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AD patients frequently experience recurrent systemic inflammatory insults from comorbid conditions, which act as\u00a0\u201csecondary\u2010hits\u201d believed to worsen cognitive decline. The impact of these secondary insults \u00a0on astrocyte\u2010mediated neurovascular regulation remains unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      We applied intravital two\u2010photon microscopy to longitudinally investigate astrocytic Ca\n                      <jats:sup>2<\/jats:sup>\n                      <jats:sup>+<\/jats:sup>\n                      dynamics and functional hyperemia during sensory stimulation in APP\/PS1dE9 mice before and during secondary lipopolysaccharide (LPS)\u2010induced systemic inflammation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      AD mice exhibited diminished stimulation\u2010evoked astrocytic Ca\n                      <jats:sup>2<\/jats:sup>\n                      <jats:sup>+<\/jats:sup>\n                      activity, while functional hyperemia remained largely preserved. LPS further suppressed astrocytic Ca\n                      <jats:sup>2<\/jats:sup>\n                      <jats:sup>+<\/jats:sup>\n                      responses and produced temporally specific vascular alterations, with AD and wild\u2010type mice following divergent inflammatory trajectories.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>\n                      Our findings provide the first in vivo longitudinal characterization of how secondary systemic inflammation disrupts astrocyte\u2010mediated neurovascular regulation. The selective vulnerability of astrocytic Ca\n                      <jats:sup>2<\/jats:sup>\n                      <jats:sup>+<\/jats:sup>\n                      signaling relative to vascular output implicates recurrent inflammatory insults as a clinically relevant contributor to neurovascular dysfunction in preclinical AD.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71607","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T11:00:18Z","timestamp":1784804418000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prolonged systemic inflammation worsens impairments to astrocyte Ca\n                    <sup>2+<\/sup>\n                    and functional hyperemia in Alzheimer's disease"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7661-5456","authenticated-orcid":false,"given":"Chang","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Bioengineering Northeastern University  Boston Massachusetts USA"},{"name":"Department of Biomedical Engineering Southern University of Science and Technology  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimia","family":"Sakha","sequence":"additional","affiliation":[{"name":"Department of Bioengineering Northeastern University  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime","family":"Anton","sequence":"additional","affiliation":[{"name":"Department of Bioengineering Northeastern University  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Cardenas\u2010Rivera","sequence":"additional","affiliation":[{"name":"Department of Bioengineering Northeastern University  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad A.","family":"Yaseen","sequence":"additional","affiliation":[{"name":"Department of Bioengineering Northeastern University  Boston Massachusetts 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