Immunotherapeutic Advances in Alzheimer's Disease: The Convergence of Vaccinology and Nanoscience

Curr Alzheimer Res. 2026 May 22. doi: 10.2174/0115672050415433251106050120. Online ahead of print.

Abstract

Amyloid-beta plaques and neurofibrillary tangles promote neuronal dysfunction and cognitive loss, the hallmarks of Alzheimer's disease (AD), a serious global health concern. Current medications offer only symptomatic alleviation, emphasizing the critical need for disease-- modifying therapy. This study was performed using MeSH term search by using keywords, like "Alzheimer's Disease", "AD", "Vaccines", "Nanoformulations", "Amyloid-Beta (Aβ) Vaccines", "lecanemab", "Tau protein Vaccines", "AADvac1", "Clinical trials". The development of vaccines and methods based on nanotechnology is the primary focal point of this review, which explores immunotherapeutic approaches. Active and passive immunization are used in the development of AD vaccines to target tau and amyloid-beta pathology. While passive immunization involves the direct delivery of pre-formed antibodies, active immunization aims to stimulate the patient's own immune system to produce antibodies in response to the antigen. The necessity for effective drug delivery across the blood-brain barrier (BBB), safety issues, and inconsistent efficacy are some of the difficulties facing vaccine delivery strategies. Nanotechnology can overcome the drawbacks of traditional treatments by providing novel approaches for gene therapy, RNA-based interventions, and targeted medication administration. Immunization approaches offer multiple benefits, including regulated and targeted antigen release, as well as stabilizing the vaccine antigens. Therapeutic drugs can be delivered across the BBB, and genes linked to AD can be modulated by nanoparticles and liposomes that resemble exosomes. Current developments, including the incorporation of short Aβ epitopes, liposomal formulations, conformational mimotopes, and virus-- like particles (VLPs), have markedly enhanced vaccine tolerability. Effective AD treatments depend on combination medications, individualized approaches, and ongoing research into crossing the BBB and improving the safety and effectiveness of vaccines.

Keywords: Alzheimer’s disease vaccine; amyloid-beta; clinical trials.; immunotherapy; nanotechnology; tau-protein.