{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T16:03:16Z","timestamp":1790092996400,"version":"4.0.1"},"reference-count":0,"publisher":"Aging and Disease","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Aging Dis"],"abstract":"<jats:p>Alzheimer's disease (AD) is characterized by amyloid-beta (A\u03b2) accumulation, neuroinflammation and cognitive impairment. During AD pathogenesis, A\u03b2 undergoes several post-translational modifications, the most common of which is the isomerization of aspartic acid (isoD7-A\u03b2), a modification that contributes to the disease development. Passive immunization with isoD7-A\u03b2-specific antibodies reduced cognitive impairment and amyloid deposition in 5xFAD mice. However, therapeutic application of anti-A\u03b2 antibodies has important limitations, emphasizing the need for alternative approaches. Here, we evaluated the efficacy of isoD7-A\u03b21-16-targeting immunization compared with A\u03b21-16-targeting immunization on AD pathogenesis in APP\/PS1 mice. Both isoD7-A\u03b21-16 and A\u03b21-16, conjugated with ovalbumin, induced A\u03b21-16 - specific memory B cells and IgG in mice. However, only isoD7-A\u03b21-16 conjugate promoted B cell and IgG response to the neoepitopes on isoD7-A\u03b21-16. In the Y-maze test, only APP\/PS1 mice immunized with isoD7-A\u03b21-16 at 3 months of age retained spatial memory as they aged, in contrast to APP\/PS1 mice immunized with A\u03b21-16 at the same age. Immunization with both isoD7-A\u03b21-16 and A\u03b21-16 significantly reduced amyloid burden, lowered microglial and astrocyte activation. Furthermore, we assessed the effect of immunization in APP\/PS1 mice at a later stage of AD pathogenesis, at 6 months of age. Even at the stage of advanced disease, immunization with isoD7-A\u03b21-16 strongly impeded the formation of amyloid plaques and reduced brain-wide microglial and astrocyte activation, in contrast to immunization with A\u03b21-16. Our results indicate the promise of targeting isoD7-A\u03b2 for active AD immunotherapy, both for preventing the development of the pathology at its early stage and for ceasing the advanced AD pathogenesis.<\/jats:p>","DOI":"10.14336\/ad.2026.0695","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T15:25:55Z","timestamp":1790090755000},"source":"Crossref","is-referenced-by-count":0,"title":["Targeting isoD7 Neoepitope in A\u03b2 for Alzheimer's Disease Immunotherapy"],"prefix":"10.14336","member":"5462","published-online":{"date-parts":[[2026]]},"container-title":["Aging and Disease"],"original-title":[],"deposited":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T15:25:56Z","timestamp":1790090756000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.aginganddisease.org\/EN\/10.14336\/AD.2026.0695"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":0,"URL":"https:\/\/doi.org\/10.14336\/ad.2026.0695","relation":{},"ISSN":["2152-5250"],"issn-type":[{"value":"2152-5250","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026]]}}}