Vaccines as Potential Therapeutic Strategies for Alzheimer’s Disease: A Systematic Review (Preprint)

UNSTRUCTURED Abstract Alzheimer’s disease (AD), a progressive neurodegenerative disorder, poses significant challenges due to its complex pathophysiology and limited therapeutic options. Recent research has explored vaccines as innovative therapeutic strategies to target amyloid-beta (Aβ) plaques and tau protein aggregates, key pathological hallmarks of AD. This systematic review aims to evaluate the efficacy, safety, and immunological mechanisms of vaccine-based approaches for AD treatment. Following PRISMA guidelines, we conducted a comprehensive search of peer-reviewed literature from databases including PubMed, Scopus, and Web of Science, focusing on preclinical and clinical studies published up to October 2025. Studies were included if they investigated active or passive immunization targeting Aβ or tau in AD models or human trials. Data were synthesized to assess vaccine-induced immune responses, cognitive outcomes, and adverse effects. Preliminary findings suggest that vaccines can reduce Aβ and tau pathology in preclinical models, with some clinical trials reporting modest cognitive benefits; however, challenges such as neuroinflammation and variable efficacy persist. This review highlights the potential of vaccines as a therapeutic avenue for AD, while underscoring the need for further research to optimize immunogenicity, safety, and clinical translation. These insights contribute to the growing field of AD immunotherapy and inform future therapeutic development.