.1038/s41593-021-00999-y
Received: 22 Mar 2021 · Accepted: 08 Dec 2021 · Published: 03 Feb 2022 · Issue: Feb 2022
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