Does Pathology in Locus Coeruleus Trigger AD?
The locus coeruleus (LC) of the brain is important for sleep and memory, but it’s unclear if accumulation of tau in its neurons is an early sign of Alzheimer’s disease. By studying the electrical activity of LC neurons in mice, we will determine if tau prevents LC to function normally and causes sleep and memory problems. In addition, we will manipulate the activity of the LC neurons in order to restore its function and reverse sleep and memory impairment.
Tau, one of the hallmark pathologies of AD, accumulates in the locus coeruleus of 20-year-old healthy adults, and yet, its consequences remain unknown. To mimic tau accumulation in the LC, we will extract tau from human AD brains and inject it into the LC of mice. We will then monitor sleep and test memory determine if tau impacts sleep prior to the onset of AD-like cognitive symptoms. A major innovation of this project is to be able to predict the onset of AD. The study pioneers the use of multi-region electrodes to probe brain regions involved in sleep and memory combined with machine learning approach to predict early symptoms of AD. Additionally, the project aims to reverse LC dysfunction using optogenetic tools.
The results of this study will inform and help predict if sleep disturbances in young adults are important predictors Alzheimer's disease.
About the Researcher
I am an Assistant Professor in the Department of Pathology and Cell Biology at the Taub Institute at Columbia University Irving Medical Center. I received my PhD in Neurobiology at Freie Universität Berlin, Germany. I worked on honeybee olfaction and sleep under the guidance of Dr. Randolf Menzel. My postdoctoral training was in Dr. Eric Kandel’s (Nobel laureate, 2000) laboratory at Columbia University where I worked on understanding the mechanism underlying spatial memory in the hippocampus of an enhanced memory mouse model- HCN1. To understand the function of the entorhinal cortex in the HCN1 mice, I collaborated with Drs. Edvard Moser and May-Britt Moser (Nobel laureates, 2014) at NTNU, Norway. For the past five years I have focused on understanding how the entorhinal cortex-hippocampal circuit is affected in Alzheimer’s disease mice using in vivo electrophysiology, optogenetics and chemogenetics. One of the major goals of my lab is to study regions of the brain most vulnerable to pathology.
My father was an electrical engineer and an artist in fixing broken gadgets no matter how old. As a child I was inspired to open up his broken electrical gadgets and stare at them in wonder. While I understood nothing about the working of the equipment, I wished I knew how to fix them. That curiosity to learn the mechanics and fix a broken system was what led me to my life’s calling to be a scientist.
I majored in biology and a course in human anatomy made me realize how little we knew about the workings of the human brain. After a year studying neuropharmacology- a fascinating world of mind-altering drugs- I was convinced that I wanted to be a neuroscientist. I obtained doctoral and post-doctoral training in neuroscience wherein I studied the mechanism of memory formation. Having pursued years of research on how memories are formed, my interest was piqued to delve into the science of memory loss. I now study dementia.
My career follows the dream of the little boy who yearns to understand the intricate workings of dysfunctional gadgets and hoping to fix them – now it’s broken brains.
I thank BrightFocus Foundation for the award that will allow me to understand Alzheimer’s disease better.
First published on: May 6, 2020
Last modified on: May 28, 2020