{"doi":"10.1101/2021.08.30.458295","title":"Weakly activated core inflammation pathways were identified as a central signaling mechanism contributing to the chronic neurodegeneration in Alzheimer’s disease","abstract":"Neuro-inflammation signaling has been identified as an important hallmark of Alzheimer's disease (AD) in addition to amyloid β plaques (Aβ) and neurofibrillary tangles (NFTs). However, our knowledge of neuro-inflammation is very limited; and the core signaling pathways associated with neuro-inflammation are missing. From a novel perspective, i.e., investigating weakly activated molecular signals (rather than the strongly activated molecular signals), in this study, we uncovered the core neuro-inflammation signaling pathways in AD. Our novel hypothesis is that weakly activated neuro-inflammation signaling pathways can cause neuro-degeneration in a chronic process; whereas, strongly activated neuro-inflammation often cause acute disease progression like in COVID-19. Using the two large-scale genomics datasets, i.e., Mayo Clinic (77 control and 81 AD samples) and RosMap (97 control and 260 AD samples), our analysis identified 7 categories of signaling pathways implicated on AD and related to virus infection: immune response, x-core signaling, apoptosis, lipid dysfunctional, biosynthesis and metabolism, and mineral absorption signaling pathways. More interestingly, most of genes in the virus infection, immune response and x-core signaling pathways, are associated with inflammation molecular functions. Specifically, the x-core signaling pathways were defined as a group of 9 signaling proteins: MAPK, Rap1, NF-kappa B, HIF-1, PI3K-Akt, Wnt, TGF-beta, Hippo and TNF, which indicated the core neuro-inflammation signaling pathways responding to the low-level and weakly activated inflammation and hypoxia, and leading to the chronic neuro-degeneration. The core neuro-inflammation signaling pathways can be used as novel therapeutic targets for effective AD treatment and prevention.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":215187,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9483,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":266771,"name":"Abdallah M. Eteleeb","orcid":"0000-0001-9045-250X","position":1,"is_corresponding":false},{"id":240471,"name":"William Buchser","orcid":"0000-0002-6675-6359","position":2,"is_corresponding":false},{"id":399046,"name":"Guoqiao Wang","orcid":null,"position":3,"is_corresponding":false},{"id":321049,"name":"Chengjie Xiong","orcid":"0000-0003-0044-4499","position":4,"is_corresponding":false},{"id":225274,"name":"Philip Payne","orcid":"0000-0002-9532-2998","position":5,"is_corresponding":false},{"id":301877,"name":"Eric McDade","orcid":"0000-0002-6764-3866","position":6,"is_corresponding":false},{"id":301876,"name":"Celeste M. Karch","orcid":"0000-0002-6854-5547","position":7,"is_corresponding":false},{"id":27580,"name":"Oscar Harari","orcid":"0000-0002-2635-6975","position":8,"is_corresponding":false},{"id":230680,"name":"Carlos Cruchaga","orcid":"0000-0002-0276-2899","position":9,"is_corresponding":false},{"id":368999,"name":"Fuhai Li","orcid":"0000-0002-3773-146X","position":0,"is_corresponding":true}],"reference_count":40,"raw_metadata":null,"created_at":"2026-07-18T23:52:51.201033Z","pmid":"34494019","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":[]}