Rescuing Impaired Memory in Alzheimer's Disease Using Reactivation of Brain Network Activity

Kei Igarashi, PhD
University of California, Irvine (Irvine, CA)
Year Awarded:
2019
Grant Duration:
July 1, 2019 to June 30, 2022
Disease:
Alzheimer's Disease
Award Amount:
$300,000
Grant Reference ID:
A2019380S
Award Type:
Standard
Award Region:
US Northwestern
Kei Igarashi, PhD

Rescuing Memory Using Cell-type Specific Reactivation of Memory Network Activity

Summary

You remember where you put your car keys after work. And you remember how to drive to your work place, of course. These abilities rely on a type of memory called spatial memory. If you lose spatial memory, you will be in trouble when you look for your keys the next day or drive all over town looking for your work place. 60% of Alzheimer’s patients lose spatial memory and show wandering behavior.

In 2014, Drs. John O’Keefe, Edvard Moser and May-Britt Moser were awarded the Nobel Prize in Medicine for their discovery of the brain cells responsible for spatial memory, called “place cells” and “grid cells”. These cells are part of the brain's memory circuit and are critical for spatial memory in healthy rodents and humans. However, it is still unclear what happens to these cells in AD patients. Are place cells and grid cells lost in Alzheimer’s? If so, is it possible to restore the spatial memory of AD patients by reactivating place cells and grid cells? We will use cutting-edge electrophysiological and circuit manipulation techniques to answer these questions in animal models of AD.

Details

In the previous decades, AD research has been mainly focusing on identifying proteins and neuronal cells involved in pathogenesis. Brain network mechanisms that cause memory impairments in AD have not been well investigated. However, basic systems neuroscience has advanced dramatically since 2000. We will leverage this knowledge and technical improvements systems neuroscience to understand AD pathogenesis. We will identify which types of cells in the brain's memory circuitry degrade in AD, and will identify why such deterioration of brain cells causes memory impairment. Our studies will significantly advance our understanding of the brain network mechanisms of memory impairment in AD, and will help identify target networks to prevent or slow the progression of disease. These studies are expected to help us develop effective procedures for brain stimulation as a powerful tool to preserve (or improve) memory function to slow the rate of memory decline in AD patients.

About the Researcher

Dr. Kei Igarashi received his PhD in systems neuroscience from the University of Tokyo School of Medicine. Dr. Igarashi then moved to Norway in 2009 for his postdoctoral fellowship to work in the lab of Drs. Edvard Moser and May-Britt Moser at the Norwegian University of Science and Technology. There, Dr. Igarashi published seminal works showing how two brain regions, the entorhinal cortex and hippocampus, interact to form memory. These works, published in prestigious scientific journals including Nature and Neuron (Igarashi et al., Nature 2014; Li, Igarashi et al., Neuron 2015), contributed to Drs. Edvard Moser and May-Britt Moser’s Nobel prize in 2014. In 2016, Dr. Igarashi moved to University of California, Irvine, to lead a research group on AD and mechanisms of memory. His lab has a longstanding record of innovation. At UC Irvine, Dr. Igarashi is currently an assistant professor. In addition to the strong support from BrightFocus Foundation, Dr. Igarashi’s work is also supported by awards from Brain Research Foundation, Japanese Government, Donors Cure Foundation, and National Institute of Health.

Personal Story

I started my career as a basic neuroscientist studying brain circuit mechanisms related to the sense of smell and then memory. While I was studying on basic research during my PhD, my grandmother, Yuriko, started to show symptoms of Alzheimer’s disease. She was 78 at that time.

One day, she said “I put my purse here, but it’s gone! You stole my purse!”. Imagine how sad if your dearest grandma starts to doubt you. She was starting to lose her spatial memory and could not remember where she put it. We brought her to a doctor, even though she strongly refused. At that time, she was not diagnosed as Alzheimer’s, but as we anticipated, she was diagnosed a year later.

There were no drugs approved for Alzheimer’s disease in Japan at that time. All we could do for her is to have fun together; to prevent her brain from worsening. We often brought her to short trips (picture 1).

These efforts were, however, in vain. She started to lose personal recognition at 84. I was the one of first people she could not recognize. She called me “teacher”. “Hello teacher, you have a beautiful baby” she said, when I visited her at her senior residence to show off my first baby. She loved my baby, but could not recognize that the baby was her first great-grandchild.

I went out from the country to study more after that and was only able to visit once a year. She started to use diapers. Every time I visited her, she did not recognize me. I was asking myself, "Am I visiting her for her sake, or for my own sake?" At 89, she lost recognition of my mother, her own daughter. Now she was all alone.

She passed away at 93. Alzheimer’s disease completely killed her personality, long before she passed away.

I could not do anything for her, even though I AM A MEMORY RESEARCHER. This frustration is keep driving me to fight Alzheimer’s disease.

Alzheimer’s disease is a disease that we need to cure.

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