Research Projects

Blood-brain-barrier plays a significant role in the development and progression of Alzheimer’s disease. BBB dysfunction induces the failure of Amyloid beta (Aβ) transport from the brain to the peripheral circulation across the BBB. In Alzheimer’s disease, the accumulation of amyloid beta plaques leads to BBB dysfunction, which increases BBB permeability, allowing serum components to enter the brain from the bloodstream, resulting in progressive synaptic and neuronal dysfunction. However, there are two theories of AD pathology, one is the accumulation of Aβ plaques due to a mutation in the APP gene, and the other is the ‘Tau hypothesis’ caused by the accumulation of insoluble tau proteins, which have undergone different post-translational modifications. This leads to neuroinflammation, oxidative stress and neuronal loss, causing disease progression. Despite serious efforts, the role of the blood-brain-barrier in the development of Alzheimer’s disease, specifically related to Tau protein, remains elusive. We propose to design microfluidic in vitro designs that mimic the BBB and can work as disease modeling and drug screening platforms. The key question we want to ask is: How do Tau protein aggregates (Neurofibrillary tangles - NFT) affect the integrity of the BBB, and what are the consequences for drug transport?. We aim to address this question through our primary objectives in designing two biomimicking microfluidic platforms: the first to investigate the dynamics of Tau (NFT)–BBB interaction, and the second to monitor drug transport through the BBB in the vicinity of NFT. The proposed project has high relevance, as the successful completion of the project can bring in two clinically relevant prototypes. Dementia has emerged as a global health challenge. According to the World Health Organization’s 2022 blueprint for dementia research, an estimated 55.2 million individuals globally are affected. By 2030, the estimated number of people living with dementia will surge to 78 million. Furthermore, the global financial burden associated with medical care, social services, and informal caregiving for those with dementia is expected to exceed US$ 2.8 trillion. In the past decades, most clinical drugs have been discontinued due to limited effectiveness or adverse effects. Detailed understanding of the biology of Alzheimer’s linked to BBB is important in drug design as the tight junctions of BBB significantly influences the transport of drugs. Hence there is critical significance for the project proposed.