{"doi":"10.3233/adr-220029","title":"<i>Porphyromonas gingivalis</i> Conditioned Medium Induces Amyloidogenic Processing of the Amyloid-β Protein Precursor upon <i>in vitro</i> Infection of SH-SY5Y Cells","abstract":"Background: Cleavage of the amyloid-β protein precursor (AβPP) mediated by host secretase enzymes, releases several fragments including amyloid-β (Aβ 40 and Aβ 42 ). Objective: To determine if Porphyromonas gingivalis conditioned medium cleaved AβPP to release Aβ 40 and Aβ 42 . Methods: The SH-SY5Y cell line was challenged, in vitro, with P. gingivalis (Pg381) conditioned medium in the presence/absence of cytokines. The cells and their supernatants were assessed for AβPP cleavage fragments by immunoblotting and transmission electron microscopy. Results: Western blotting of the cell lysates with the anti-AβPP C-terminal antibody demonstrated variable molecular weight bands corresponding to full length and fragmented AβPP in lanes treated with the following factors: Tryptic soy broth (TSB), Pg381, IL-6, Pg381 + IL-1β, and Pg381 + TNF-α. The low molecular weight bands corresponding to the C99 dimerized fragment were observed in the Pg381 and interlukin-6 (IL-6) treated groups and were significantly more intense in the presence of Pg381 with either IL-6 or TNF-α. Bands corresponding to the dimerized C83 fragment were observed with cells treated with TNF-α alone and with Pg381 combined with IL-1β or IL-6 or TNF-α. The anti-Aβ antibody detected statistically significant Aβ 40 and Aβ 42 , levels when these two Aβ species were pooled across test samples and compared to the untreated group. Electron microscopic examination of the supernatants demonstrated insoluble Aβ 40 and Aβ 42 . Conclusion: These observations strongly imply that AβPP is an infection responsive protein cleaved via the amyloidogenic pathway on exposure to conditioned medium and in the presence of pro-inflammatory mediators.","journal":"Journal of Alzheimer s Disease Reports","year":2022,"id":252083,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":24,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9624,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":896559,"name":"Christopher von Ruhland","orcid":null,"position":1,"is_corresponding":false},{"id":896017,"name":"Richard Welbury","orcid":"0000-0002-9322-2440","position":2,"is_corresponding":false},{"id":896018,"name":"Sasanka S. Chukkapalli","orcid":"0000-0001-9063-6907","position":3,"is_corresponding":false},{"id":896019,"name":"Sim K. Singhrao","orcid":"0000-0001-9573-5963","position":4,"is_corresponding":false},{"id":896016,"name":"Shalini Kanagasingam","orcid":"0000-0001-6274-5188","position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":null,"created_at":"2026-07-19T00:24:46.226372Z","pmid":"36275415","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}