Föreläsningar och seminarier What is Life? The Future of Biology Lecture: What is Life (without memory)? Can we use light and sound to treat Alzheimer’s disease?

Biography

Since 2006, Li-Huei Tsai has been the Picower Professor of Neuroscience at MIT and in 2009, she became the director of The Picower Institute for Learning and Memory.

Tsai is a Fellow of the American Association for the Advancement of Science, a Fellow of the National Academy of Inventors, a Member of the National Academy of Medicine, a Member of the American Academy of Arts and Sciences, and an Academician of the Academia Sinica in Taiwan.  She is a recipient of the Mika Salpeter Lifetime Achievement Award, the 2018 Hans Wigzell Research Foundation Science Prize for her research on Alzheimer’s disease, and The Institute of Biomedicine of Seville (IBiS) Distinguished Investigator Award in 2021.  She is currently the Vallee Foundation Visiting Professor at the Karolinska Institute.

Abstract

Tsai’s investigations of Alzheimer’s disease (AD) began with her generation of a severe neurodegeneration mouse model, the inducible CK-p25 mice that exhibits neuroinflammation, neurodegeneration and cognitive impairment.  This model has led to the discovery of a plethora of new targets for therapeutic intervention including chromatin remodeling factors and master regulators of neuroinflammation.  Her lab also employs AI/machine learning methodology to analyze big epigenomic data derived from human brains and animal models, and uses human induced pluripotent stem cells in complex cell cultures to model Alzheimer’s risk genes including APOE4. 

In 2009, through collaboration with Christopher Moore and Karl Deisseroth, investigators in her lab including Marie Carlen and Konstantinos Meletis  employed optogenetics to drive synchronous gamma rhythms in mouse cortex.  To develop a more therapeutically plausible method, her lab teamed up with MIT colleagues Edward Boyden and Emery Brown to discover that external patterned visual stimulation presented at the gamma frequency could also induce gamma rhythms.  Such enhanced gamma rhythms led to reduced AD-related amyloid pathology in mouse models.  Subsequently her team demonstrated that combined visual and auditory stimulation evoked gamma rhythms in many brain regions and improved learning and memory in multiple AD mouse models.

In December 2021, Tsai and team reported in a pilot clinical study that audio and visual gamma sensory stimulation is safe and well tolerated in humans and appears to reduce brain volume loss and enhance brain connectivity in early-stage AD subjects.  She and  Boyden are the scientific co-founders of Cognito Therapeutics which has been conducting larger human clinical trials using gamma sensory stimulation targeting mild to moderate AD subjects.  Encouraging results from Phase II testing  earned the company a “Breakthrough Device” Designation from the United States Food and Drug Administration. The company has since launched a Phase III trial.  To date, multiple laboratories throughout the world have adopted the concept of using non-invasive gamma stimulation to treat various neurological disorders.

In addition to clinical studies, Tsai’s lab continues to investigate the underlying mechanisms mediating the effects of gamma sensory stimulation in the brain. Evidence points to a systemic response among neurons and multiple glial cell types and brain vasculature, indicating that exogenous manipulation of brain rhythms may have disease-altering effects at the cellular and molecular activity.