Exosome-Mediated Delivery of Amyloid Beta Modulators: A Potential Therapeutic Strategy for Alzheimer's Disease

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the deposition of amyloid-beta (Aβ) plaques and tau protein abnormalities, disrupting synaptic function and causing progressive cognitive decline. However, significant efforts in research are still hampered by current treatments, which are limited by poor penetration of the BBB and non-specific effects. Recent developments in nanotechnology and drug delivery have found exosomes as innovative carriers targeting Aβ. They have identified a novel approach to treating the underlying pathology of AD. Exosomes are naturally occurring extracellular vesicles with several unique advantages. They are biocompatible, can cross the BBB, and can be engineered to deliver therapeutic agents with precision. These agents range from small interfering RNA (siRNA), peptides, or drugs designed to either inhibit Aβ aggregation, enhance its clearance, or regulate the genes involved in its production. Among these agents, neural-derived exosomes offer great promise as they naturally attract neuronal tissue and, therefore, increase the specificity of the treatment. In preclinical studies, such therapies have proven encouraging by demonstrating reduced Aβ accumulation, a decrease in neuroinflammation, and cognitive improvement in models of AD. However, translation into clinical application faces some challenges, such as development of scalable methods of exosome production, drug loading efficiency, stability, and safety upon administration. The present review takes an outlook toward the growing area of targeting Aβ pathology via exosomes with potential benefits, recent breakthroughs, and open challenges. Harnessed therapy from exosomes can create groundbreaking-therapies in treating AD that hope for millions to come out from this devastator disease.

Keywords: Alzheimer’s disease; Amyloid plague; Amyloid precursor protein; Amyloid-beta; Exosomes; Extravesicular vesicles.