Grant: Project Grant

Alzheimer's disease (AD) is the most common cause of dementia affecting the elderly population in our society. People with AD suffer loss of memory and have trouble making decisions and using language. The disease is caused by two distinct clumps of proteins called neuritic plaques and neurofibrillary tangles formed by amyloid beta peptide and tau proteins, respectively. Abnormal accumulation of these proteins' triggers death of brain cells and subsequent development of disease pathology, but how they do so are not clear. Evidence suggests that tau protein can aggregate with each other, leading to the formation of toxic molecules which contribute to the cell death and spreading of disease pathology in AD brains. In this study, we will use one type of biomolecule called PLGA nanoparticles, which are clinically approved for human use, to determine their ability not only to prevent tau aggregation but also to trigger disassembly of preformed tau aggregates. Additionally, we will test if these nanoparticles can inhibit entry and aggregation of tau in cells grown in petri dish. In parallel, we will determine if these PLGA nanoparticles can reduce AD-related pathology in brain neurons grown in petri dish as well as in animal models displaying AD-related memory loss and pathology. Finally, we will use postmortem AD brain samples and neurons derived from AD patients to determine therapeutic potential of PLGA nanoparticles in the treatment of AD pathology. It is encouraging that PLGA nanoparticles are already clinically approved for the delivery of drugs in various pathological conditions. Thus, results from this study can provide critical information whether PLGA nanoparticles can be safely and rapidly repurposed as a potential treatment for AD patients.