{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:24:58Z","timestamp":1790612698227,"version":"4.1.0"},"reference-count":70,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["AG061708"],"award-info":[{"award-number":["AG061708"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Neuronal degeneration and immune cell activation occur early in Alzheimer's disease (AD), but the responsible molecules remain undetermined. While exogenous amyloid beta oligomers (A\u03b2Os) induce neuronal death and gliosis, the role of endogenous A\u03b2Os is less defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Brain sections from 1\u2010 to 12\u2010month\u2010old 5xFAD mice were immunolabeled for A\u03b2Os, activated glia, phosphorylated transactive response DNA\u2010binding protein 43 kDa (pTDP\u201043), and other AD markers. Neuropathology was analyzed following 60\u2010day oral treatment with NU\u20109, a small\u2010molecule A\u03b2O inhibitor.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      By 8\u00a0weeks, A\u03b2Os accumulated in the subiculum alongside early reactive astrocytes and activated microglia. Clinical\u2010stage antibody ACU193 detected A\u03b2Os in early\u2010stage degenerating neurons, while NU4\u2010labeled denser deposits in late\u2010stage degenerating neurons. ACU193\n                      <jats:sup>+<\/jats:sup>\n                      A\u03b2Os accumulated on reactive astrocyte surfaces, which also contained pTDP\u201043,\u00a0and later emerged inside activated microglia. NU\u20109 reduced astrocyte\u2010associated ACU193\n                      <jats:sup>+\u00a0<\/jats:sup>\n                      A\u03b2Os, pTDP\u201043, and markedly diminished glial fibrillary acidic protein.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>\n                      These findings demonstrate in vivo efficacy of NU\u20109 and support targeting ACU193\n                      <jats:sup>+\u00a0<\/jats:sup>\n                      A\u03b2Os to mitigate AD progression.\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                            ACU193\n                            <jats:sup>+<\/jats:sup>\n                            A\u03b2Os accumulated as puncta in neurons at an early stage of degeneration, while NU4\n                            <jats:sup>+<\/jats:sup>\n                            A\u03b2Os appeared as dense deposits only in late\u2010stage degenerating neurons.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            The onset and progression of ACU193\n                            <jats:sup>+<\/jats:sup>\n                            A\u03b2Os paralleled activated microglia and reactive astrocytes.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            ACU193\n                            <jats:sup>+<\/jats:sup>\n                            A\u03b2Os significantly increased on reactive astrocyte surfaces, as NU4\n                            <jats:sup>+<\/jats:sup>\n                            A\u03b2Os accumulated in halos around Thio\u2010S\n                            <jats:sup>+<\/jats:sup>\n                            plaque cores.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>In older mice, the ACU193 signal decreased on astrocytes and was found inside activated microglia.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Sixty\u2010day oral NU\u20109 treatment significantly reduced astrocyte ACU193\n                            <jats:sup>+<\/jats:sup>\n                            A\u03b2Os and markedly decreased reactive astrogliosis.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70968","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T12:01:37Z","timestamp":1766059297000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Identification of a glia\u2010associated amyloid \u03b2 oligomer subtype and the rescue from reactive astrogliosis by inhibitor NU\u20109"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-4125-4029","authenticated-orcid":false,"given":"Daniel L.","family":"Kranz","sequence":"first","affiliation":[{"name":"Department of Neurobiology Northwestern University  Evanston Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"de Leon Velez","sequence":"additional","affiliation":[{"name":"Department of Neurobiology Northwestern University  Evanston Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emel","family":"Ulupinar","sequence":"additional","affiliation":[{"name":"Department of Neurology, Feinberg School of Medicine Northwestern University  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. Hande","family":"Ozdinler","sequence":"additional","affiliation":[{"name":"Department of Neurology, Feinberg School of Medicine Northwestern University  Chicago Illinois USA"},{"name":"Chemistry of Life Processes Institute Northwestern University  Evanston Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard B.","family":"Silverman","sequence":"additional","affiliation":[{"name":"Chemistry of Life Processes Institute Northwestern University  Evanston Illinois USA"},{"name":"Department of Chemistry Northwestern University Evanston Illinois USA"},{"name":"Department of Molecular Biosciences, Center for Developmental Therapeutics Northwestern University Evanston Illinois USA"},{"name":"Department of Pharmacology, Feinberg School of Medicine Northwestern University  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William L.","family":"Klein","sequence":"additional","affiliation":[{"name":"Department of Neurobiology Northwestern University  Evanston Illinois USA"},{"name":"Department of Neurology, Feinberg School of Medicine Northwestern University  Chicago Illinois USA"},{"name":"Department of Chemistry Northwestern University Evanston Illinois 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