Active Immunization Targeting Amyloid β for the Treatment of Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is the most prevalent neurodegenerative condition worldwide. It is characterized by the formation of amyloid beta (Aβ) plaques in the brain and by the accumulation of neurofibrillary tangles; the disease is marked by cognitive decline and memory impairment over time. Although cholinesterase inhibitors and <sc>N</sc>-methyl-<sc>D</sc>-aspartate receptor antagonists have been used to relieve symptoms, immunotherapies to treat the disease itself by targeting removal of amyloid are now beginning to be applied clinically. However, methods that allow the control of AD symptoms and that would require only a few clinical follow-ups are often preferred by patients. Thus, active immunization, or vaccination, against Aβ and tau is still being explored as a possible therapeutic intervention.

SUMMARY: This review aims to describe ongoing and discontinued immunization trials to treat AD. We conducted a comprehensive review of the literature to analyze the current status of vaccinations for AD. We examined and summarized the studies and clinical trials that explored the efficacy, safety, and challenges associated with this therapeutic approach.

KEY MESSAGES: This review highlights the potential for vaccination development to treat AD, including its efficacy, associated complications, and limitations. Much progress has been made over the past 2 decades, but challenges remain. Immunization is a promising avenue for treating or preventing symptomatic AD, offering potential benefits beyond symptomatic relief. Because challenges such as immunogenicity and safety profiles need to be addressed, further research and development are necessary to meet the growing demand for patient-acceptable, effective AD treatments.