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Since current therapies provide predominantly symptomatic relief without halting disease progression, the development of robust disease\u2010modifying interventions remains a critical unmet medical need. Here, we discuss the most recent advances in active immunisation strategies targeting pathological A\u03b2 and Tau species and their potential to meaningfully modify the AD trajectory. Early vaccines such as AN1792 demonstrated proof\u2010of\u2010concept but were limited by T\u2010cell\u2010mediated adverse events. Second\u2010generation approaches, including CAD106, UB\u2010311, ABvac40 and ACI\u201024, improved safety and immunogenicity through short peptide fragments and liposomal formulations. Next\u2010generation platforms such as MultiTEP and SupraAntigen, alongside nucleic acid\u2010based vaccines, further optimise immune responses, overcoming immunosenescence and selectively targeting toxic oligomers while sparing physiological proteins. Tau\u2010targeted vaccines, including AADvac1, ACI\u201035 and AV\u20101980R, show selective reduction of pathological Tau with promising preclinical and early clinical results. Combined A\u03b2\/Tau vaccination demonstrates synergistic effects in preclinical models, supporting multi\u2010target strategies. Future directions focus on preventive vaccination, alternative delivery routes and biomarker\u2010driven personalisation, collectively supporting a shift towards integrated multi\u2010target immunotherapy capable of modulating AD pathology and potentially altering its long\u2010term clinical course.<\/jats:p>","DOI":"10.1002\/eji.70250","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T06:36:53Z","timestamp":1787035013000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Active Vaccination Strategies for Alzheimer's Disease: An Expanded Review"],"prefix":"10.1002","volume":"56","author":[{"given":"Antonella","family":"Comitato","sequence":"first","affiliation":[{"name":"Scientific Directorate Azienda USL\u2010IRCCS di Reggio Emilia  Reggio Emilia 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