Antibody-based nanoparticles in Alzheimer's disease: Innovations in diagnosis and therapy

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by accumulation of amyloid-β (Aβ) plaque, tangles of tau neurofibres, chronic neuroinflammation, and dysfunction of the blood brain barrier (BBB). Monoclonal antibodies targeting Aβ and tau have focused disease-modifying potential, but their clinical impact is limited in brain penetration, immunogenicity, amyloid-related imaging abnormalities (ARIA), high treatment costs, and the need for repeated intravenous administration. These limitations has lead to discover in antibody-based nanoparticle platforms as advanced delivery and diagnosis.

This review aims to evaluate antibody-based nanoparticles as emerging tools for the diagnosis and treatment of AD, focusing on nanoparticle design, antibody conjugation strategies, mechanisms of BBB transport, immune modulation, and current translational challenges.

Recent preclinical studies reflects that antibody-functionalized nanoparticles can improve target specificity, enhance BBB transport by receptor-mediated and adsorptive transcytosis, and modulate neuroinflammatory responses by microglial Fc-receptor engagement. Advances in nanoparticle materials including gold, magnetic iron oxide, polymeric, and lipid-based systems has applications in both therapy and molecular imaging using MRI and PET. Critical barriers including nanoparticle instability, immune clearance, antibody denaturation after conjugation, long-term toxicity, manufacturing scalability, and regulatory uncertainty for hybrid biologic nanomaterial products exist.

Antibody-based nanoparticles represent promising but still evolving platform for precision diagnostics and targeted therapy in AD. While preclinical evidence is encouraging, successful clinical translation depends on standardized manufacturing, comprehensive safety evaluation, and well-designed trials. Future efforts focus on theranostic systems, multi-target antibody platforms addressing pathology, and regulatory frameworks supporting scalable and reproducible nanoparticle-based interventions.