Low-Dimensional Nanomaterials in Alzheimer's Disease: Current Applications

Alzheimer's Disease (AD) is a common neurodegenerative disorder (NDD) driven by multifaceted pathologies, including β-amyloid (Aβ) aggregation, tau protein hyperphosphorylation, oxidative stress, metal ion dyshomeostasis, and neuroinflammation. Current therapeutic strategies remain limited by insufficient Blood-Brain Barrier (BBB) penetration, singletarget approaches, and inefficacy against nanoscale pathological aggregates. This review highlights the emerging potential of low-dimensional nanomaterials (LDNMs) as multi-target therapeutic platforms for AD.

We systematically evaluate zero-dimensional (0D), one-dimensional (1D), and twodimensional (2D) nanostructures and establish a "nano-nano" interaction paradigm that demonstrates how LDNMs interact with AD core pathological factors. Supporting tables summarize experimental data quantifying the effects of LDNMs on Aβ and tau pathologies, oxidative stress, metal ion homeostasis, neuroinflammation, and the delivery of BBB-penetrant drugs.

LDNMs exhibit significant potential in mitigating core AD pathologies. They effectively inhibit Aβ aggregation and tau hyperphosphorylation, attenuate oxidative damage, restore metal ion homeostasis, reduce neuroinflammatory activity, and enable targeted drug delivery to the brain.

The multi-target functionality of LDNMs overcomes major limitations of single-target therapies. Their nanoscale dimensions and modifiable surfaces enable synergistic interactions with pathological factors, offering a holistic intervention strategy. Limitations and translational challenges are discussed for future research directions for clinical application.

This review links the structure and drug loading of LDNMs to multi-targeted efficacy against core AD pathology. It establishes a mechanistic connection between nanomaterial size and multi-pathway efficacy that transcends the limitations of single-target strategies. Moreover, it also provides a comprehensive framework for designing LDNMs-based nanotherapeutics, highlighting their potential as multi-target platforms for AD therapy.