{"doi":"10.3233/jad-210091","title":"Neuronal Cell Cycle Re-Entry Enhances Neuropathological Features in <i>App</i> <sup> <i>NLF</i> </sup> Knock-In Mice","abstract":"BACKGROUND: Aberrant cell cycle re-entry is a well-documented process occurring early in Alzheimer's disease (AD). This is an early feature of the disease and may contribute to disease pathogenesis. OBJECTIVE: To assess the effect of forced neuronal cell cycle re-entry in mice expressing humanized Aβ, we crossed our neuronal cell cycle re-entry mouse model with AppNLF knock-in (KI) mice. METHODS: Our neuronal cell cycle re-entry (NCCR) mouse model is bitransgenic mice heterozygous for both Camk2a-tTA and TRE-SV40T. The NCCR mice were crossed with AppNLF KI mice to generate NCCR-AppNLF animals. Using this tet-off system, we triggered NCCR in our animals via neuronal expression of SV40T starting at 1 month of age. The animals were examined at the following time points: 9, 12, and 18 months of age. Various neuropathological features in our mice were evaluated by image analysis and stereology on brain sections stained using either immunofluorescence or immunohistochemistry. RESULTS: We show that neuronal cell cycle re-entry in humanized Aβ plaque producing AppNLF KI mice results in the development of additional AD-related pathologies, namely, pathological tau, neuroinflammation, brain leukocyte infiltration, DNA damage response, and neurodegeneration. CONCLUSION: Our findings show that neuronal cell cycle re-entry enhances AD-related neuropathological features in AppNLF mice and highlight our unique AD mouse model for studying the pathogenic role of aberrant cell cycle re-entry in AD.","journal":"Journal of Alzheimer s Disease","year":2021,"id":197927,"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":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9611,"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":772465,"name":"Katherine A. Stangis","orcid":"0009-0009-6071-0366","position":1,"is_corresponding":false},{"id":251064,"name":"Takashi Saito","orcid":"0000-0002-9659-9251","position":2,"is_corresponding":false},{"id":251065,"name":"Takaomi C. Saido","orcid":"0000-0003-1970-6903","position":3,"is_corresponding":false},{"id":426686,"name":"Kevin H. J. Park","orcid":"0000-0003-3130-7075","position":4,"is_corresponding":false},{"id":427525,"name":"Tomás Barrett","orcid":null,"position":0,"is_corresponding":true}],"reference_count":115,"raw_metadata":null,"created_at":"2026-07-18T23:50:27.616568Z","pmid":"34219712","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":[]}