{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T04:46:56Z","timestamp":1782190016768,"version":"3.54.5"},"reference-count":39,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100017510","name":"UK Dementia Research Institute","doi-asserted-by":"publisher","award":["UK DRI\u20103203"],"award-info":[{"award-number":["UK DRI\u20103203"]}],"id":[{"id":"10.13039\/501100017510","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      Microglia undergo profound structural and functional changes during Alzheimer's disease, yet the earliest stages of morphological remodelling that occur prior to amyloid deposition remain poorly defined. We hypothesised that microglia in the hippocampus of\n                      <jats:italic>App<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>NL\u2010G\u2010F<\/jats:italic>\n                      <\/jats:sup>\n                      mice would exhibit early, region\u2010specific structural adaptations before local plaque formation, reflecting an initial phase of disease\u2010associated structural remodelling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Two\u2010month\u2010old\n                      <jats:italic>App<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>NL\u2010G\u2010F<\/jats:italic>\n                      <\/jats:sup>\n                      and wildtype mice were examined using high\u2010resolution confocal microscopy of Iba1\u2010labelled microglia in the dorsal CA1 apical field. Automated three\u2010dimensional reconstructions were generated in Imaris, and quantitative morphometric analyses quantified cell density, Iba1 coverage, process topology and Sholl\u2010based arbor complexity. Statistical analyses were performed using linear mixed\u2010effects models incorporating sex as a fixed factor in all analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Microglial density and total Iba1 coverage were unaffected in\n                      <jats:italic>App<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>NL\u2010G\u2010F<\/jats:italic>\n                      <\/jats:sup>\n                      mice at this age. In contrast, Sholl analysis revealed significant genotype\u2010dependent reductions in process intersections and total process length, accompanied by reduced individual\u2010cell territorial coverage, indicating an early contraction of the surveillance arbor independent of cell number.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      These findings demonstrate that hippocampal microglia in\n                      <jats:italic>App<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>NL\u2010G\u2010F<\/jats:italic>\n                      <\/jats:sup>\n                      mice undergo an early, coordinated structural remodelling before local amyloid deposition becomes apparent. This preplaque adaptation defines an early structural remodelling of hippocampal microglia prior to evident local amyloid deposition, providing new insight into the earliest structural adaptations associated with neuroimmune engagement in\n                      <jats:sc>AD<\/jats:sc>\n                      pathogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nan.70082","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T14:25:25Z","timestamp":1779805525000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Early Regional Microglial Remodelling in the Hippocampus of the\n                    <i>App<\/i>\n                    <sup>\n                      <i>NL\u2010G\u2010F<\/i>\n                    <\/sup>\n                    Alzheimer's Model"],"prefix":"10.1111","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2557-2887","authenticated-orcid":false,"given":"Ryan J.","family":"Bevan","sequence":"first","affiliation":[{"name":"UK Dementia Research Institute at Cardiff University Cardiff University  Cardiff UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6449-0801","authenticated-orcid":false,"given":"Jessica F.","family":"Minett","sequence":"additional","affiliation":[{"name":"School of Biosciences, Singelton Campus Swansea University  Swansea UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice L.","family":"Smith","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute at Cardiff University Cardiff University  Cardiff UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4699-6205","authenticated-orcid":false,"given":"Ana Cardus","family":"Figueras","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute at Cardiff University Cardiff University  Cardiff UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0163-1421","authenticated-orcid":false,"given":"Philip R.","family":"Taylor","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute at Cardiff University Cardiff University  Cardiff UK"},{"name":"Systems Immunity Research Institute, Heath Park Cardiff University  Cardiff UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1110647"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2022.10.020"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2025.04.009"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fninf.2023.1211188"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.03.026"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1472"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4363\u201008.2009"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306\u20104522(90)90229\u2010w"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4158\u201011.2011"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.08.001"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20101\u20104939\u20109658\u20102_2"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.125"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.11.004"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2802"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588\u2010019\u20100358\u20102"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588\u2010022\u201001024\u2010z"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3916"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.05.018"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7176"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3697"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nlm.2016.07.001"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2018.10.026"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00308809"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593\u2010022\u201001167\u20106"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010023\u201001588\u20100"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201054779\u2010w"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2017.01.003"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12149"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2016.05.003"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.03.099"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003\u2010021\u201002259\u2010y"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.868448"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac257"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5572\u201008.2009"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.12.002"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.07.023"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neures.2025.104959"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024\u2010021\u201000457\u20100"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.66.4.45"}],"container-title":["Neuropathology and Applied Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nan.70082","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/nan.70082","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nan.70082","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T03:54:04Z","timestamp":1782186844000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/nan.70082"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,26]]},"references-count":39,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1111\/nan.70082"],"URL":"https:\/\/doi.org\/10.1111\/nan.70082","archive":["Portico"],"relation":{},"ISSN":["0305-1846","1365-2990"],"issn-type":[{"value":"0305-1846","type":"print"},{"value":"1365-2990","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,26]]},"assertion":[{"value":"2025-11-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70082"}}