Smart Fluorophores for Early Detection, Diagnostics to Therapeutics of Alzheimer’s Disease
Alzheimer’s disease (AD) has posed tremendous social and economic burden worldwide. As the elderly population and their life expectancy increase, the number of people suffered from AD is anticipated to increase to more than 131 million by 2050, according to Alzheimer’s Disease International. There are long-awaited unmet challenges in the aspects of early detection, diagnostics and therapeutics for such devastating AD. Detection and quantification of AD biomarkers can be informative and dispensable for pre-clinical AD, even before the presence of amyloid deposition visible by PET imaging, as early detection of at-risk subjects allows preventive and delaying measures for the progression to AD. Development of a powerful imaging technique with molecular sensitivity for AD diagnosis is crucial to monitoring the disease’s progression and understanding the complex disease processes as well as the evaluation of effectiveness of potential AD drugs. AD has a multifactorial pathoetiological origin. Current therapeutic approaches only offer limited remedies with only transient symptomatic benefits to patients, but without halting or reversing the progression of the disease. Development of multi-target drugs that acts on two or more specific etiological targets of the disease may offer a better pathway towards the development of much needed disease-modifying therapeutics.
To tackle the unmet early detection, diagnostic and therapeutic challenges for AD. Based on our cumulative results and established structure-properties relationship findings, a class of novel versatile and multifunctional non-toxic and neuroprotective, blood brain barrier permeable as well as Aβ oligomer-selective fluorescence molecules with strong binding affinity and binding-induced fluorescence enhancement will be designed, synthesized and characterized for the applications of early detection, diagnosis, and therapy for AD. We propose herein to (1) develop sensitive detection and accurate quantification of the plasma Aβ oligomers as AD biomarkers that could allow population-wide screening and early pre-clinical diagnosis of AD; (2) develop Aβ peptide-specific magnetic resonance imaging contrast agent as a powerful tool to detect, diagnose and monitor the disease status and progression; and (3) develop and/or identify multi-target, non-toxic and blood-brain barrier permeable small-molecule compounds that serve as potential drug candidates for the prevention and amelioration of AD.
Candidate with a good chemistry degree.