Active immunization: A novel therapeutic strategy for treating Alzheimer's disease

Alzheimer's disease is an age-dependent chronic neurodegenerative disorder characterized by progressive and chronic neurodegenerative disorder leading to cognitive decline and dementia. FDA-approved drugs only treat Alzheimer's disease, not cure it. Monoclonal antibodies (passive immunotherapy) target the pathological forms of amyloid β, improve cognitive function, and slow down the progression of Alzheimer's disease. Moreover, inconsistent therapeutic outcomes with the use of monoclonal antibodies led the doubts about their therapeutic effectiveness and the amyloid β cascade hypothesis. Recently, active immunotherapy has shown efficacy by producing antibodies against disease-related amyloid β and multiple phosphorylation sites of tau. CAD 106, a first second-generation vaccine, showed no incidence of amyloid β-specific T-cell response, meningoencephalitis, and CNS inflammation. However, no vaccine has been licensed for clinical practice. In this review, we described different hypotheses explaining the development of Alzheimer's disease, available therapy, and their limitations, and different active immunotherapeutic agents, their mechanisms, preclinical and clinical outcomes, challenges in the development, and future perspectives.