Integrating in-vitro neurovascular organoids and computational models for understanding Alzheimer's disease onset mechanism and progression
Description
Alzheimer’s disease (AD), known as the leading cause of dementia, currently lacks an early detection procedure and treatment. One in three older Americans die with AD dementia; 6.9million Americans aged 65 and older are living with Alzheimer's dementia. This number is projected to double by 2060, including younger-onset dementia leading to AD. This research proposal seeks to provide answers to: What is the role of neuronal electrical circuits and activities in the onset and progression of AD? We hypothesize that oxidative stress initiates and accelerates AD, with the objective of developing a multidisciplinary platform that facilitates decoding the interaction of neurodegenerative-oxidative biomarkers in AD model; utilizing induced pluripotent stem cell techniques to develop in-vitro 3D mini brain organs in the form of neurovascular organoid models, and high-density microelectrode arrays to measure electrophysiological biomarkers of the developed models in real-time for understanding and tracking the AD progression. We will conduct assays for oxidative stress biomarkers (glutathione, superoxide dismutase, among others), integrating machine learning algorithms and HDF5 data format to analyze large datasets from our experimental procedures. Finally, we will evaluate the specificity and sensitivity (validation/correlation) of our findings for early diagnosis and therapeutic purposes in relation to AD unraveling.