NEXT GENERATION DIAGNOSTIC AGENTS FOR ALZHEIMER’S DISEASE

Alzheimer’s disease (AD) is the most common neurodegenerative disease and the sixth leading cause of death in United States. More than 6 million people are presently diagnosed with AD in the US, and the number is expected to reach 14 million by 2050. To date there is no disease-modifying treatment for AD and its diagnosis with high accuracy requires a detailed post-mortem examination of the brain. Therefore, there is a huge unmet need to develop diagnostic agents for early detection of AD. 

While the main neuropathological hallmark of AD is the deposition of amyloid plaques comprising the amyloid beta (Aβ) peptide, new therapeutic targets also include the phosphorylated tau (p-tau) aggregation, as well as reactive oxygen species generation, neuroinflammation, and oxidative stress. Significant efforts have focused on developing accurate biomarker imaging and diagnostic approaches via cerebrospinal fluid protein analysis and positron emission tomography (PET) imaging; however, these methods can be invasive and expensive. Magnetic resonance imaging (MRI) has emerged as a potential complement to CSF and PET analyses. 

Over the past several years Professor Mirica has developed a series of multifunctional compounds that exhibit high affinity for both insoluble and soluble Aβ aggregates, can act as antioxidants and anti-inflammatory agents, and importantly can cross the blood-brain barrier (BBB) and specifically bind to Aβ species in vivo. In addition, he has developed a BBB-permeable Cu-64 PET imaging agent that is stable in vivo and allowed the successful PET imaging of amyloid plaques in the brains of AD transgenic mice vs. those of wild type (WT) mice. During his CAS appointment, he plans to develop BBB-permeable MRI contrast agents and dual PET/MRI agents for early AD diagnosis. He will take advantage of his extensive expertise in coordination chemistry and in developing BBB-permeable multifunctional chelators to generate multimodal imaging agents for in vivo applications.