{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T13:10:39Z","timestamp":1793970639934,"version":"4.8.0"},"reference-count":58,"publisher":"Society for Neuroscience","issue":"11","license":[{"start":{"date-parts":[[2013,9,13]],"date-time":"2013-09-13T00:00:00Z","timestamp":1379030400000},"content-version":"vor","delay-in-days":184,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2013,3,13]]},"abstract":"<jats:p>\n                    Neuroinflammation is an important component of Alzheimer's disease (AD) pathogenesis and has been implicated in neurodegeneration. Interleukin-1 (IL-1), a potent inflammatory cytokine in the CNS, is chronically upregulated in human AD and believed to serve as part of a vicious inflammatory cycle that drives AD pathology. To further understand the role of IL-1\u03b2 in AD pathogenesis, we used an inducible model of sustained IL-1\u03b2 overexpression (IL-1\u03b2\n                    <jats:sup>XAT<\/jats:sup>\n                    ) developed in our laboratory. The triple transgenic mouse model of AD, which develops plaques and tangles later in its life cycle, was bred with IL-1\u03b2\n                    <jats:sup>XAT<\/jats:sup>\n                    mice, and effects of IL-1\u03b2 overexpression on AD pathology were assessed in F1 progeny. After 1 and 3 months of transgene expression, we found robust increases in tau phosphorylation despite an \u223c70\u201380% reduction in amyloid load and fourfold to sixfold increase in plaque-associated microglia, as well as evidence of greater microglial activation at the site of inflammation. We also found evidence of increased p38 mitogen-activated protein kinase and glycogen synthase kinase-3\u03b2 activity, which are believed to contribute to tau phosphorylation. Thus, neuroinflammation regulates amyloid and tau pathology in opposing ways, suggesting that it provides a link between amyloid accumulation and changes in tau and raising concerns about the use of immunomodulatory therapies in AD.\n                  <\/jats:p>","DOI":"10.1523\/jneurosci.4361-12.2013","type":"journal-article","created":{"date-parts":[[2013,3,13]],"date-time":"2013-03-13T12:54:54Z","timestamp":1363179294000},"page":"5053-5064","source":"Crossref","is-referenced-by-count":373,"title":["Sustained Interleukin-1\u03b2 Overexpression Exacerbates Tau Pathology Despite Reduced Amyloid Burden in an Alzheimer's Mouse Model"],"prefix":"10.1523","volume":"33","author":[{"given":"Simantini","family":"Ghosh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Solomon S.","family":"Shaftel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanos","family":"Kyrkanides","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank M.","family":"LaFerla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Olschowka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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