Award Title: A Fluorophore-nanoparticle Composite Designed for the Early Stage Diagnosis of Alzheimer's Disease
Funder: The Academy of Medical Sciences

Abstract: The seeming unstoppable rise of Alzheimer's disease (AD) worldwide represents a significant and challenging public health problem. However, early diagnosis of AD can enable improved disease treatments and alleviate significant associated symptoms, thereby, significantly improving a patients outlook and quality of life. Amyloid β-protein (Aβ-protein) is a particularly important biomarker for AD. The pathological features of Alzheimer's disease in the brain are characterized by the deposition of amyloid β-protein in the hippocampus and cortex of the brain, as well as neurofibrillary tangles (NFTs) due to hyperphosphorylation of Tau protein. With this research we plan to develop a near-infrared (NIR) fluorescence imaging tools for the early diagnosis of AD. A nanocarrier approach will be used to selectively release in a controlled manner a NIR imaging probe. The probe will be selectively released from the nanocarrier upon action of enzymes (such as acetylcholinesterase) found in the AD microenvironment. When compared with current diagnostic tools such as single electron emission computed tomography (SPECT) and Positron emission computed tomography (PET) imaging, our approach does not require expensive equipment and can achieve high sensitivity and selectivity. Additionally, in comparison with other optical imaging approaches, the fluorescence of the NIR imaging probe will only be turned on when activated by the AD microenvironment/enzymes, facilitating both high sensitivity and selectivity during deep tissue imaging of the brain. We anticipate that our approach will enable the development of clinically relevant tools for the early diagnosis of AD.

Lay Abstract: With the advent of aging population, the incidence of neurodegenerative diseases has increased year on year. Among them, Alzheimer's disease (AD) has become one of the major diseases that endanger public health with almost 350 million people worldwide being affected. AD is currently a disease that cannot be prevented and cured, and the clinical drug test failure rate is as high as 90%. While current medications cannot cure AD, they can help alleviate the symptoms and therefore an early diagnosis can significantly benefit the patient’s quality of life. Clinical findings indicate that a certain type of protein is deposited in the brain during the development of AD. Therefore, we aim to image that protein in order to aid the early diagnosis and real-time monitoring of the progression of AD. This project aims to develop a new near-infrared (NIR) imaging probe whose fluorescence can be triggered by the AD microenvironment and enzymes in order to investigate the effects of the deposited protein. Compared with current diagnostic tools, our approach does not require expensive equipment and can achieve high selectivity and sensitivity. We anticipate that our approach will enable the development of clinically relevant tools for the early diagnosis of AD.

Research Activity Codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health Categories: NEUROLOGICAL