{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:36:23Z","timestamp":1786977383147,"version":"build-2736575974"},"reference-count":80,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T00:00:00Z","timestamp":1745452800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chronic Diseases and Translational Medicine"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Monoclonal antibodies (mAbs) have made significant progress in the treatment of Alzheimer's disease (AD). However, mAbs are associated with adverse effects, including Amyloid\u2010Related Imaging Abnormality (ARIA), which manifests as edema or effusion (ARIA\u2010E) and hemorrhage (ARIA\u2010H). The mechanisms behind these effects are not yet fully understood. Moreover, spontaneous ARIA has been insufficiently explored, and mAb therapies, particularly lecanemab, have mainly focused on patients with the\n                    <jats:italic>APOE\u2010\u03b54<\/jats:italic>\n                    allele carrier. This review aims to address this gap by examining the mechanisms of spontaneous ARIA, ARIA induced by mAbs, and the influence of genetic variants on ARIA development. The autoantibody\u2010A\u03b2\u2010mediated immune response targets excessive A\u03b2 deposits, increasing immune activity through microglial reactivity. The heightened immune response, driven by A\u03b2 accumulation in blood vessels, promotes angiopathy and inflammation, potentially contributing to spontaneous ARIA. The\n                    <jats:italic>APOE\u2010\u03b54<\/jats:italic>\n                    allele carrier is more strongly associated with ARIA\u2010E because it redistributes A\u03b2 deposition from the brain to blood vessels, influencing microglial reactivity. The redistribution enhances vascular integrity and reduces the risk of ARIA\u2010H. However, it also increases the likelihood of ARIA\u2010E due to A\u03b2 accumulation in the vasculature, triggering inflammation. In contrast, the development of ARIA\u2010H is linked to increased\n                    <jats:italic>TREM2<\/jats:italic>\n                    expression and microglial reactivity, leading to impaired vascular integrity and disrupted matrix remodeling, which worsens the condition. Additionally, the adverse effects of mAbs may extend beyond the\n                    <jats:italic>APOE\u2010\u03b54<\/jats:italic>\n                    allele, possibly impacting other genetic variants involved in microglial reactivity, A\u03b2 redistribution, and vascular integrity.\n                  <\/jats:p>","DOI":"10.1002\/cdt3.70006","type":"journal-article","created":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T02:09:17Z","timestamp":1745546957000},"page":"186-196","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Amyloid\u2010Related Imaging Abnormality (ARIA) Beyond the APOE\u2010\u03b54 Allele"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0927-4919","authenticated-orcid":false,"given":"Valentinus","family":"Besin","sequence":"first","affiliation":[{"name":"Faculty of Medicine University of Surabaya Surabaya 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