{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:07:51Z","timestamp":1791925671218,"version":"4.3.4"},"reference-count":25,"publisher":"Rockefeller University Press","issue":"12","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2012,11,19]]},"abstract":"<jats:p>The apolipoprotein E (APOE) \u03b54 allele is the strongest genetic risk factor for Alzheimer\u2019s disease (AD). The influence of apoE on amyloid \u03b2 (A\u03b2) accumulation may be the major mechanism by which apoE affects AD. ApoE interacts with A\u03b2 and facilitates A\u03b2 fibrillogenesis in vitro. In addition, apoE is one of the protein components in plaques. We hypothesized that certain anti-apoE antibodies, similar to certain anti-A\u03b2 antibodies, may have antiamyloidogenic effects by binding to apoE in the plaques and activating microglia-mediated amyloid clearance. To test this hypothesis, we developed several monoclonal anti-apoE antibodies. Among them, we administered HJ6.3 antibody intraperitoneally to 4-mo-old male APPswe\/PS1\u0394E9 mice weekly for 14 wk. HJ6.3 dramatically decreased amyloid deposition by 60\u201380% and significantly reduced insoluble A\u03b240 and A\u03b242 levels. Short-term treatment with HJ6.3 resulted in strong changes in microglial responses around A\u03b2 plaques. Collectively, these results suggest that anti-apoE immunization may represent a novel AD therapeutic strategy and that other proteins involved in A\u03b2 binding and aggregation might also be a target for immunotherapy. Our data also have important broader implications for other amyloidosis. Immunotherapy to proteins tightly associated with misfolded proteins might open up a new treatment option for many protein misfolding diseases.<\/jats:p>","DOI":"10.1084\/jem.20121274","type":"journal-article","created":{"date-parts":[[2012,11,6]],"date-time":"2012-11-06T05:15:07Z","timestamp":1352178907000},"page":"2149-2156","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":151,"title":["Anti-apoE immunotherapy inhibits amyloid accumulation in a transgenic mouse model of A\u03b2 amyloidosis"],"prefix":"10.1084","volume":"209","author":[{"given":"Jungsu","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Neurology 1 , 2 , and the, 3"},{"name":"Hope Center for Neurological Disorders 1 , 2 , and the, 3"},{"name":"Knight Alzheimer\u2019s Disease Research Center, Washington University School of Medicine, Saint Louis, MO 63110 1 , 2 , and the, 3"},{"name":"Department of Neurology 1 , 2 , and the, 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