Spring 2023 Newsletter

MIND Matters

SPECIAL FEATURE

THE A4 STUDYA HEARTFELT THANK YOU

The topline results for the Anti-Amyloid treatment in Asymptomatic Alzheimer’s disease (A4) study were recently released (https://a4study.org) revealing the drug being investigated, solanezumab, failed to demonstrate a benefit in slowing memory changes in 65 to 85 year olds who met the criteria for preclinical Alzheimer’s disease (AD). Nevertheless, the A4 study was among the first ever preclinical AD trials, boldly blazing a trail that has now been followed by several other studies, including the open-to-enrollment AHEAD Study (www.aheadstudy.org).

Though the trial did not find that solanezumab will be an effective treatment for preclinical AD, the study has already taught the field an immeasurable amount. The trial leadership, including academic investigators and Eli Lilly, the maker of solanezumab, made the screening data for the trial publicly available shortly after recruitment had been completed.

Many important papers, including several by UCI MIND investigators have helped advance the field, increasing our understanding of the earliest biological and clinical changes in AD and improving the methods for conducting efficient and sensitive trials at the preclinical stage of disease. The full dataset for the A4 Study will also be made publicly available, giving investigators worldwide the opportunity to use this remarkable data to accelerate discovery.

“Although the results were not what we wanted or expected, we have learned so much from this study already and there is still so much more to learn with the data continuing to come in. This will help us build bigger and better trials like AHEAD and studies that come after it,” says Beatriz Vides, a clinical research nurse and the clinical trials manager for UCI MIND.

IN THIS ISSUE

The A4 Study

The Southern California Alzheimer’s Disease Centers Collaborative Conference

Inaugural Beall Scholar Award Recipient

Emerging Scientists Symposium

Alzheimer's Association Research Grant Recipient

New Staff

Retiring Staff

These advances and those that will come were made possible by the many participants and study partners who gave their time, energy, blood, sweat and tears to the A4 Study. Gaby Thai, MD, Principal Investigator of the A4 study at UCI MIND said, “I am very proud that I was part of A4. I am grateful we have such a dedicated team to help carry this study. I am also grateful to the participants and their families who devoted so much time and effort to help.” Many of the UCI MIND participants had been in the study since 2014, receiving infusions, undergoing cognitive testing, getting PET scans and providing fluid specimens. Furthermore, every participant was asked to enroll with a study partner who could also participate in study visits and assessments.

continued on page 3

Nurse practitioner, Melanie Tallakson (center) and clinical research nurse, Beatriz Vides, infuse a participant for the A4 study

MESSAGE FROM THE DIRECTOR

Dear friends of UCI MIND,

This spring newsletter includes a variety of ways in which the Alzheimer’s research torch is being passed at an exciting and important time in our history as a field. New drugs have been granted approval by the FDA and additional approvals may be on the way (page 1 and 3). This now includes two drugs approved under the FDA’s accelerated approval pathway, one of which may soon receive full approval, and one new drug for agitation. These advances were only possible because of the incredible research heroes who enrolled in and completed clinical trials of these medications. We honor the heroes who participate in studies for their contributions to our mission (page 1).

With a waning pandemic, researchers are coming together again (page 4) to discuss how to build on these successes and continue to accelerate our pursuit of even more meaningful treatment options for patients and families.

This spring and summer, UCI MIND is saying goodbye to a few key members of our team and welcoming others (page 7). While research remains our primary mission, training the next generation of clinicians and scientists has long been an area of emphasis and excellence at UCI MIND. Our outstanding trainees and early career researchers at UCI MIND make clear that the future is in very good hands indeed (pages 4 and 6).

FACULTY MEMBERS

Anatomy & Neurobiology

Aileen Anderson, PhD

Tallie Baram, MD, PhD

Christine Gall, PhD, Chair

Alan Goldin, MD, PhD

Kei Igarashi, PhD

Gary Lynch, PhD

Steven Schreiber, MD

John Weiss, MD, PhD

Xiangmin Xu, PhD

Biological Chemistry

Wei Li, PhD

Biomedical Engineering

Gregory Brewer, PhD

Chemistry

James Nowick, PhD

Xiaoyu Shi, PhD

Developmental & Cell Biology

Edwin Monuki, MD, PhD

Ali Mortazavi, PhD

Diane O’Dowd, PhD

Xiaoyu Shi, PhD

Environmental and Occupational Health

Masashi Kitazawa, PhD

Karen Lincoln, PhD, MSW, MA, FGSA

Epidemiology

Maria Corrada, ScD

Karen Edwards, PhD, Chair

Daniel Gillen, PhD

Sunmin Lee, ScD

Medicine

Masashi Kitazawa, PhD

Steven Tam, MD

Microbiology & Molecular Genetics

Emiliana Borrelli, PhD

Alan Goldin, MD, PhD

Molecular Biology & Biochemistry

Charles Glabe, PhD

Andrea Tenner, PhD

Neurobiology & Behavior

Mathew Blurton-Jones, PhD

Jorge Busciglio, PhD

Carl Cotman, PhD

Christine Gall, PhD

Kim Green, PhD

Joshua Grill, PhD

Claudia Kawas, MD

Frank LaFerla, PhD, Dean

Michael Leon, PhD

Craig Stark, PhD

Vivek Swarup, PhD

Leslie Thompson, PhD

Marcelo Wood, PhD, Chair

Michael Yassa, PhD

Neurology

Tallie Baram, MD, PhD

Maria Corrada, ScD

Carl Cotman, PhD

David Cribbs, PhD

Mark Fisher, MD

Lisa Flanagan, PhD

Claire Henchcliffe, MD, DPhil, Chair

Brian Hitt, MD, PhD

Claudia Kawas, MD

Albert La Spada, MD, PhD

Ira Lott, MD

Mark Mapstone, PhD

Tahseen Mozaffar, MD

S. Ahmad Sajjadi, MD, PhD

Steven Schreiber, MD

Gaby Thai, MD

John Weiss, MD, PhD

Michael Yassa, PhD

Pathology & Laboratory Medicine

Elizabeth Head, PhD, Vice Chair

Ronald Kim, MD

Albert La Spada, MD, PhD

Edwin Monuki, MD, PhD, Chair

Mari Perez-Rosendahl, MD

William Yong, MD

Joshua D. Grill, PhD Director, UCI MIND

Pediatrics

Tallie Baram, MD, PhD

Virginia Kimonis, MD

Ira Lott, MD

Andre Obenaus, PhD

Pharmaceutical Sciences

Emiliana Borrelli, PhD

Physical Medicine & Rehabilitation

Aileen Anderson, PhD

Brian Cummings, PhD

Physiology & Biophysics

Kevin Beier, PhD

Alan Goldin, MD, PhD

Psychiatry & Human Behavior

Joshua Grill, PhD

Gary Lynch, PhD

Bryce Mander, PhD

Joan Steffan, PhD

David Sultzer, MD

Leslie Thompson, PhD

Michael Yassa, PhD

Psychological Science

Daniel Nation, PhD

Radiation Oncology

Charles Limoli, PhD

Statistics

Daniel Gillen, PhD, Chair

Bin Nan, PhD

EVENT SPOTLIGHT

ANNUAL SOUTHERN CALIFORNIA COLLABORATIVE CONFERENCE

On May 10th, 2023, UCI, along with USC, Cedars Sinai, UCLA, and UCSD met for their annual Southern California Alzheimer’s Disease Centers Collaborative Conference. Faculty, trainees, and research staff from around the region gathered to share their work and learn about the latest advances in AD clinical practice and research. Two speakers from each organization, including one basic scientist and one clinical researcher, presented to a packed auditorium of engaged minds. Topics ranged from retinal biomarkers of AD and using machine learning to understand disease progression, to clinical trial design in an era of approved drugs and patient quality of life. UCI MIND faculty Vivek Swarup, PhD,

Assistant Professor of Neurobiology and Behavior, discussed AD genomics in humans and mice, and Karen Lincoln, PhD, MSW, MA, FGSA, Professor of Environmental and Occupational Health presented on brain health education and research in African American communities. One of the highlights of the event was a poster session held in the atrium of the Beckman Center, ending with awards to the best poster presenters (including to UCI MD/PhD trainee Yueqi Ren). The presentation of the posters and the subsequent reception and dinner facilitated collaborative conversations between the researchers, speakers, and audience.

Continued from Page 1: The A4 Study – A Heartfelt Thank

“Some people have been in the A4 Study for an amazing 10 years and all of them demonstrated a commitment to the AD research mission that is second to none. Words are not adequate to convey our gratitude to these participants and study partners who made A4 possible at UCI MIND and beyond,” said Joshua Grill, PhD, Director of UCI MIND and an A4 study investigator. “You are true research heroes, and we are indebted to you. Solanezumab may not be the answer we seek, but we will get there with the help of champions like you.”

Positive news on the horizon

Despite the somber news of solanezumab, Eli Lilly recently announced more promising topline results

You

for their monoclonal antibody donanemab, which was tested in a Phase 3 clinical trial to slow cognitive and functional decline in people with MCI and mild dementia. Based on their press release, donanemab was effective at removing amyloid plaques and slowing cognitive and functional decline in people with cognitive impairment. Lilly plans to present the full data at this summer’s Alzheimer’s Association International Conference and to seek FDA approval later this year. And for the first time, the FDA has approved a treatment for the challenging behavioral symptoms that are common in AD. Brexpiprazole was approved for the treatment of agitation in AD and hopefully will bring in a period of new advances for the development of symptomatic treatments.

Poster displays in the atrium Conference attendees listening to scientific presentations

Dr. Karen Lincoln delivers a presentation

Poster winners: Yueqi Ren (left) and Amanda Tse, USC

RESEARCH UPDATE

INAUGURAL BEALL SCHOLAR AWARD RECIPIENT IS NAMED

Seyed Ahmad

Sajjadi, MD,

PhD, an Associate Professor of Neurology and Associate Professor of Pathology, was named the inaugural recipient of the UCI MIND Joan and Don Beall Scholar Award. The award, announced earlier this this year and named after the steadfast UCI MIND supporters, will provide $50,000 per year for 5 years with a one-time opportunity to renew funding. The money will help facilitate research projects in Dr. Sajjadi’s lab, which is focused on understanding the pathophysiological underpinnings of Alzheimer’s disease and related dementias. “The award will enable us to pursue projects to identify serological biomarkers for a common but less recognized form of degenerative

UPCOMING EVENT

Join

Over the past decade, UCI MIND has raised in excess of $2 million at the annual dinner with all funds going directly to Alzheimer’s research.

gala.mind.uci.edu

brain pathology called Limbic predominant age related TDP-43 encephalopathy (LATE). Moreover, it will help generate the preliminary data required for applications that we submit to NIH and other large funding bodies, “ says Dr. Sajjadi.

Dr. Sajjadi has been a faculty member of UCI since 2016. He received his medical degree from Tehran University and his PhD in neuroscience from the University of Cambridge. He serves at UCI in both clinical and research capacities. In addition to seeing patients in his memory disorders clinic, he is one of the research physicians at UCI MIND for the ADRC longitudinal cohort and the 90+ Study. He has also served as principal investigator for clinical trials in Alzheimer’s disease and mentors trainees. His NIHfunded research emphasizes distinguishing differing causes of cognitive impairment and dementia. “This award is a much-appreciated recognition of the efforts of our lab in developing biomarkers for less common forms of dementia that, at present, cannot be diagnosed during life.”

S. Ahmad Sajjadi, MD, PhD

AWARD

POSTDOCTORAL FELLOW AWARDED ALZHEIMER'S ASSOCIATION RESEARCH GRANT

Elizabeth Head, PhD, fellow lab members and other UCI colleagues.

Lisi Flores-Aguilar, PhD, a postdoctoral scholar in the Head Lab, was awarded a fellowship grant from the Alzheimer's Association on May 3rd for her innovative research on Alzheimer's disease and Down syndrome. A check presentation ceremony was held at UC Irvine, where she was honored by chair members from the Alzheimer's Association along with her advisor,

THANK YOU TO OUR DONORS

Gifts of $100,000+ (March ’22-’23)

Anonymous

Brethren Community Foundation

The Crean Foundation

Chris & Kathleen Taylor

Harris Taylor Family Foundation

Draper Family Foundation

Carla Liggett and Arthur S.

Liggett, M.D. Endowment

The Leandro P. Rizzuto Foundation

Western Geriatric Research Institute

The Women’s Alzheimer’s Movement

Gifts of $50,000+ (March ’22-’23)

Anonymous

Jacqueline DuPont-Carlson & Marc Carlson

Carole Harris

Harriet Harris

J. Stanley & Mary W. Johnson

Family Foundation

Joseph H. Stahlberg Foundation

Ueberroth Family Foundation

Gifts of $5,000+ (March ’22-’23)

Anonymous*

Lisa Applebee

Joseph & Lisa Banning

The Beall Family Foundation

Mary Behrens

Lorna Seema Carlin, M.D.

Jerry & Lucyann Carlton

Crevier Family Foundation

The John Curci Family Foundation

Richard & Billie Deihl

Barbara J. Dove

Eastern Produce Council, Inc.

Nancy Imlay Edwards Foundation

William Edwards

Eichenberg-Larson Charitable Foundation

James & Janet Gianulias

Richard & Mary Godber

Joseph Gonzalez

1996 David E. Griswold Marital

Trust

O.L. Halsell Foundation

Stephen & Janice Hamill

Bill & Sheila Harris

Carole Harris

Bill P. Harris & Sheila Finnegan

Harris

Dr. Flores-Aguilar completed her undergraduate degree in Mexico and her doctorate in anatomy and cell biology at McGill University, where she began to study Alzheimer's disease in people with Down syndrome. “It was at McGill when I first learned about the link between Alzheimer's disease and Down syndrome and I think it's super interesting. This is a population that has been understudied. I really want to contribute to know more about it, like how Alzheimer's develops in people with Down syndrome” said Dr. Flores Aguilar. When asked how this award will help her research, Dr. Flores-Aguilar said it's a “great opportunity for me to have funding and go to my next career step as an independent investigator.” The Alzheimer’s Association award will specifically support her research on blood-brain barrier pathology in Down syndrome and Alzheimer’s disease.

Hilarity for Charity

Julie & Peter Hill

John & Debra Hornsby

J. Stanley & Mary W. Johnson

Family Foundation

Frank & Susan Kavanaugh

Roger Lisabeth

Karen & Charles Loeb

Mohannad & Rana Malas

Masonry Fireplace Industries, Inc.

Don & Sharon McLaughlin

Suzanne Melin

Herbert & Loretta Modelevsky

Robert & Virginia Naeve

O’Connor Mortuary

Stephen & Ruth O'Leary

Orco Block & Hardscape, Inc.

Jeffrey & Diane Osborn

Alvin Pfeiffer

Charles Quilter, Ph.D. & Ann

Quilter

Patrick Quilter

Susan & John Reese

Fred & Wendy Salter

Richard & Lia Salus

Silverado Senior Living

Jo Skibby

Sperry Commercial & Sperry

Equities

Rand & Rosemary Sperry

Thomas & Marilyn Sutton

Keith Swayne

Tenebaum Family Fund

Chris & Kathleen Taylor

Warren & Jennifer Taylor

Kathryn Kendall & Dr. David

Thomsen

Andrew & Karen Thorburn

Ueberroth Family Foundation

Peggy Woelke Estate

Burton & Linda Young

F. Michael and Roberta

Simmons Wong Fdn

UCI MIND Legacy Society (Donors who have included UCI MIND in their estate plan)

Anonymous*

Shirley Bloom

Lorna Seema Carlin, M.D.

William Robert Chase, D.D.S.

Evelyn Freed

Bill Harris & Sheila Finnegan

Harris

Paula Hunter

Carol Murrel

Richard & Nancy Muth

In Memory of Patricia Ruth

O’Leary

Karen Rockel Speros

* Indicates multiple donors.

From left to right: Deborah Levy (Alzheimer's Association Orange County Chapter), Dr. Lisi Flores-Aguilar and Dr. Elizabeth Head

TRAINING AND EDUCATION

On Monday, April 17th, 2023, the trainee-led Research and Education in Memory Impairments and Neurological Disorders (REMIND) held its 14th Annual Emerging Scientists Symposium. The event is designed to help early career scientists share their research and network with colleagues and mentors. Like previous years, this symposium included research talks from invited trainees, poster presentations, and a keynote presentation. Microglial replacement, clinical trial design, mouse model genomics, and novel Alzheimer’s biomarkers were just a few of the topics covered by speakers and poster presenters. The REMIND co-chairs were honored this year to welcome Rema Raman, PhD, Professor of Neurology at the Keck School of Medicine at USC, to speak on “Advancing Alzheimer’s clinical trials through a convergence of statistics, machine learning and Al.” “The REMIND symposium is important to trainees as it provides graduate students and postdoctoral scholars the chance to present their work to their peers and faculty. It promotes collaboration within the UCI community and highlights the breadth of science that is being conducted at UCI and specifically in UCI MIND”, says Claire Butler, PhD, a postdoctoral scholar in Dr. Kim Green’s lab.

The REMIND Co-Chairs with Keynote Speaker, Rema Raman, PhD, USC, UCI Director, Joshua Grill and Associate

One of the highlights of the annual event is a poster competition. This year, Dr. Vaisakh Puthusseryppady a postdoctoral fellow in the Chrastil Lab was selected for his poster on spatial navigation in AD. Yueqi Ren, a MD/PhD candidate from the Stark Lab, won for her work on the development of diagnostic prediction models.

The afternoon concluded with a presentation of the Carl W. Cotman Scholar Awards, given to two trainees selected by a faculty committee for their standout achievements in brain aging research here at UCI. Xiaoxiao Lin, a graduate student in the Xu Lab, and Dr. Thai Nguyen, a postdoctoral scholar in the Thompson Lab, were recognized with a plaque and a $250 cash prize.

Carl W. Cotman Award winners, Thai Nguyen (left) and Xiaoxiao Lin, with Joshua Grill

Graduate trainee, Yiren Xu, discusses her research with Dr. Raman

Joshua Grill with poster award winners, Yueqi Ren and Vaisakh Puthusseryppady

WELCOME: DEBBIE MORALES AND SASHA STONE

Debbie is the digital communications specialist for UCI MIND. She has a bachelor’s degree in web design and interactive media from The Art Institute of California – Orange County. Debbie will manage the UCI MIND websites, handle email marketing, create graphic design, maintain all the social media platforms, etc. While learning more about UCI MIND, her goal is to grow the Institute’s presence in our community and share the amazing work we are doing in Alzheimer’s research!

Sasha has joined the UCI MIND team as an event specialist. She will be assisting with the planning and coordination of both small- and large-scale events. In her previous work as a program coordinator at UCI, she managed three grant-based programs, as well as designed and created digital material for educators. She looks forward to organizing events that are engaging and informative and is excited to learn more about the important research being done at UCI MIND.

HAPPY RETIREMENT: LUTER, LINDA AND OLIVIA

MIND. Olivia served as an administrative assistant for UCI MIND for 5 years under Carl Cotman, PhD, and then more broadly for the Institute. All three women will be retiring at the end of June and will be greatly missed by our team and our community at large. We thank them for their exemplary service over the years.

UPCOMING EVENT

This spring, we will say goodbye to three critical members of the UCI MIND family who have made significant contributions to our mission. Luter Liu, our Chief Financial Officer, has been with UCI MIND since 1995 and with the University for 36 years. Linda Scheck, Director of Development, was brought on by Frank LaFerla, PhD in 2008 to raise awareness and then lead philanthropy in 2012. Prior to her tenure at UCI MIND, Linda was the Executive Director at the Alzheimer’s Association, Orange County Chapter. Olivia Perez’s career started in UC Irvine's Department of Neurology in 2003. In 2016, she began working with Dr. Claudia Kawas, and a year later she joined UCI

From left to right: Olivia Perez, Linda Scheck and Luter Liu

August 25, 2023

conference.mind.uci.edu

Institute for Memory Impairments and Neurological Disorders

2643 Biological Sciences III Irvine, CA 92697-4545

The UCI MIND Alzheimer’s Disease Research Center is supported by the National Institute on Aging (NIA) of the National Institutes of Health (NIH) under award number P30 AG066519.

This newsletter is supported in part by the California Department of Public Health, Alzheimer’s Disease Program. Funding is pursuant to California Health and Safety Code Section 125275 – 125285.

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