Project 458943

Alzheimer's disease (AD) is an incurable neurodegenerative disease that is projected to affect 150 million people by 2050. Researchers believe that the memory loss observed in AD is due to a pathological overactivity of the brain that ultimately leads to its malfunction. Despite what is understand about AD, potential treatments often fail in clinical trials. These failures are often attributed to the fact that many treatments use rodents or cells as their modelling system for a human, three-dimensional cerebral disease. Treatments will often appear effective at the rodent- or cellular-level, but this does not translate to clinical success and can even worsen a patient's memory loss. The field of neurodegenerative disease is greatly lacking a modeling system that more accurately represents features and symptoms of an adult AD patient's brain. However, recent advances in cerebral organoid technology may be the answer to this problem. Cerebral organoids (COs) are mini lab-grown brains that have been observed to capture many aspects of brain development. Notably, normal COs show coordinated, electrical brain activity similar to preterm infants and AD in cerebral organoids (AD-COs) appear to progress and worsen in a similar fashion to real adult patients. Therefore, COs could be used to understand how an overactive brain can lead to AD and memory loss. We will create AD-COs and use our lab's optogenetic tools to turn on and off specific neurons in the COs, thereby manipulating and examining its neural activity. By doing this, we can better understand how neural activity might be affected when memories are formed, accessed and subsequently forgotten in AD. Ultimately, developing this platform for modeling human memory and using optogenetics to manipulate its neural activity will be critical for our understanding of the mechanism between hyperactivity and AD progression, thus allowing us to better design effective AD therapies.