Zinc‐Based Nanocomposites for Alzheimer's Therapy: Restoring Metal Homeostasis and Inhibiting Neurotoxic Protein Aggregation

ABSTRACT Alzheimer's disease (AD) is a complex neurodegenerative condition characterized by oxidative stress, tau hyperphosphorylation, amyloid‐β (Aβ) buildup, and synaptic dysfunction. Developing effective treatments for AD is hampered by the extremely selective blood–brain barrier (BBB), which prevents most therapeutic medicines from entering the central nervous system. The BBB uses carefully controlled transport mechanisms to preserve cerebral homeostasis. It is composed of endothelial cells connected by tight junctions and supported by astrocytes and pericytes. BBB rupture, on the other hand, causes increasing neuronal damage, elevated neuroinflammation, and decreased Aβ clearance in AD. Zinc‐based nanocomposites have gained attention recently as possible carriers for resolving issues related to the BBB. Enzymatic activity, antioxidant defence, and synaptic signalling are all significantly impacted by zinc, an essential trace mineral. Zinc oxide nanoparticles, Zn–EGCG complexes, and Zn‐doped polymeric systems are examples of engineered zinc nanostructures that exhibit innate neuroprotective properties, efficient drug delivery, and BBB penetration. In experimental models of AD, these multipurpose nanocarriers promote neuronal survival, inhibit Aβ aggregation, restore zinc homeostasis, and control oxidative stress. The BBB's construction and function, pathogenic changes in AD, and new approaches based on nanoparticles for targeted brain delivery are the main topics of this review. Zinc‐based nanocomposites are highlighted as dual‐purpose therapeutic and delivery systems, highlighting their potential as next‐generation therapies for Alzheimer's disease and associated neurodegenerative diseases.