Nanoparticle-mediated approaches for Alzheimer's disease pathogenesis, diagnosis, and therapeutics

Abstract

Alzheimer's disease (AD) is an irreversible and progressive neurodegenerative disorder manifested by memory loss and cognitive impairment. Deposition of the amyloid β plaques has been identified as the most common AD pathology; however, the excessive accumulation of phosphorylated or total tau proteins, reactive oxygen species, and higher acetylcholinesterase activity are also strongly associated with Alzheimer's dementia. Several therapeutic approaches targeting these pathogenic mechanisms have failed in clinical or preclinical trials, partly due to the limited bioavailability, poor cell, and blood-brain barrier penetration, and low drug half-life of current regimens. The nanoparticles (NPs)-mediated drug delivery systems improve drug solubility and bioavailability, thus renders as superior alternatives. Moreover, NPs-mediated approaches facilitate multiple drug loading and targeted drug delivery, thereby increasing drug efficacy. However, certain NPs can cause acute toxicity damaging cellular and tissue architecture, therefore, NP material should be carefully selected. In this review, we summarize the recent NPs-mediated studies that exploit various pathologic mechanisms of AD by labeling, identifying, and treating the affected brain pathologies. The disadvantages of the select NP-based deliveries and the future aspects will also be discussed.

Keywords: Acetylcholine; Alzheimer’s disease; Amyloid β; Nanoparticles; ROS; Tau protein.