{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:11:11Z","timestamp":1790633471725,"version":"4.1.0"},"reference-count":70,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004200","name":"Olle Engkvists Stiftelse","doi-asserted-by":"publisher","award":["213\u20100295"],"award-info":[{"award-number":["213\u20100295"]}],"id":[{"id":"10.13039\/501100004200","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021594","name":"Demensfonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100021594","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Cellular senescence, a state of irreversible cell cycle arrest, plays a key role in neurodegenerative diseases, including Alzheimer's disease (AD). While senescent cells are emerging as potential therapeutic targets, the dynamics of their occurrence over time and the specific cell types most affected by AD are still not well understood. This study investigates age\u2010 and pathology\u2010dependent changes in senescence markers, specifically p16, p21, and p53, using the amyloidogenic\n                    <jats:italic>App<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>NL\u2010G\u2010F<\/jats:italic>\n                    <\/jats:sup>\n                    knock\u2010in AD mouse model. Female\n                    <jats:italic>App<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>NL\u2010G\u2010F<\/jats:italic>\n                    <\/jats:sup>\n                    and wild\u2010type (WT) mice were evaluated at 4, 12, and 24\u2009months of age to capture disease progression changes from early to advanced AD stages. Immunofluorescence and qPCR were used to quantify p16, p21, and p53 expressions. Senescence\u2010associated \u03b2\u2010galactosidase (SA\u2010\u03b2\u2010Gal) activity, IL\u20101\u03b2 and IL\u20106 levels, and CD68\u2010p21 colocalization were assessed. At 4\u2009months\u2010of\u2010age, only p21 levels in astrocytes differ between genotypes. By 12\u2009months,\n                    <jats:italic>App<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>NL\u2010G\u2010F<\/jats:italic>\n                    <\/jats:sup>\n                    mice exhibited increased p16 and p21 expression in glial cells, along with elevated SA\u2010\u03b2\u2010Gal activity. IL\u20101\u03b2 level increased in the cortex and hippocampus, while IL\u20106 only in the hippocampus. Most CD68\u2010positive microglia co\u2010expressed p21 in both hippocampus (73%) and cortex (82%), indicating a prevalent senescent phenotype among reactive microglia. p16 and p21 changes became more pronounced at 24\u2009months. p53 expression followed a distinct pattern, increasing in astrocytes at 12\u2009months and in microglia by 24\u2009months. Neurons showed no genotype\u2010dependent differences. These findings reveal a progressive, amyloid\u2010linked glial senescence response, supporting the\n                    <jats:italic>App<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>NL\u2010G\u2010F<\/jats:italic>\n                    <\/jats:sup>\n                    model as a reliable platform for evaluating senotherapeutic strategies in AD.\n                  <\/jats:p>","DOI":"10.1111\/acel.70478","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T12:48:17Z","timestamp":1776170897000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Cell Type\u2010Specific Expression of p16, p21, and p53 Reveals Age\u2010Dependent Glial Senescence in the\n                    <i>\n                      App\n                      <sup>NL\u2010G\u2010F<\/sup>\n                    <\/i>\n                    Mouse Model of Alzheimer's Disease"],"prefix":"10.1111","volume":"25","author":[{"given":"Eileen Mac","family":"Sweeney","sequence":"first","affiliation":[{"name":"Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society Karolinska Institutet  Solna Sweden"},{"name":"Division of Pharmacology, Department of Molecular and Translational Medicine University of Brescia  Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9161-3475","authenticated-orcid":false,"given":"Giulia","family":"Abate","sequence":"additional","affiliation":[{"name":"Division of Pharmacology, Department of Molecular and Translational Medicine University of Brescia  Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bjorn R. V.","family":"Bakker","sequence":"additional","affiliation":[{"name":"Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society Karolinska Institutet  Solna Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8862-2896","authenticated-orcid":false,"given":"Andrea","family":"Mastinu","sequence":"additional","affiliation":[{"name":"Division of Pharmacology, Department of Molecular and Translational Medicine University of Brescia  Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ylenia","family":"Lai","sequence":"additional","affiliation":[{"name":"Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society Karolinska Institutet  Solna Sweden"},{"name":"Department of Biological Sciences University of Cagliari, Cittadella Universitaria di Monserrato  Monserrato Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Uberti","sequence":"additional","affiliation":[{"name":"Division of Pharmacology, Department of Molecular and Translational Medicine University of Brescia  Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Nilsson","sequence":"additional","affiliation":[{"name":"Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society Karolinska Institutet  Solna Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7000-7556","authenticated-orcid":false,"given":"Simone","family":"Tambaro","sequence":"additional","affiliation":[{"name":"Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society Karolinska Institutet  Solna 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