According to the Alzheimer’s Association, over 5.4 million Americans suffer from Alzheimer’s disease, and the cost of caring for AD is estimated to total $236 billion in 2016. Abnormal accumulation of amyloid beta, a peptide produced in neuronal cells, plays a key role in both early and late forms of AD, leading to the neuronal injury and synaptic dysfunction. Despite the debate about the role of amyloid beta in AD pathogenesis, substantial research supports the hypothesis that an imbalance between production and clearance of amyloid beta causes excess amyloid beta accumulation in the CNS, even as a very early, often initiating factor in AD. Recent work also showed that while increased amyloid beta production seems to be a central mechanism in rare, familial cases of early-onset AD due to mutations in amyloid precursor protein (APP) and presenilin (PSEN), reduced amyloid beta clearance appears to be the primary mechanism involved the commonly occurring form of late-onset sporadic AD. With no current treatment for AD, there is a large unmet need for the development of new therapeutics including enhanced amyloid beta clearance that improves the prognosis for AD patients.

We develop a neurovascular-unit-on-a-chip (NVUoC) device to study the role of microglia and astrocytes in neurodegenerative diseases including Alzheimer's. Our current project is to engineer biomimetic nanomaterials for targeted delivery of ion channel inhibitors and for enhanced clearance of amyloid beta. We evaluate these materials using our NVUoC and validate our findings in the 5xFAD mouse model.

We are in close collaboration with Prof. Allan Levey, Prof. Srikant Rangaraju, and Prof. Malu Tansey at Emory University School of Medicine.