Introduction to the Annual Report - Arizona Alzheimer's Consortium

339 Pages·2014·3.31 MB·English

by  Winnie Liang

ANNUAL REPORT

July 1, 2013 to June 30, 2014
Table of Contents

Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Page 5

Annual Scientific Conference Agenda. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Page 9

Institutional Information. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Page 35

- Research Summaries

- Key Personnel

Project Progress Reports . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Page 66

- Project Progress Reports by Institution

2013-2014 Publications, Manuscripts, & Grants

- Publications and Manuscripts. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Page 170

- Current and Pending Grants. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Page 195

Poster Abstracts. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Page 223

Institutional Budgets and Justifications . . . . . . . . . . . . . . . . . . . . . . . . . . . . See companion report

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In memory of our dear colleague D. Larry Sparks, PhD,
who passed away on May 12, 2013.

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Introduction to the Annual Report

Background

The Arizona Alzheimer’s Consortium is the nation’s leading model of statewide collaboration in
Alzheimer’s disease (AD) research. It includes about 150 researchers and support staff from seven
principal organizations--Arizona State University, Banner Alzheimer’s Institute, Banner Sun Health
Research Institute, Barrow Neurological Institute, Mayo Clinic Arizona, Translational Genomics Research
Institute (TGen), and University of Arizona--and from several affiliated organizations, including
Midwestern University, the Critical Path Institute, and the University of Arizona College of Medicine,
Phoenix Campus. Established in 1998, the Consortium is intended to make a major difference in the
scientific fight against AD, and to help address the unmet needs of patients and family caregivers.

The Consortium continues to be recognized inside and outside Arizona as a model of multi-
institutional collaboration in biomedical research, capitalizing on complementary resources and expertise
from different disciplines and institutions to address scientific problems in a more fundamental way. Its
researchers receive critical support from the state of Arizona (through the Arizona Department of Health
Services [ADHS] and its Arizona Biomedical Research Commission [ABRC]), the participating
institutions, a competitive Arizona AD Center (ADCC) grant from the National Institute on Aging (NIA),
and many other grants and contracts.

Dr. Eric Reiman is the Director of the Consortium and the NIA-sponsored ADCC, Dr. Richard Caselli
is the ADCC’s Associate Director, and Dr. Carol Barnes is Chairperson of the Consortium’s 25-member
Internal Scientific Advisory Committee. Leading officials from each of the seven principal institutions
serve on the Consortium’s Board of Directors. The Consortium’s external advisors include Drs. Marilyn
Albert, Zaven Khachaturian, and Bruce Miller, who are recognized for their pioneering contributions and
leadership roles in the study of AD and related disorders. They conduct an annual site visit, review the
progress and productivity of the Consortium and the ADCC, and provide formal feedback and
recommendations to the researchers, NIA and state.

The Arizona Alzheimer’s Consortium capitalizes on the state’s strengths in brain imaging, genomics,
the computational and mathematical analysis of complex data sets, the basic, cognitive and behavioral
neurosciences, and clinical, experimental therapeutics, and neuropathology research. It has made critical
contributions to the scientific understanding, unusually early detection and tracking of AD, and
accelerated evaluation of putative AD prevention therapies. It has provided a national model of multi-
institutional research collaboration, and has found new ways for different stakeholders to work together in
support of critically important goals.

The Consortium’s major themes are the early detection and prevention of AD. Its primary goal is to
find effective treatments to stop and end AD as quickly as possible. It has also sought to make a difference
in the lives of all patients and families affected by or at risk for AD, including Arizona’s underserved and
understudied Hispanic and Native American communities.

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State and institutional matching funds are used to provide the “glue” for this geographically distributed
research program, the “fuel” needed to launch new research initiatives, and the framework needed to reach
the Consortium’s over-arching goals. Funds are used to support dozens of research projects each year,
almost all of which involve researchers from different scientific disciplines, and about half of which
include researchers from different institutions.

The Arizona ADCC has received competitive NIA grant support for 13 consecutive years. Funds for
ADCC’s Administrative, Clinical, Data Management and Statistics, Neuropathology, and Education and
Information Transfer Cores are used to support a larger number of researchers and projects inside and
outside of the state. ADCC’s progress, productivity and plans were detailed in our annual report to the
NIA, will be reviewed at our advisors’ annual site visit on June 6, 2014 and will support the submission of
our fourth consecutive competitive five-year ADCC renewal grant in September 2015.

Productivity and Impact

The Arizona Alzheimer’s Consortium is the leading statewide AD Center in the nation and among the
most impactful AD research programs in the world. To date, its researchers have generated several
thousand publications, close to a thousand research grants and contracts, hundreds of millions of dollars in
grants, contracts, philanthropy, new research programs and facilities, and numerous jobs. They continue to
make pioneering contributions to the scientific fight against AD, related disorders, and the aging brain.

They have helped clarify several genetic and non-genetic risk factors and disease mechanisms,

providing targets at which to aim new AD treatments, and they have proposed promising ways to treat
and prevent the disorder.

They continue to play leadership roles in the earliest detection and tracking of AD and the accelerated

evaluation of putative prevention therapies. They have also helped set the stage for the use of amyloid
imaging techniques in the clinical setting.

They continue to clarify how brain cells, regions, and networks, and the mental operations to which they

are related, work together to orchestrate memory and other thinking abilities, how they are preferentially
affected by AD and by normal aging. They have played leadership roles in the study of normal cognitive
aging.

They continue to develop groundbreaking research methods and strategies to support these and other

research endeavors.

As previously noted, they established an “Alzheimer’s Prevention Initiative (API)” to help launch a new

era in AD prevention research. API’s first trial, which is supported by more than $100M in funding from
the NIA, philanthropic funds, and Genentech, began in late 2013. It is intended to evaluate an amyloid
antibody therapy in cognitively unimpaired persons at certain risk for autosomal dominant early-onset
AD, provide a better understanding of the “amyloid hypothesis,” help to establish the biomarker
endpoints and accelerated approval pathway needed to rapidly evaluate the range of promising
prevention therapies; and provide a public resource of therapeutic trial data and biological samples to the
research community after the trial is over. API’s second trial, which will be the supported by a recent
$33.2M NIA grant award, additional funds from the NIA’s Accelerating Medicine’s Partnership,
philanthropy, and a to-be-determined industry partner will evaluate one or more anti-amyloid agents in
cognitively unimpaired persons with two copies of the APOE4 gene, who are at the highest known risk
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for developing AD at older ages. Alzheimer’s Prevention Registries have been launched in Colombia
and in North America (www.endalznow.org) to support enrollment in prevention trials.

We are pleased to note that Dr. Carol Barnes was the recipient of the 2013 Ralph W. Gerard Prize in

Neuroscience from the Society for Neuroscience in recognition of her seminal contributions to the study
of the aging brain. The Gerard Prize is the top recognition given by the Society for Neuroscience and it
has been reserved for giants in brain research.

More to Do

While we are gratified by the Consortium’s productivity, we recognize that there is a lot more to do.
During the next few years, we wish to increase the critical mass of productive clinical and basic scientists
in Arizona, to launch several new scientific and clinical initiatives, to set a new standard for the care of
patients and families, to further assist our understudied and underserved communities, and to help find
treatments to prevent the clinical onset of AD as soon as possible.

We wish to express our heartfelt appreciation to the state of Arizona, the NIA, our participating
institutions, and all of our partners, supporters and valued research participants. We are especially grateful
to our elected officials, the ADHS, and the ABRC for increasing our state funding from $1.15M to
$2.375M during the next fiscal year. We are proud of our progress, excited about our plans, and
determined to make a transformational difference in the fight against AD.

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Arizona Alzheimer’s Consortium
16th Annual Conference – Thursday June 5, 2014
Banner Desert Medical Center
1400 S. Dobson Road
Mesa, Arizona 85202

POSTER PRESENTATION SET-UP 7:30 – 9:00AM
CONTINENTAL BREAKFAST

WELCOMING REMARKS & INTRODUCTION 9:00 – 9:15AM
Eric M. Reiman, M.D.
Director, Arizona Alzheimer's Consortium

LEON THAL MEMORIAL LECTURE 9:15 – 10:30AM
"Building a Pipeline to Identify and Validate Novel
Targets for the Treatment and Prevention of Alzheimer’s
Disease"
David A. Bennett, M.D.
Director, Rush Alzheimer’s Center
Robert C. Borwell Professor of Neurological Sciences
Rush University Medical Center

ORAL RESEARCH PRESENTATIONS – SESSION I 10:30 – 12:00PM

POSTER SESSION I & LUNCH 12:00 – 1:00PM

POSTER SESSION II & LUNCH 1:00 – 2:00PM

ORAL RESEARCH PRESENTATIONS – SESSION II 2:00 – 3:10PM

CLOSING REMARKS 3:10 – 3:30PM
Eric M. Reiman, M.D.
Director, Arizona Alzheimer's Consortium

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Arizona Alzheimer’s Consortium

Oral Research Presentations

SESSION I (Moderator: Dr. Richard Caselli, M.D.)

10:30 - 10:42AM mTOR regulates tau phosphorylation and degradation: implications for
Alzheimer’s disease and other tauopathies. Salvatore Oddo. Banner Sun Health
Research Institute; University of Arizona College of Medicine, Phoenix; Arizona
Alzheimer’s Consortium.

10:43 - 10:55AM PACAP deficit in Alzheimer’s disease and protection against beta-amyloid
toxicity. PengCheng Han. Barrow Neurological Institute; The First Hospital of
Kunming Medical University; Banner Sun Health Research Institute; Banner
Alzheimer’s Institute; Arizona Alzheimer’s Consortium.

10:56 - 11:08AM Protein aggregates as biomarkers for neurodegenerative diseases. Michael Sierks.
Arizona State University; Arizona Alzheimer’s Consortium.

11:09 - 11:21AM Novel method for behavior-driven molecular and structural investigation in
rodent whole brain. Monica Chawla. University of Arizona; Alzheimer’s
Consortium.

11:22 - 11:34AM Relationships between behavioral declines, hyperexcitability, and inhibitory
networks in the medial temporal lobe of aged rhesus macaque. Daniel Gray.
University of Arizona; Arizona Alzheimer’s Consortium.

11:35 - 11:47AM Improving the power to track fibrillar amyloid-beta PET measurements and
evaluate amyloid-modifying treatments using a cerebral white matter region-of-
interest. Kewei Chen. Banner Alzheimer’s Institute; Arizona Alzheimer’s
Consortium.

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