{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T05:50:22Z","timestamp":1787637022141,"version":"build-2736575974"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Alzheimer\u2019s disease (AD), the most prevalent dementia, is primarily underpinned by the amyloid cascade hypothesis. Passive A\u03b2 immunotherapy effectively reduces cerebral A\u03b2 deposition but is limited by severe side effects, including cerebral amyloid angiopathy (CAA), microhemorrhage, and amyloid-related imaging abnormalities (ARIA). Here, we investigated the efficacy and safety of a novel anti-A\n                      <jats:sub>3\u201310<\/jats:sub>\n                      monoclonal antibody (7B8) in APP\/PS1 double-transgenic mice, with a focus on its impacts on amyloid clearance, neuroinflammation, and blood-brain barrier (BBB) integrity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      7B8 was generated by immunizing mice with A\n                      <jats:sub>3\u201310<\/jats:sub>\n                      -KLH. Six-month-old APP\/PS1 mice were intraperitoneally injected with 7B8 (10 mg\/kg) weekly for 8 doses (7B8 group). Age-matched APP\/PS1 mice treated with IgG and C57BL\/6J mice served as negative and wild-type (WT) controls, respectively. One week after the final injection, behavioral tests were performed, followed by euthanasia for histological (left brain hemisphere) and biochemical (right brain hemisphere) analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Compared with the IgG group, the 7B8 group exhibited significantly reduced cerebral A\u03b2 deposition and improved cognitive function (both\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.05), comparable to the WT group. Notably, in these young 6-month-old APP\/PS1 mice with early-stage amyloid deposition and minimal CAA pathology, 7B8 treatment did not increase microhemorrhage risk relative to the IgG control group (P &amp;gt; 0.05). Furthermore, 7B8 preserved vascular integrity by reducing perivascular A\u03b2\n                      <jats:sub>40<\/jats:sub>\n                      deposition and smooth muscle actin damage, while enhancing endothelial cell fluorescence intensity (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.05). At the molecular level, 7B8 upregulated vascular LRP-1 and BBB tight junction proteins (ZO-1, CLDN-5, Occludin), and downregulated RAGE expression (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.05). It also suppressed microglial and astrocytic activation, reduced levels of IL-6 and cortical TNF-\u03b1, and inhibited the HMGB-1\/RAGE\/NF-\u03baB signaling pathway (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.05), without affecting global TNF-\u03b1 or IL-1\u03b2 levels.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>7B8 effectively alleviates cognitive impairment and clears cerebral and perivascular amyloid deposits in young APP\/PS1 mice with early-stage AD pathology and minimal CAA, with no increased risk of microhemorrhage in this experimental setting. It also protects vascular structure and BBB integrity by inhibiting the HMGB-1\/RAGE\/NF-\u03baB-mediated neuroinflammatory response. Given the limitations of evaluating CAA-related safety in young mice, future studies using mid-aged (12\u201315-month-old) APP\/PS1 mice with prominent CAA will be conducted to fully characterize 7B8\u2019s safety profile. These findings highlight 7B8 as a promising candidate for safe and effective AD immunotherapy, providing new insights into the development of ARIA-minimizing strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1781351","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T05:32:33Z","timestamp":1777527153000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Anti-A\u03b23\u201310 monoclonal antibody 7B8 improves cognitive function and protects the blood-brain barrier in APP\/PS1 mice by regulating the HMGB-1\/RAGE\/NF-\u03baB pathway"],"prefix":"10.3389","volume":"17","author":[{"given":"Jiayu","family":"You","sequence":"first","affiliation":[{"name":"Department of Neurology and Neuroscience, Shenyang First People\u2019s Hospital, Shenyang Brain Institute","place":["Shenyang, Liaoning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianshuo","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology, the Fourth Affiliated Hospital of China Medical University","place":["Shenyang, Liaoning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingqiang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, the Fourth Affiliated Hospital of China Medical University","place":["Shenyang, Liaoning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12694","article-title":"Global estimates on the number of persons across the Alzheimer's disease continuum","volume":"19","author":"Gustavsson","year":"2023","journal-title":"Alzheimers 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