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Winter 2016 E-Newsletter

Winter 2016 UCLA Alzheimer's Research Center Newsletter

| Welcoming New Interim Director | UCLA Memory Disorders Clinic |
| Dietary Factors & Lifestyle to Prevent AD | Longitudinal Aging Study |
| UCLA MSTAR Program | We Have Moved | Clinical Trials | Upcoming Events |

Welcome Our New Center Interim Director

Welcome New Center Interim DirectorPhoto: Gregory M. Cole, Ph.D.

Greg M. Cole, Ph.D., Professor of Neurology and Medicine and our new Interim Director received undergraduate degrees in Physics and Biochemistry from UC Berkeley where he also obtained his PhD conducting some of the first studies on oxidative damage, beta amyloid (Aß) and the molecular tagging of abnormal proteins like tau in Alzheimer Disease (AD). He moved to the UCSD’s Alzheimer Center carrying out early studies on the source protein for Aß (amyloid precursor protein) and the molecular biology of AD, and quickly advanced to a faculty position. While at UCSD, he and colleague Dr. Sally Frautschy carried out seminal studies on in vivo amyloid toxicity and its removal by innate immune cells before both were recruited to UCLA in 1993. Once at UCLA, they worked with Dr. Cummings, the founding Easton Center Director, Dr. Harry Vinters, and other UCLA colleagues to establish an AD Research Center at UCLA.

Dr. Cole joined a UCLA team also including Drs. Small and Barrio to develop and patent the first amyloid PET imaging probe. To monitor the development of AD, his group developed antibodies to probe cell death pathway activation and to detect pathogenic abeta 42. They collaborated with Dr. Karen Hsiao Ashe at the University of Minnesota to develop the first successful academic transgenic mouse model for AD and enlisted this and other preclinical AD models in the search for drugs to treat or prevent AD. He and Dr. Frautchy pioneered four interventions that quickly went into clinical trials. For these pioneering studies, Dr. Cole and his group received continuous NIH support, a Zenith Award from the Alzheimer Association and, in 2009, were one of the very few investigators to receive a "Challenge Grants", joining the 1% of scientists to receive this award among 20,000 competitors across all medical fields. More recently, they were fortunate enough to receive additional Easton support that has enabled studies on CSF and blood biomarkers in patients, new AD preclinical models including transgenic rats demonstrating all aspects of the AD pathology and transgenic mice with variants of the human ApoE gene, the major determinant of genetic AD risk. Ongoing studies in these models and patient blood samples have allowed the discovery of new blood biomarkers for sick synapses (with Dr. Edmond Teng) and two new mechanisms that help explain how ApoE variants act to increase AD risk and what we can do about it.

Dr. Cole's primary goal has been to develop safe and widely available methods for the prevention and possible treatment of Alzheimer's and other neurodegenerative diseases of aging. Discovering treatment and preventions methods is necessarily collaborative and wherever possible, the Cole and Frautschy team collaborate on new therapeutics with other Easton Center members and affiliates among the UCLA faculty (Drs. Bitan, Teplow, Eisenberg, John, and Bredesen). While potential drug candidates have emerged, Dr. Cole argues that it takes far too much money ($50 to 100 million) and time (5-7 years) per trial to determine whether or not the drug works. Dr. Cole believes that the missing tool we need is the development of safe, quick and inexpensive tests for “biomarkers” that can serve as measures of drug efficacy. For example, to prevent heart disease, we use statin drugs (Lipitor, etc.) to lower blood levels of bad cholesterol and triglycerides, which are now, an established “surrogate biomarker” for heart disease risk. There are no similar blood tests yet for AD and we need to develop one. Dr. Cole has joined in the hunt for blood measures that can provide feedback on AD management with other Easton Center investigators and UC faculty. They are seeking funding to continue to explore the biomarker information in very small membrane bound bags (exosomes) released into the blood by brain cells that appear to report on the current status of disease activity in real time. Dr. Cole's lab is also developing new targets and biomarkers reflecting defects caused by the major genetic risk factor for AD, the ApoE4 variant of Apoliopoprotein E. He is confident that successful blood tests will reduce the cost and time for initial clinical trials as much as 10-fold and help us rapidly find the best doses and formulations for new drugs. As our new Interim Director, Dr. Cole’s goal will be to help us develop and fund great collaborative teams that can draw on UCLA’s depth of expertise, and foster breakthroughs that make a real difference in clinical care and prevention.

Please join us in welcoming Dr. Greg Cole as the Easton Center new Interim Director!

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UCLA Memory Disorders Clinic Open House

UCLA Memory Disorders ClinicPhoto: (left to right) Barbara Dwyer; Ellen Woo, PhD; Verna Porter, MD; Sarah Kremen, MD; Kathleen Tingus, PhD; Christopher Nunez, PhD; Nancy Osuch.

On November 12, 2015 the newly designed UCLA Alzheimer’s Dementia and Memory Disorders Clinic opened its doors for a community open house reception at UCLA 100 Medical Plaza, Suite 425. The evening provided the opportunity for interactions among our academic, community and patient liaison groups in the broader Los Angeles community. It also provided a chance for tours of this newly configured space and an opportunity to learn more about our multidisciplinary approach to patient care.

UCLA Memory Disorders Clinic“ width=“205px
This space houses the physician clinical evaluation rooms, neuropsychology services and also allows patients contact with other rotating subspecialists in neurobehavior, neurogerontology, gait/balance disorders and general neurology. Our leadership team was also introduced, including the Interim Chair of the Department of Neurology, Dr. Marie-Francoise Chesselet, the Director of Clinical Programs, Dr. Verna Porter, the Director of Neuropsychology, Dr. Ellen Woo and the Director of the Neuropsychology Clinic, Dr. Kathleen Tingus. Leaders from our Clinical Trials Program, including Dr. Sarah Kremen were also present to answer questions.

The goals of this new clinic include high patient accessibility to consultations and the latest technologies for assessing memory and cognitive decline, including such services as full neuropsychological assessments, volumetric MRI imaging modalities and the latest functional imaging techniques such as FDG and amyloid PET scanning. In addition, there is an ongoing partnering of all our clinical services with other services within the UCLA Mary S. Easton Center, including clinical trials, community outreach and educational services, and partnering with our colleagues in Geriatrics through the UCLA Alzheimer’s and Dementia Care Program. The UCLA Alzheimer’ and Dementia Care Program is a nurse practitioner run program to help connect patients and families with university and community resources while assisting with coordination of clinical care. We are looking forward to the continuing development of the Dementia and Memory Disorders Clinic under the leadership of the new Interim Director of the Mary S. Easton Center, Dr. Gregory Cole.

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Dietary Factors and Lifestyle to Prevent Alzheimer's Disease

Sally Frautschy, PhDPhoto: Sally Frautschy, Ph.D.

Dr. Sally Frautschy is a Professor in the Department of Neurology with secondary appointment in the Department of Medicine, David Geffen School of Medicine at UCLA and Chief of Neurogerontology in the Geriatric Research Education Clinical Center (GRECC) at the Veterans Administration. Dr. Frautschy has published over 90 papers, primarily on AD and serves on the editorial boards for the Journal of Neuroinflamation and Journal of Biological Chemistry and many scientific review panels for the NIH, Alzheimer's Association, and VA. She completed degrees (B.A. Spanish Lit, B.S. Biology) at UC Davis and received the College of Biological Sciences award for top student, staying at Davis for her M.S. before obtaining a Biomedical Science Ph.D. (Guelph, Canada) studying adverse neuroendocrine impacts of chronic stress. After completing neuroendocrine studies as a post-doctoral Fellow at the Salk Institute and UCSD, she developed an NIH funded research faculty program at the Scripps Institute (La Jolla) on the effect of brain-derived trophic factors on AD. In 1990, she began injecting amyloid cores isolated from AD brains into the rat brain and developed the first in vivo model to determine the effects of natural beta-amyloid toxicity and clearance in the brain. She demonstrated that amyloid induced tau pathology, oxidative damage and inflammatory changes before being cleared into the vessels via innate immune cells (macrophages). This clearance by innate immune cells is a therapeutic mechanism that was later (1999) found to be stimulated by amyloid vaccines developed by pharmaceutical industry researchers.

After receiving two NIH grants, she was recruited to UCLA and its VA affiliate in 1994 to work with Dr. Jeffrey Cummings, the Alzheimer’s Program director, to help obtain NIH funding for a UCLA Alzheimer’s Disease Research Center (ADRC). In 1996, along with Dr. Cole, she embarked on the first translational studies in the field using her newly developed abeta infusion models as well as one of the first transgenic models developed in collaboration with Dr. Karen Hsiao Ashe at University of Minnesota. Since epidemiology suggested that people who took anti-inflammatory medications (like ibuprofen) had lower risk for AD, Drs. Frautschy and Cole, tested their activity in these new animal models and found beneficial effects of anti-inflammatory agents (ibuprofen, R-flurbiprofen, curcumin and DHA, an Omega-3 fatty acid) which all advanced to clinical trials. Since the typical mouse chow is rich enough in fish meal and omega 3 fatty acids to be similar to a potentially protective "Japanese" diet, they sought to evaluate whether standard mouse chow or added DHA or fish oil protected AD model mice from Alzheimer degenerative changes such as brain volume loss. They discovered that Omega-3 exerted multiple protective effects: reducing loss of nerve cell connections, amyloid formation, brain insulin resistance, and dysregulation of pathways involved in cognitive deficits. Because fish oil enriched in DHA is safe and inexpensive, testing has gone forward and recently shown significant benefits in European “multidomain” clinical trials combining omega 3 with exercise, cognitive therapy and vitamins. Similar trials are being planned in the US.

Dietary Factors and Lifestyle to Prevent Alzheimer's Disease - Sally Frautschy
Using the animal models for testing compounds that protect against oxidative damage and aberrant inflammation, she identified a compound, curcumin, a pigment from the turmeric root (a relative of ginger) that targets many pathways involved in AD, reduces inflammation and oxidative damage, prompts the immune system to remove amyloid from the brain, and directly blocks toxic Abeta and tau aggregates (oligomers). After a UCLA trial with commercially available curcumin failed to produce adequate blood levels or patient benefits, she obtained NIH funding to improve curcumin bioavailablity, which led to a new formulation that just received a UCLA patent. This new curcumin formulation is now in multiple clinical trials at many sites, including a trial at our VA affiliate in Brentwood in patients with mild cognitive impairment directed by Easton Center faculty, Drs. Frautschy and Teng.

Dr. Frautschy’s current basic research program is focusing on understanding how disruption of normal brain inflammation affects the mechanisms immediately preceding nerve cell loss. With new support from the Paul Allen Foundation and the Department of Defense (DOD), she focuses on a particularly damaging form of inflammation that punctures nerve cell membranes. However, much of Dr. Frautschy’s activity has shifted to clinical research. With her collaborators, she is seeking funding to continue human clinical trials examining curcumin and exercise intervention (yoga) to prevent Alzheimer's disease in individuals with mild cognitive impairment.

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Longitudinal Aging Study

“LongitudinalPhoto: Ellen Woo, Ph.D.

Dr. Ellen Woo, Director of Neuropsychology for the Easton Center and the Alzheimer Disease Program in the Department of Neurology, is the principal investigator of the Longitudinal Aging Study. The focus of this study is to detect older adults’ cognitive difficulties that are more relevant in a real world setting than in the laboratory. Specifically, the overarching goal of the study is to determine which cognitive difficulties will predict who will exhibit declines in activities of daily living (ADLs), which are the everyday skills that help individuals maintain their independence.

Persons with even mild cognitive impairment can exhibit subtle deficits in instrumental ADLs (IADLS), which are higher-order activities such as financial and medication management. IADLs are greatly impacted by cognitive changes, such as in memory; cognitive difficulties can have serious consequences for everyday functioning, such as missed medical appointments. For patients, cognitive impairment can also lead to poor self-confidence, anxiety, depression, and withdrawal from everyday activities. Therefore, cognitive problems affect multiple aspects of a person’s real-world functioning.

This research will examine the multiple factors that are associated with cognitive and everyday functions in older adults. In addition, caregivers report that the cognitive changes of their loved ones also impact their own functioning, which is important to examine.

You may be eligible to participate in the Longitudinal Aging Study if you:

  • Are fluent in English.
  • Age 50 or older.
  • Are healthy controls, have a preliminary diagnosis of Mild Cognitive Impairment or dementia, or have concerns about cognition.
  • Have a study partner (someone who has weekly contact with you, is willing to accompany you to the initial study visit, and can answer questions about how you are doing on a yearly basis).

Potential study participants will receive an evaluation from a study physician and also undergo neuropsychological testing for an assessment of current cognitive functions. As such, they will receive a research summary indicating how they performed on the standard cognitive measures compared to their age and/or education peers and compared to their performances on the previous year of participation. The study partners will complete questionnaires regarding the participants’ functioning. Participants and study partners will continue in the study on a yearly basis.

We are very excited to be conducting this important study. If you think you might be interested in volunteering for this study, please contact us at (310) 794-2804.

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UCLA MSTAR Program

UCLA MSTAR Program - Edmond Teng, MD, PhDBy: Edmond Teng, M.D., Ph.D.

The proportion of older adults (age 65 and above) in the population of the United States and other industrialized countries is rapidly increasing. However, the numbers of physicians and other health care professionals specializing in the care for older patients lag far behind the projected needs. These factors indicate that current medical school curricula may not be training enough clinicians to meet the growing medical demands associated with aging. Fortunately, some studies suggest that medical students who participate in aging research are more likely to pursue careers in aging research, medical education or clinical care.

The UCLA Medical Student Training in Aging Research (MSTAR) program exposes medical students to aging research and the clinical care of older patients during the summer between their 1st and 2nd years. It encompasses formal didactic lectures, clinical shadowing, and an intensive research project supervised by a faculty mentor with whom the student is matched. UCLA has been an MSTAR program site for 20 years but in recent years we have also incorporated distal sites at the University of Washington, University of Colorado, and UCSF. Since its inception, our MSTAR program has trained over 400 students from institutions across the country. The MSTAR program is partially supported by a training grant from the National Institute for Aging and also receives limited administrative support from the American Federation for Aging Research.

MSTAR is based in the Division of Geriatrics, but the Department of Neurology has been closely involved in this program for a number of years. I am currently one of the Co-Directors of MSTAR (along with Drs. Alison Moore and Jonathan Wanagat). Given the association between aging and a wide spectrum of neurological conditions, particularly neurodegenerative diseases such as Alzheimer’s disease, there are clear synergies between the MSTAR program, the Easton Center for Alzheimer’s Disease Research, and the Department of Neurology. The primary goal of the MSTAR program is to increase the numbers of clinician-researchers that pursue careers in aging across a broad range of clinical specialties, including neurology and dementia care.

MSTAR students rotate through our Neurobehavior Clinic at the West Los Angeles VA, and since 2010, approximately 30% of them have worked with faculty mentors from the Department of Neurology, including Drs. Thomas Carmichael, Harry Vinters, Mario Mendez, Lucas Restrepo, and myself. MSTAR research has ranged from basic science (“Mechanisms of neuronal regeneration after stroke”) to clinical (“Neuropathic substrates of dementia,” “Biological underpinnings of cognitive expression of brain aging”) to health services (“Measuring quality of care for vulnerable elders”). Many of these summer projects eventually result in abstracts presented at national meetings, research awards, and/or peer-reviewed publications. One of our goals is to increase the number of students from underrepresented groups who in the UCLA MSTAR program in coming years, as there is a great need to increase the diversity of the pool of physicians who pursue a career in aging research and clinical care.

If you would like more information regarding the UCLA MSTAR program, or would like to support the program as a research mentor or through philanthropy, please visit the MSTAR website (http://www.geronet.ucla.edu/mstar) or email me at This email address is being protected from spambots. You need JavaScript enabled to view it..

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We Have Moved!

New location 710 Westwood Plaza, Room C-224, Los Angeles, CA 90095

As of January 1st, 2016, the Mary S. Easton Center for Alzheimer’s Disease Research at UCLA has officially moved back on the UCLA campus. We are now located in the Reed Neurological Research Center building at 710 Westwood Plaza, Room C-224, Los Angeles. The main office is in close proximity to the rest of the Department of Neurology, and directly across from the Ronald Reagan UCLA Medical Center. The bi-weekly Caregiver Support Group will remain at the Weyburn location until the end of February. If you would like more information, please call our main office at (310) 794-3665 or visit our website at www.eastonad.ucla.edu.

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Clinical Research Opportunities

If you would like to advance Alzheimer's disease research, please consider participating at the Easton Center. Below are two current trials. For a complete list of enrolling studies, visit our website at www.eastonad.ucla.edu.

The Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease (A4) Study:

The A4 Study is a clinical study for older individuals (ages 65-85) who have normal thinking and memory function but who may be at risk for developing Alzheimer's disease (AD) memory loss sometime in the future. The A4 study is for people without any outward signs of Alzheimer's disease, and is designed to evaluate the effectiveness, safety and tolerability of an investigational drug for AD. The purpose of the Anti-Amyloid Treatment in Asymptomatic Alzheimer's study (the "A4 study" for short) is to test whether a new investigational treatment can slow the memory loss caused by Alzheimer’s disease. The overall goal of the A4 study is to test whether decreasing amyloid with antibody investigational treatment can help slow the memory loss associated with amyloid buildup in some people. The A4 Study lasts for three years, and participants will be assigned at random to receive either the investigational drug or a placebo and will be monitored over that period.

In general, you may be eligible to join the A4 Study if you:

  • Are 65 to 85 years old
  • Have normal thinking and memory abilities
  • Have a study partner (someone who has weekly contact with you and is willing to answer questions once a year).

If you are interested in participating, please call (310) 794-6191 or visit www.eastonad.ucla.edu.

Study of A Beta Secretase Inhibitor in Prodromal Alzheimer's Disease:


The Easton Center is currently participating in a Phase III clinical trial sponsored by Merck & Co of the investigational drug MK-8931. MK-8931 reduces levels of the beta amyloid protein by inhibiting the activity of an enzyme called beta secretase. MK-8931 is an oral medication taken daily. The study is approximately two years long, with roughly 12 study visits. Participants will be randomly assigned to the active study medication (MK-8931) or placebo. A placebo is a pill that looks just like the active medication but has no biological activity. Participants will have a 66% chance of receiving the active study medication. Individuals age 50-85 who have a memory problem are potentially eligible for this study. If you are interested in participating, please call (310) 794-6191 or visit www.eastonad.ucla.edu.

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Upcoming Event

Architects of Change Conversation with Seth & Lauren Rogen
Date: Wednesday, February 24th, 2016
Time: 7:00 P.M. - 8:00 P.M.
Location: UCLA Anderson School of Management
Korn Convocation Hall - 110 Westwood Plaza, Los Angeles, CA 90024

Seth and Lauren Rogen, founders of Hilarity for Charity, and Maria Shriver will discuss the power of caregiving and how to engage young Americans in the fight against Alzheimer's.
For more information or to register, please CLICK HERE.

Caregiver U: A Morning to Take Care of You!
Date: Saturday, February 27th, 2016
Time: 9:00 A.M. - 12:30 P.M.
Location: Ken Edwards Center, 1527 4th Street, Santa Monica, CA

Verna Porter, M.D., F.A.N.A., Director of Clinical Programs, Mary S. Easton Center for Alzheimer's Disease Research at UCLA will present "Latest Treatments and Interventions in AD" at 10:00 A.M.
This is a FREE community event for family and working caregivers! To register, please call (800) 516-5323. CLICK HERE to view the flyer.

Dementia with Lewy Bodies
Date: Tuesday, March 1st, 2016
Time: 11:30 A.M. - 12:30 P.M.
Location: Webinar

Join UCLA Neurologist Sarah Kremen, M.D., as she discusses the symptoms, diagnosis and management of dementia with Lewy bodies, a type of dementia that causes a progressive decline in mental abilities due to abnormal microscopic deposits that damage brain cells over time. This neurodegenerative disease is the second most common progressive dementia after Alzheimer's disease.
Register for the webinar » CLICK HERE.

Early Memory Loss Forum
Date: Sunday, April 10th, 2016
Time: 9:00 A.M. - 3:30 P.M.
Location: Skirball Cultural Center, 2701 N Sepulveda Blvd, Los Angeles, CA 90049

Edmond Teng, M.D. Ph.D., Co-Director, Katherine and Benjamin Kagan Alzheimer's Disease Treatment Development Program will present "The Latest Research Developments" at 1:15 P.M.
A one day, interactive symposium created by and for people with early stage Alzheimer's disease and related disorders. The conference provides support, education and networking for the special needs of those with early stage dementias.
Please call (844) 435-7259 for more information, or CLICK HERE to register online.


Our mailing address is:
Mary S. Easton Center for Alzheimer's Disease Research at UCLA
710 Westwood Plaza, Room C-224
Los Angeles, CA 90095-1769
http://www.eastonad.ucla.edu | Phone Number: (310) 794-3665 / Appointments: (310) 794-6039
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Copyright © 2016. Mary S. Easton Center for Alzheimer's Disease Research at UCLA. All rights reserved.

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