Project 462336

Recent innovations in neuroscience have led to the development of human-derived 'mini-brains', also known as cerebral organoids. These self-organizing, three-dimensional clusters of human brain tissue can grow to 2-3 mm in diameter, and accurately mimic many aspects of human brain development and physiology. Since they are derived from a patient, either their skin or blood, these mini-brains have the same genetic make-up as the patient. When derived from patients with neurological disease, derivative neurons in these mini-brains exhibit many of the pathological features of the disease. Thus, cerebral organoids are a valuable tool for disease research. In this project, we explore a new avenue for characterizing how the human brain changes in an Alzheimer's disease (AD) state using a novel set of tools that can look at how the chemistry and metabolism of the brain differ in those individuals with disease versus healthy individuals. We can then correlate this information to the cellular makeup, genetics, and function of these brain cells, which will provide new clues as to how genes influence the brain environment, its function and chemistry. Cerebral organoids will be derived from human participants who are undergoing healthy brain aging and show no signs of dementia, and from individuals who have been diagnosed with AD. We will then study these patient-derived brain organoids using our integrated platform to characterize biological and chemical changes that accompany healthy brain aging versus AD. The proposed research will identify imaging biomarkers of AD that will be translatable to human patients in the clinic. It will also establish a unique platform for understanding the mechanisms of healthy brain aging and for testing novel therapies against AD.