{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T06:03:04Z","timestamp":1782280984044,"version":"3.54.5"},"posted":{"date-parts":[[2025,4,25]]},"group-title":"Immunology","reference-count":18,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T00:00:00Z","timestamp":1745539200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"NIH\/NINDS","award":["1K22NS114363"],"award-info":[{"award-number":["1K22NS114363"]}]},{"name":"NIH\/NIGMS","award":["TME CoBRE GM121322"],"award-info":[{"award-number":["TME CoBRE GM121322"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,7,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Recent reports show that neutrophil activity plays a role in the cognitive decline associated with Alzheimer\u2019s Disease (AD). There is evidence of altered functions in neutrophils isolated from AD patients. Whether these altered functions are inherent to the AD disease state is unknown. The goal of this study was to determine if neutrophil functions are altered in AD mice and if these changes occur only after symptoms appear. To address this hypothesis, we used a primary neuronal culture model, generated from 3xTg perinatal mice, since AD is considered a CNS disease. The 3xTg primary neuronal culture gradually increase the release of A\u03b2 (40 and 42) as the culture ages. To assess neutrophil functions, neutrophils isolated from young male\/female mice (3-6 months of age) or aged male\/female mice (16-18 months of age) of WT or 3xTg mice were exposed to 3xTg primary neuronal cultures. To assess phagocytosis, we characterized the effect of neutrophils on pathogenic amyloid beta (A\u03b2) 42 levels. To assess the levels of immune modulators (cytokines, chemokines, growth factors, NETosis, and neutrophil granular content), culture media were assessed using Luminex multiplex assay. Our results show that neutrophils from young AD mice have impaired phagocytosis, as observed in a decreased ability to remove A\u03b2 and cellular debris in vitro. Neutrophils from young AD mice also increased release of pro-inflammatory cytokines, granule content, and NETs in 3xTg primary neuronal cultures. Interestingly, neutrophils from aged 3xTg mice decreased A\u03b2 levels in culture and expression of proinflammatory cytokines when compared to neutrophils from aged WT mice. These neutrophils increased their release of granule content and NETs in 3xTg primary neuronal cultures. These data show that in AD neutrophil function is altered both prodromal (young mice) and diseased (old mice) stage.<\/jats:p>","DOI":"10.1101\/2025.04.21.649766","type":"posted-content","created":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T09:00:16Z","timestamp":1745571616000},"source":"Crossref","is-referenced-by-count":1,"title":["Neutrophils from Alzheimer\u2019s Disease mice fail to phagocytose debris and show altered release of immune modulators with age"],"prefix":"10.64898","author":[{"given":"Matthew","family":"Kays","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Rockefeller Neuroscience Institute, West Virginia University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Kelly","sequence":"additional","affiliation":[{"name":"Morrisey School of Arts and Science, Boston College"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farrah","family":"McGinnis","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Rockefeller Neuroscience Institute, West Virginia University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Woods","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Rockefeller Neuroscience Institute, West Virginia University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Candice","family":"Brown","sequence":"additional","affiliation":[{"name":"Departments of Anesthesia, Indiana University School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aminata P","family":"Coulibaly","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Rockefeller Neuroscience Institute, West Virginia University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041205352372000_2025.04.21.649766v2.1","doi-asserted-by":"publisher","DOI":"10.1007\/s007020200068"},{"key":"2026041205352372000_2025.04.21.649766v2.2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21051664"},{"key":"2026041205352372000_2025.04.21.649766v2.3","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0329-4"},{"key":"2026041205352372000_2025.04.21.649766v2.4","doi-asserted-by":"crossref","unstructured":"Kong Y , Liu K , Hua T , Zhang C , Sun B , Guan Y. PET Imaging of Neutrophils Infiltration in Alzheimer\u2019s Disease Transgenic Mice. Front Neurol. 2020 Dec 10;11.","DOI":"10.3389\/fneur.2020.523798"},{"key":"2026041205352372000_2025.04.21.649766v2.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-023-02097-w"},{"key":"2026041205352372000_2025.04.21.649766v2.6","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12406"},{"key":"2026041205352372000_2025.04.21.649766v2.7","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-022-01117-1"},{"key":"2026041205352372000_2025.04.21.649766v2.8","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25159"},{"key":"2026041205352372000_2025.04.21.649766v2.9","doi-asserted-by":"publisher","DOI":"10.1023\/B:BEBM.0000010950.53560.e2"},{"issue":"1","key":"2026041205352372000_2025.04.21.649766v2.10","doi-asserted-by":"crossref","first-page":"e12873","DOI":"10.1111\/acel.12873","article-title":"Temporal and regional progression of Alzheimer\u2019s disease-like pathology in 3xTg-AD mice","volume":"18","year":"2019","journal-title":"Aging Cell [Internet]"},{"key":"2026041205352372000_2025.04.21.649766v2.11","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2012.099"},{"key":"2026041205352372000_2025.04.21.649766v2.12","doi-asserted-by":"crossref","unstructured":"Sahu MP , Nikkil\u00e4 O , L\u00e5gas S , Kolehmainen S , Castr\u00e9n E. Culturing primary neurons from rat hippocampus and cortex. Neuronal Signal. 2019 Jun;3(2):NS20180207.","DOI":"10.1042\/NS20180207"},{"key":"2026041205352372000_2025.04.21.649766v2.13","doi-asserted-by":"publisher","DOI":"10.14336\/AD.2021.0104"},{"key":"2026041205352372000_2025.04.21.649766v2.14","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0000000000000094"},{"key":"2026041205352372000_2025.04.21.649766v2.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2014.01.003"},{"issue":"1","key":"2026041205352372000_2025.04.21.649766v2.16","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s40478-022-01347-2","article-title":"Neutrophil-vascular interactions drive myeloperoxidase accumulation in the brain in Alzheimer\u2019s disease","volume":"10","year":"2022","journal-title":"Acta Neuropathol Commun"},{"key":"2026041205352372000_2025.04.21.649766v2.17","doi-asserted-by":"crossref","unstructured":"K\u00f6nnecke H , Bechmann I. The Role of Microglia and Matrix Metalloproteinases Involvement in Neuroinflammation and Gliomas. Clin Dev Immunol. 2013;2013:1\u201315.","DOI":"10.1155\/2013\/914104"},{"key":"2026041205352372000_2025.04.21.649766v2.18","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-24-07910.1996"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.04.21.649766","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:11:03Z","timestamp":1782277863000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.04.21.649766"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,25]]},"references-count":18,"URL":"https:\/\/doi.org\/10.1101\/2025.04.21.649766","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.3389\/fimmu.2025.1672768","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2025,4,25]]},"subtype":"preprint"}}