CNLM Director Awarded $3.8 million to identify biomarkers for Alzheimer’s Disease

Irvine, Calif., Oct. 23, 2017 — With $3.8 million in support from the National Institute on Aging, University of California, Irvine neurobiologists are working to identify the early indicators of dementia in older adults as disease-related brain plaques accumulate but before symptoms can be observed.

The researchers are developing sophisticated methods using brain imaging technology to understand the mechanisms of Alzheimer’s disease and predict its onset before any outward manifestations. If successful, their work will pave the way for effective preventive treatments that will substantially increase quality of life for patients and reduce the burden on families and the healthcare system.

“Cognitive decline is a significant public health concern as the population over the age of 60 continues to grow sharply,” said Michael Yassa, Chancellor’s Fellow and associate professor of neurobiology & behavior and director of the Center for the Neurobiology of Learning & Memory at UCI. “We will be faced with $50 trillion in Medicare costs as baby boomers age, making this effort to determine biomarkers for Alzheimer’s disease all the more significant.”

He added that the five-year study aims to pinpoint factors leading to cognitive decline in the presence and absence of beta-amyloid proteins, the hallmark brain plaques associated with Alzheimer’s disease. Yassa will lead a team in testing and monitoring 150 adults between the ages of 60 and 85 who have no symptoms of dementia but may have a family history of it.

Ultrahigh-resolution MRI scans will be used to gauge brain structure and function, and florbetapir PET scans will measure amyloid plaques, while highly sensitive cognitive examinations will detect subtle memory deficits. Participants’ cognitive health will be followed for several years to determine whether the test results can reliably predict outcomes. It is hoped that this research will shed light on the mechanisms of Alzheimer’s disease during the pre-symptomatic phase. Successful completion will allow Yassa and his colleagues to provide guidelines for designing future clinical trials to prevent or delay the onset of Alzheimer’s.

The study investigators will work closely with the UCI Alzheimer’s Disease Research Center to identify potential subjects and monitor them longitudinally. The team also includes Daniel Gillen, professor and chair of statistics, and Joshua Grill, associate professor of psychiatry & human behavior and associate director of the ADRC.

For more information, visit the Yassa lab. Individuals interested in participating should contact study coordinator Liv McMillan at yassalabresearch@uci.edu.

About the University of California, Irvine: Founded in 1965, UCI is the youngest member of the prestigious Association of American Universities. The campus has produced three Nobel laureates and is known for its academic achievement, premier research, innovation and anteater mascot. Led by Chancellor Howard Gillman, UCI has more than 30,000 students and offers 192 degree programs. It’s located in one of the world’s safest and most economically vibrant communities and is Orange County’s second-largest employer, contributing $5 billion annually to the local economy. For more on UCI, visit www.uci.edu.

Media access: Radio programs/stations may, for a fee, use an on-campus ISDN line to interview UCI faculty and experts, subject to availability and university approval. For more UCI news, visit news.uci.edu. Additional resources for journalists may be found at communications.uci.edu/for-journalists.

CNLM Community Advisory Board Member Marcia Milchiker awarded Marian Bergeson Award!

Congratulations to CNLM Community Advisory Board Member Marcia Milchiker who received the Marian Bergeson Award by the Orange County School Boards Association for her dedication to promoting and enhancing public education through leadership and community service. We are grateful for Marcia’s longtime involvement with the Center for the Neurobiology of Learning and Memory and for her dedication to public education! Click here to learn more about Marcia Milchiker and the Marian Bergeson Award.

Marcia Milchiker with Dr. Wendy Suzuki at the Practical Neuroscience for Everyday Life event earlier this year!

 

Calling all international memory researchers!

We are pleased to announce that we have partnered with SciTechEdit International to offer support to foreign, non-native English-speaking scientists! SciTechEdit is sponsoring a travel award in the amount of US$1,500 to support one foreign, non-native English-speaking scientist to travel to and participate in the 2018 International Conference on Learning and Memory (LEARNMEM2018). In addition, SciTechEdit is offering a 20% discount (use promotional code CNLM2018) on Comprehensive Editing services applied to all conference materials (abstracts, posters, talks) and abstract editing at no charge. 

Click here to apply to the SciTechEdit International Travel Fellowship

Click here to learn more about how SciTechEdit International can help you prepare and polish your submission!

Click here to submit an abstract to the 2018 International Conference on Learning and Memory

About SciTechEdit International: SciTechEdit International LLC was founded by Karin Coleman-Mesches and Michael Mesches in 1997 in response to the rapidly growing global need for clear science communication. Both Karin and Michael are alumni of the CNLM, having worked with Dr. Jim McGaugh. Since founding SciTechEdit International, Karin and Michael have edited and supervised the editing of scientific communications, including manuscripts, grants, letters, and posters, for thousands of scientists in over 65 countries. We are thrilled to partner with them on LEARNMEM2018 and appreciate their continued support!

Announcing the BrightFocus Travel Fellowship

We are very excited to announce that the CNLM has partnered with BrightFocus Foundation to offer three Travel Fellowships in the amount of $1,500 each to support students, postdoctoral fellows and faculty who study Alzheimer’s Disease and who will be participating in the 2018 International Conference on Learning and Memory. These Fellowships are supported by a generous grant from the BrightFocus Foundation.

Eligibility:
To apply, you must be a graduate student, postdoctoral fellow or early career faculty member (within 7 years of terminal degree) who will participate in #LEARNMEM2018 by presenting a poster, open paper talk, lightning talk or symposium talk focusing on Alzheimer’s disease. You must submit a proposal in order to be eligible to apply. Your proposal must be accepted to receive an award. Women, underrepresented minorities, and individuals with disabilities are strongly encouraged to apply.

About BrightFocus Foundation:
BrightFocus is a nonprofit organization that supports research to end Alzheimer’s disease, macular degeneration and glaucoma. BrightFocus is at the forefront of brain and eye health, advancing early-stage, investigator-initiated research around the world. BrightFocus also provides educational materials to people affected by or interested in these diseases, empowering them to take action for themselves and others. Click here to learn more about BrightFocus Foundation.

Click here to apply to the BrightFocus Travel Fellowship

Click here for more information about the 2018 International Conference on Learning and Memory (#LEARNMEM2018)

Navigating brain oscillations and Alzheimer’s disease

Space, the final frontier. Uncharted and unexplored, it remains a mystery to us. But aside from the common cliché – apologies to all Trekkies – space is much more than the enigmatic celestial void we contemplate with wonder and awe. It is everything around us, from our personal space to traversing the planet. Navigating successfully around space is essential to our survival as a species. Some may be better than others. There’s even a gender difference, but I’ll let you guess what it is. As we get older, all of us begin to struggle a little with navigating around new as well as familiar spaces. But for a patient with Alzheimer’s disease, this ability can be severely compromised. Enter Kei Igarashi, assistant professor of Anatomy and Neurobiology and Fellow of the Center for the Neurobiology of Learning and Memory (CNLM) at the University of California, Irvine. His work is making strides in understanding how spatial navigation and spatial memory mechanisms deteriorate in Alzheimer’s disease, potentially paving the way to improved diagnosis and treatment.

I arrived at Igarashi’s newly established lab in Irvine Hall on the medical school campus ready to pepper him with questions about his most recent paper. He welcomed me into his no frills office looking out onto Irvine’s expanse of undeveloped desert.

On one side stood a wooden chair etched with the University of California letters. “I bought this for 30 bucks!” he commented with pride. On the other side stood a bookcase where one book in particular was placed prominently in front – a pristine copy of The Cognitive Neuroscience of Memory by Howard Eichenbaum, a memory pioneer who had passed away suddenly only a few days before our interview. Eichenbaum visited the Irvine CNLM just a few months before and Igarashi made sure to get his copy of the book signed by the distinguished author. “His early studies on olfaction informed my work a great deal. Such a tragic loss to us all…” he soberly remarked.

Kei Igarashi with 2014 Nobel Laureates Edvard and May-Britt Moser and John O’Keefe

He asked me to sit down on a cushioned chair next to his desk, as I pulled out my camera, pen, and notepad. Igarashi arrived at Irvine in the spring of 2016 after completing a highly coveted postdoctoral fellowship with Edvard and May-Britt Moser. The Mosers were awarded the 2014 Nobel Prize in Physiology or Medicine, an award they shared with University College London’s John O’Keefe for their collective discoveries related to the brain mechanisms of spatial navigation. The Mosers direct the Kavli Institute for Systems Neuroscience in Trondheim, Norway. “I could not have asked for better mentors in fundamental science”, he said.

Since arriving at Irvine, Igarashi’s lab has focused on making new inroads into understanding the role of brain oscillations in spatial processing and how these mechanisms are disrupted in Alzheimer’s disease. Spatial navigation involves a set of interconnected circuits nestled in regions deep in the brain, the hippocampus and the entorhinal cortex. The same two regions are among the earliest sites to deteriorate in Alzheimer’s. A coincidence? Likely not. Igarashi is studying this intricate system in detail to identify why it fails.

His lab is recording electrical activity directly from these regions in a novel Alzheimer’s mouse model. The amyloid precursor protein (APP) knock-in model developed by Japanese researchers in 2014, he explained, offers several advantages over transgenic models. This particular model exhibits typical age-related pathology without overproduction of other APP fragments. His findings, published in June of this year, show impairments in the synchrony or coupling of brain waves in these mice. In the normal brain, two different types of brain waves (gamma and theta) synchronize to allow for information transfer from one brain region to another. In the Alzheimer’s mouse, however, gamma oscillations in the entorhinal cortex were impaired.

It was Igarashi’s postdoctoral advisors, the Mosers, who first identified cells in the entorhinal cortex that represent space using a grid pattern (dubbed grid cells). Disruption of the gamma rhythm in the same region could be a possible mechanism for spatial navigation deficits in Alzheimer’s patients. Next, he intends to stimulate the region to determine if the gamma rhythm can be restored. He hopes to accomplish these experiments in the coming months.

Just a synapse away from the entorhinal cortex is another region that is of particular interest to Igarashi. The piriform cortex, the olfactory center in the brain, has direct and privileged access to the entorhinal-hippocampal memory system. All other senses must funnel through the thalamus, traditionally thought to be a relay station (although admittedly it’s more complicated). Olfactory information, however, passes directly to the memory centers of the brain. Igarashi has his eye on this system as well, one that is known to be vulnerable in the early stages of Alzheimer’s disease. Using olfactory tasks with precisely timed odor delivery, he hopes to use a combination of electrophysiological recordings and optogenetics to better understand how this system operates and what features may be compromised in Alzheimer’s.

We walked across the hall to his lab where he took me on a quick tour. Immediately visible were two large computer monitors showing raw traces from the electrodes connected to his physiological recording equipment. Around the lab he had organized a surgical station, a T-shaped maze for behavioral tests in rodents, as well as an olfactory chamber. We then sat at his fabrication station, complete with tools and gadgets for building electrodes and machining electrical components.

“When you’re setting up a lab, no one gives you a shopping list,” he shrugged his shoulders. It was clear that he rose to the challenge quickly and set up his lab with state-of-the-art equipment. “And then of course, some things you have to make”, he demonstrated to me how to make a tetrode – four wires twisted around each other.

I marveled at the simplicity and asked “what does it do?” He laughed, “Everything!” He explained that this simple technology transformed the field by allowing investigators to identify individual cells firing by recording electrical activity in their vicinity. The tetrode was invented by another CNLM Fellow, distinguished professor Bruce McNaughton, one of the key reasons why Igarashi was motivated to come to Irvine. “It’s remarkable to be at the same institution with a pioneer like Bruce.”

As I watched him work the forceps deliberately and carefully under the microscope, I couldn’t help but notice the precision and fine motor skill needed for such work. I asked if this came naturally or took years of practice. “Both” he said, “but I played with Legos quite a bit as a kid.” I suspect it took a bit more than Legos to acquire these skills. Despite having students and postdoctoral fellows in the lab, Igarashi still spends considerable amounts of time in the lab himself, doing experiments, setting up rigs, building tetrodes, testing animals, and teaching his growing team how to use these techniques to address the scientific questions at hand.

Igarashi’s work on spatial processing in Alzheimer’s disease is clearly poised to transform the field and is gaining steady support. Most recently, he received a highly competitive seed grant to support his innovative work from the Brain Research Foundation, a nonprofit supporting neuroscience research. The first of many, he hopes. We hope so too.

Uncharted and unexplored as it may be, work by Igarashi and others stands to make the fundamental and translational neuroscience of space a little less of a mystery.

Click here to learn more about Dr. Igarashi’s research group.

BY: Manuella Yassa

2017 CNLM Award Recipients

The CNLM presents several highly competitive end-of-the-academic-year awards. Awardees are chosen through a selection process by a special committee appointed by the Director. Awardees may receive each award only once. The purpose, criteria and eligibility requirements for each award are available here. This year we presented seven $1,000 awards.

Here are the 2017 CNLM Award Recipients:

Carol Becker McGaugh Award
Ivan Shu (Advisor: Dr. Wood)

Friends of the CNLM Award 
Navid Ghaffari (Advisors: Dr. McGaugh and Dr. Yassa)

Roger W. Russell Award in the Neurobiology of Learning and Memory
Jacky Au
Ryan Lim

John W. Haycock Memorial Graduate Student Travel Award
Maria Montchal

Renée Harwick Advanced Graduate Student Award
Megan Curran
Matthew Mahavongtrakul

We are grateful for the generous support of the Friends of the CNLM, the McGaugh family, the Russell family, the Haycock family and Dr. Renée Harwick for making these awards possible. 

Left to right: Navid Ghaffari, Ryan Lim, Maria Montchal, Megan Curran, Jacky Au, Ivan Shu, Matthew Mahavongtrakul, Michael Yassa

Physical Exercise and Brain Health

On March 2nd, 2017, the CNLM partnered with the UCI Exercise Medicine and Sport Sciences Initiative (EMSSI) to host an international scientific symposium and forum on Physical Exercise and Brain Health where world-renowned scholars shared disocervies on the impact of exercise on brain health and disease and discussed the state of the field and path forward. Speakers emphasized the ability of physical exercise to improve brain function and plasticity, particularly in memory and executive function. They also discussed the need for large-scale studies, the impact of even mild interventions, developing individualized exercise prescriptions, and public policy related to healthy lifestyles and disease prevention. The speakers are now collaborating on a joint commentary highlighting the recommendations from this landmark symposium.


Left to right: James Hicks, Mark Mattson, Carl Cotman, Wendy Suzuki, Laura Baker, Kirk Erickson, Michelle Carlson, Art Kramer, Michael Yassa (missing Henriette van Praag)

Speakers:

Dr. Kirk Erickson, University of Pittsburgh
Dr. Michelle Carlson, Johns Hopkins University
Dr. Henriette van Praag, National Institute on Aging
Dr. Mark Mattson, National Institute on Aging
Dr. Laura Baker, Wake Forest University
Dr. Carl Cotman, University of California, Irvine
Dr. Wendy Suzuki, New York University

Keynote:

Dr. Arthur Kramer, Northeastern University

 

 

 

 

From the CNLM Spring 2017 Newsletter. Click here to read more. 

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CNLM Fellow Dr. Georg F. Striedter publishes field’s leading textbook

Striedter_CoverStudents in Professor Georg Striedter’s Advanced Neurobiology course were pleasantly surprised at the beginning of the term when they learned the textbook they would be using was written by their own instructor! Neurobiology: A Functional Approach introduces students to the concepts of neurobiology in a unique way. It considers the whole organism and the problems that the brain helps the organism solve. Striedter’s background as an evolutionary biologist no doubt had a big role to play in his approach to writing the book. A gifted storyteller, Striedter is passionate about connecting with students and challenging their thinking at the same time. His approach has clearly been effective as the feedback for both the book and his course has been overwhelmingly positive. One reviewer likened it to a classic novel that is also full of deep knowledge of neuroscience. The book also comes loaded with features that enhance learning. “The exercises between the sections tested my knowledge of the bigger picture and helped me to connect concepts,” says Erik Navarro, undergraduate in Striedter’s class. Writing the field’s new leading text is by no means an easy feat. Unlike writing research papers which are reviewed and published with some frequency, writing a scholarly textbook is a long and challenging road that can be an exercise in delayed gratification. Striedter remarks that working with a book publisher can also be a challenge in its own way. There are always compromises on both sides. In the end, it was clearly well worth the effort. This is Striedter’s second book and he is already working on his third. Congratulations, Professor Striedter.

From the Spring 2017 CNLM NeuroTimes. Click here to download full newsletter. 

McGaugh-Gerard Lectureship

A tribute to world-class scholarship and a friendship dating back to UCI’s inception

The CNLM and the Ayala School of Biological Sciences proudly announce the establishment of the McGaugh Gerard Endowed Lecture on Learning and Memory. The lectures will be free to the public and are intended to encourage public education, scientific discourse and exposure to world class science. This lectureship was made possible by the generous support of two gifts totaling $260,000 from Dr. James L. McGaugh and the family trust of the late Dr. Ralph W. Gerard. Drs. McGaugh and Gerard were friends and colleagues who shared a mutual respect for one another as well as for their research in neuroscience. Dr. Gerard arrived at UC Irvine in 1964 and helped founding Chancellor Daniel G. Aldrich, Jr. organize the new campus. He was appointed the first Dean of the Graduate Division. Dr. McGaugh also arrived at UCI in 1964 and was interviewed by Dr. Gerard for the position of founding chair of Psychobiology, which is now known as the Department of Neurobiology and Behavior. Of Gerard, Dr. McGaugh remarks “I felt privileged to know him, as he had a highly distinguished career in physiology and was one of the founders of the Society for Neuroscience. After he retired he invited me to meet with him in his home on Friday afternoons for many interesting discussions of science, campus activities and other matters.” It is a fitting tribute to Gerard’s memory and the two scholars’ friendship that this lecture bear their names together. We extend our sincere gratitude to Dr. McGaugh and the Gerard family trust for their philanthropy in establishing this important lectureship at the CNLM to enrich the lives of future generations.

Basic Science Saves Lives – an idea worth remembering

The idea is not novel, but it is too often forgotten. Particularly in today’s political climate, the value of basic scientific pursuit and discovery is frequently challenged if not undermined. This is perhaps strange as science, by its very nature, is nonpartisan. It transcends political boundaries and reaches across all divides to unite us behind a common cause – to advance our collective state of knowledge, such that we may address humanity’s greatest challenges. Not long ago, Newt Gingrich wrote an op-ed in The New York Times calling for the National Institutes of Health funding for basic research to be doubled. He made the compelling case that it is a fiscally conservative policy, because more basic research would lead to better treatments, which would reduce federal healthcare spending. “When it comes to breakthroughs that could cure — not just treat — the most expensive diseases, government is unique. It alone can bring the necessary resources to bear,” Gingrich wrote. “And it is ultimately on the hook for the costs of illness. It’s irresponsible and shortsighted, not prudent, to let financing for basic research dwindle.”

Basic science, historically, has been at the root of transformational technological innovation. Perhaps the quintessential example is the biotechnology revolution that was borne out of the serendipity of basic research with recombinant DNA technology in the early 1970’s. A more recent example is the advent of “gene-editing” using the CRISPR/Cas9 system, a product of the fundamental question: how does a bacterium cope with a viral attack? This curiosity is what led to one of the most transformative applications in recent history – the very real possibility that genomic “errors” can be corrected, potentially preventing a number of diseases before they even begin. There are countless more examples of how basic science has been, and will always be the engine of discovery and innovation. It underlies all past and future breakthroughs in neuroscience and is the only means to fill the gaps in our understanding of the brain that prevent us from eradicating brain disease.

This is a message that I hope we can spread far and wide. I hope you will join the conversation and help support this cause by advocating for basic research and not losing sight of its critical importance for everything from curing brain disease to advancing human civilization.

 

Mike Yassa

 
– Adapted from the Spring 2017 CNLM Newsletter.

Click here to download the newsletter.