Current strategies for the development of fluorescence-based molecular probes for visualizing the enzymes and proteins associated with Alzheimer’s disease

Abstract

One of the most prevalent forms of dementia is Alzheimer's disease (AD) which causes severe memory impairment within humans. As such, research into the early diagnosis of AD is essential to help treatment, which has led to significant advances in fluorescence imaging. Unfortunately, modern medicine and biology place increasingly strict requirements for fluorescent probes. Therefore, over recent years, researchers have taken strides to develop novel fluorescent molecular probes, with properties suitable for modern clinical applications, including low phototoxicity, weak background interference, deep tissue penetration, enhanced specificity, strong binding affinity, and suitable permeability through the blood–brain barrier (BBB). From these recent research results, many novel concepts for molecular design and fluorescence techniques have emerged. Herein, we present strategies towards the development of probes capable of meeting the advanced clinical requirements. As part of this review, we will summarize the characteristic enzymes and proteins involved in AD progression, including Amyloid-β, β-secretase, tau protein, monoamine oxidases, and methionine sulfoxide reductase. Then, we will evaluate some of the early probes and summarize the recent advancements made in the design of probes suitable for clinical applications, from which several strategies have emerged, such as increasing permeability to the blood–brain barrier, enhancing specificity by boosting binding affinity, and improving optical properties for in vivo imaging, etc. Then to conclude current strategies for early stage diagnosis of AD will be presented, and the opportunities as well as the remaining challenges will be outlined.