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. 2023 Jul 24;146(3):451–475. doi: 10.1007/s00401-023-02611-y

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© The Author(s) 2023, corrected publication 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — Enrichment analysis of the human ALS spinal cord synaptic proteome. a Schematic diagram shows the experimental workflow. Synaptically-enriched fractions were collected using fresh frozen human spinal cord tissue from age and gender-matched controls, sporadic ALS (sALS) and C9ORF72-RE + ve donors. After Tandem Mass Tag (TMT) labelling, proteome was examined using liquid chromatography, mass spectrometry-based quantification and identification (LC–MS/MS). Collected MS data were analysed using MaxQuant proteomics software. b Heatmap shows genotypic-specific protein changes using hierarchical clustering with Euclidean distance. c The number of up- and down-regulated proteins were counted using the control normalized ratiometric values on a threshold of 20% ≤ change in each direction. d, e Bioinformatics analysis revealed the top enriched KEGG pathways and Gene Ontology (GO) terms using the up- and down-regulated protein IDs. Colorized dot plots and bar graphs were created based on fold enrichment and gene counts/pathway. f Synaptic enrichment analysis using down-regulated protein IDs by the SynGO database shows enhancement in presynaptic terms including synaptic vesicle cycle