{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T01:12:30Z","timestamp":1790644350036,"version":"4.1.0"},"reference-count":73,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T00:00:00Z","timestamp":1669766400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      The inositol polyphosphate\u20105\u2010phosphatase D (\n                      <jats:italic>INPP5D<\/jats:italic>\n                      ) gene encodes a dual\u2010specificity phosphatase that can dephosphorylate both phospholipids and phosphoproteins. Single nucleotide polymorphisms in\n                      <jats:italic>INPP5D<\/jats:italic>\n                      impact risk for developing late onset sporadic Alzheimer's disease (LOAD).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      To assess the consequences of inducible\n                      <jats:italic>Inpp5d<\/jats:italic>\n                      knockdown in microglia of APP\n                      <jats:sup>KM670\/671NL<\/jats:sup>\n                      \/PSEN1\n                      <jats:sup>\u0394exon9<\/jats:sup>\n                      (PSAPP) mice, we injected 3\u2010month\u2010old\n                      <jats:italic>\n                        Inpp5d\n                        <jats:sup>fl\/fl<\/jats:sup>\n                        \/Cx3cr1\n                        <jats:sup>CreER\/+<\/jats:sup>\n                      <\/jats:italic>\n                      and\n                      <jats:italic>\n                        PSAPP\/Inpp5d\n                        <jats:sup>fl\/fl<\/jats:sup>\n                        \/Cx3cr1\n                        <jats:sup>CreER\/+<\/jats:sup>\n                      <\/jats:italic>\n                      mice with either tamoxifen (TAM) or corn oil (CO) to induce recombination.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      At age 6 months, we found that the percent area of 6E10\n                      <jats:sup>+<\/jats:sup>\n                      deposits and plaque\u2010associated microglia in\n                      <jats:italic>Inpp5d<\/jats:italic>\n                      knockdown mice were increased compared to controls. Spatial transcriptomics identified a plaque\u2010specific expression profile that was extensively altered by\n                      <jats:italic>Inpp5d<\/jats:italic>\n                      knockdown.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      These results demonstrate that conditional\n                      <jats:italic>Inpp5d<\/jats:italic>\n                      downregulation in the PSAPP mouse increases plaque burden and recruitment of microglia to plaques. Spatial transcriptomics highlighted an extended gene expression signature associated with plaques and identified CST7 (cystatin F) as a novel marker of plaques.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>\n                            <jats:italic>Inpp5d<\/jats:italic>\n                            knockdown increases plaque burden and plaque\u2010associated microglia number.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Spatial transcriptomics identifies an expanded plaque\u2010specific gene expression profile.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Plaque\u2010induced gene expression is altered by\n                            <jats:italic>Inpp5d<\/jats:italic>\n                            knockdown in microglia.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Our plaque\u2010associated gene signature overlaps with human Alzheimer's disease gene networks.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.12821","type":"journal-article","created":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T07:00:20Z","timestamp":1669791620000},"page":"2239-2252","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":71,"title":["Microglial\n                    <i>INPP5D<\/i>\n                    limits plaque formation and glial reactivity in the PSAPP mouse model of Alzheimer's disease"],"prefix":"10.1002","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6817-7388","authenticated-orcid":false,"given":"Emilie L.","family":"Castranio","sequence":"first","affiliation":[{"name":"Department of Neurology Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4378-3685","authenticated-orcid":false,"given":"Philip","family":"Hasel","sequence":"additional","affiliation":[{"name":"Neuroscience Institute NYU Grossman School of Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5748-9666","authenticated-orcid":false,"given":"Jean\u2010Vianney","family":"Haure\u2010Mirande","sequence":"additional","affiliation":[{"name":"Department of Neurology Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angie V.","family":"Ramirez Jimenez","sequence":"additional","affiliation":[{"name":"Department of Neurology Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9510-5611","authenticated-orcid":false,"given":"B. 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