Top-Down Proteomics of Human Saliva Highlights Anti-inflammatory, Antioxidant, and Antimicrobial Defense Responses in Alzheimer Disease.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34121996", "kind": "science-record", "revision": 7, "content_hash": "sha256:c4fbd887b0bbaf676a5f047333d601000290fab1caa2f6c9e75973a27f353e19", "created_at": "2026-11-01T15:41:38Z", "updated_at": "2026-11-01T22:03:56Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Top-Down Proteomics of Human Saliva Highlights Anti-inflammatory, Antioxidant, and Antimicrobial Defense Responses in Alzheimer Disease.", "doi": "10.3389/fnins.2021.668852", "pmid": "34121996", "authors": ["Cristina Contini", "Alessandra Olianas", "Simone Serrao", "Carla Deriu", "Federica Iavarone", "Mozhgan Boroumand", "Alessandra Bizzarro", "Alessandra Lauria", "Gavino Faa", "Massimo Castagnola", "Irene Messana", "Barbara Manconi", "Carlo Masullo", "Tiziana Cabras"], "journal": "Frontiers in neuroscience", "year": 2021, "abstract": "Alzheimer disease (AD) is the most prevalent neurodegenerative disease in the elderly, characterized by accumulation in the brain of misfolded proteins, inflammation, and oxidative damage leading to neuronal cell death. By considering the viewpoint that AD onset and worsening may be influenced by environmental factors causing infection, oxidative stress, and inflammatory reaction, we investigated the changes of the salivary proteome in a population of patients with respect to that in healthy controls (HCs). Indeed, the possible use of saliva as a diagnostic tool has been explored in several oral and systemic diseases. Moreover, the oral cavity continuously established adaptative and protective processes toward exogenous stimuli. In the present study, qualitative/quantitative variations of 56 salivary proteoforms, including post-translationally modified derivatives, have been analyzed by RP-HPLC-ESI-IT-MS and MS/MS analyses, and immunological methods were applied to validate MS results. The salivary protein profile of AD patients was characterized by significantly higher levels of some multifaceted proteins and peptides that were either specific to the oral cavity or also expressed in other body districts: (i) peptides involved in the homeostasis of the oral cavity; (ii) proteins acting as ROS/RNS scavengers and with a neuroprotective role, such as S100A8, S100A9, and their glutathionylated and nitrosylated proteoforms; cystatin B and glutathionylated and dimeric derivatives; (iii) proteins with antimicrobial activity, such as α-defensins, cystatins A and B, histatin 1, statherin, and thymosin β4, this last with a neuroprotective role at the level of microglia. These results suggested that, in response to injured conditions, Alzheimer patients established defensive mechanisms detectable at the oral level. Data are available via ProteomeXchange with identifier PXD021538.", "claims": [{"id": "claim-method", "statement": "A comparison between the groups of patients and controls has been performed with Mann–Whitney and Welch-corrected t-tests, depending on the distribution (skewed or normal) and the variance (unequal or homogeneous).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34121996", "locator": "sections[7] \"Quantification and Statistical Analysis\" paragraph 2", "quote": "A comparison between the groups of patients and controls has been performed with Mann–Whitney and Welch-corrected t-tests, depending on the distribution (skewed or normal) and the variance (unequal or homogeneous)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. 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This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:PXD021538"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:PXD021538"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34121996", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fnins.2021.668852", "sha256": "sha256:7203baf73bf8bf3bb2391d7a15c8164ebab598c10d08019a608c451456d62fe4", "bytes": 61873, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fnins.2021.668852", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8189262", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:PXD021538", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=PXD021538", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "PXD021538", "version": null, "note": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: https://www.ebi.ac.uk/pride/archive/, PXD021538.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: https://www.ebi.ac.uk/pride/archive/, PXD021538.", "access_statement_kind": "data_availability_statement", "sample_accessions": [], "sample_count": null, "group_sizes": null, "group_sizes_basis": null, "platform": null, "taxon": null, "title": "Top-down proteomics of human saliva in Alzheimer disease", "resolution_checked_at": "2026-10-31T18:35:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:34121996:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:850a7afae1aeba6d09965bdce8303c9bcc5efe394302680fc710bcb3f45b9c6f", "bytes": 2345, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[1]#T1", "version": null, "note": "XIC peak areas values (mean ± SD) normalized on total protein concentration and frequencies of salivary proteins/peptides resulted to levels significantly different between the AD group and HC group.", "structure": {"pmcid": "PMC8189262", "section_index": 11, "section_title": "Results", "row_count": 27, "column_count": 4}, "table": {"label": "TABLE 1", "caption": "XIC peak areas values (mean ± SD) normalized on total protein concentration and frequencies of salivary proteins/peptides resulted to levels significantly different between the AD group and HC group.", "rows": [["Protein/peptide", "XIC peak areas × 105 (mean ± SD) and frequency", "p-Values"], ["", "AD", "HC", "AD vs HC"], ["P-C peptide", "9.8 ± 7.7 (33/35)", "5.9 ± 4.4 (34/34)", "p = 0.02 AD↑"], ["Statherin 2P", "9.7 ± 9.6 (35/35)", "1.1 ± 0.9 (33/34)", "p < 0.0001 AD↑"], ["Stath. desF43", "1.5 ± 1.3 (35/35)", "0.4 ± 0.7 (33/34)", "p < 0.0001 AD↑"], ["Stath. des1–9", "0.6 ± 0.6 (29/37)", "0.08 ± 0.1 (24/34)", "p < 0.0001 AD↑"], ["Stath. des1–13", "0.2 ± 0.3 (24/35)", "0.08 ± 0.1 (16/34)", "p = 0.01 AD↑"], ["Hst-1 1P", "1.6 ± 1.5 (33/35)", "0.8 ± 0.8 (28/34)", "p = 0.01 AD↑"], ["Hst-1 0P", "0.3 ± 0.4 (24/35)", "0.1 ± 0.2 (17/34)", "p = 0.02 AD↑"], ["Cyst A", "1.9 ± 1.6 (32/35)", "1.0 ± 0.9 (29/34)", "p = 0.007 AD↑"], ["Cyst B-SSG", "0.9 ± 1.2 (29/35)", "0.3 ± 0.3 (27/34)", "p = 0.006 AD↑"], ["Cyst-B-SSC", "0.2 ± 0.3 (20/35)", "0.08 ± 0.1 (18/34)", "•"], ["Cyst B-SS dimer", "0.6 ± 0.5 (31/35)", "0.2 ± 0.3 (27/34)", "p = 0.0006 AD↑"], ["Cyst B tot", "1.7 ± 1.9 (33/35)", "0.6 ± 0.6 (27/34)", "p = 0.002 AD↑"], ["α-defensin 1", "1.8 ± 2.0 (32/35)", "0.5 ± 0.6 (24/34)", "p = 0.0001 AD↑"], ["α-defensin 2", "1.2 ± 1.3 (30/35)", "0.4 ± 0.4 (27/34)", "p = 0.0009 AD↑"], ["α-defensin 3", "0.6 ± 0.5 (25/35)", "0.2 ± 0.3 (17/34)", "p = 0.0003 AD↑"], ["α-defensin 4", "0.2 ± 0.3 (13/35)", "0.05 ± 0.1 (11/34)", "p = 0.01 AD↑"], ["α-defensin tot", "3.9 ± 4.0 (32/35)", "1.2 ± 1.5 (24/34)", "p = 0.0005 AD↑"], ["Tβ4", "0.7 ± 0.8 (25/35)", "0.2 ± 0.4 (16/34)", "p = 0.01 AD↑"], ["S100A8", "0.6 ± 1.3 (9/35)", "0.04 ± 0.2 (2/34)", "p = 0.02 AD↑"], ["S100A8 hyperoxidized", "0.2 ± 0.4 (5/35)", "0.04 ± 0.2 (3/34)", "•"], ["S100A8-SNO", "0.8 ± 1.8 (12/35)", "Not detected", "NA"], ["S100A8 tot", "1.6 ± 2.7 (22/35)", "0.08 ± 0.2(5/34)", "p < 0.0001 AD↑"], ["S100A9(S) (all proteoforms)", "3.3 ± 3.2 (32/35)", "0.5 ± 0.8 (16/34)", "p < 0.0001 AD↑"], ["S100A9(L)-SSG", "1.5 ± 2.4 (22/35)", "0.3 ± 0.4 (16/34)", "p = 0.004 AD↑"], ["S100A9 tot", "4.8 ± 5.4 (33/35)", "0.9 ± 1.2 (19/35)", "p < 0.0001 AD↑"]], "row_count": 27, "column_count": 4, "numeric_cells": 90, "header_rows": 2, "locator": "section[11]/table-wrap[1]#T1"}}], "gaps": ["asset:data:geo:PXD021538 not downloaded", "asset:data:geo:PXD021538 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "welch_t_test", "label": "Group comparison", "dsl_operations": ["welch_t"], "missing_operations": [], "expressible": true, 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