The Mary S. Easton Center for Alzheimer’s Disease Research at UCLA has very active teams working on basic research, drug discovery, biomarkers for early diagnosis and clinical activity including clinical trials, cognitive testing, and patient care. [PDF Version]
Using Genetics to Help Patients with Alzheimer’s Disease
By: Dr. Darice Wong, Dr. Jessica Rexach, Dr. Varghese John, Dr. Gal Bitan, Dr. Sarah Kremen, and Dr. Brent Fogel
Patients struggling with the onset of memory loss face many challenges. People commonly ask “Why did this happen?”, a question that can be difficult for doctors to answer. Recent advances in technology have improved the ability to identify genetic causes of memory loss, particularly when it affects, or could affect, other family members.
At UCLA, we have experts in Neurogenetics, a field of Neurology that studies the genetic basis of disease. Neurogeneticists specialize in seeing patients and families with high risk of Alzheimer’s disease to provide them and their doctors with additional information to help guide medical assessments and diagnostic testing. Genetic counselors work alongside neurogeneticists to help patients and families understand how the information in their DNA can lead to memory loss.
DNA is the hereditary material that serves as a blueprint for a person’s growth, development, and other characteristics. Genes are sections of DNA that code for particular features, such as eye or hair color, but in some cases, genes can become damaged and cause disease. A person’s entire set of genes is called their genome.
Alzheimer’s is a heritable disease, though the genetics are not the same for all people who experience the disease. For people with early-onset Alzheimer’s, defined as under the age of 65 and typically affected in the fourth or fifth decade of life, the disease is commonly determined by a single gene mutation. Such cases make up only a small portion of Alzheimer’s disease, generally less than 1% of cases. For late-onset Alzheimer’s, which is the most common type, there is not one specific gene that causes the disease; instead there are many genes that may contribute to increasing a person’s risk for developing Alzheimer’s. The most well-known of these genes is the APOE gene, of which the ApoE4 form confers the most risk; it can increase one’s risk for developing Alzheimer’s disease between 4 to 12 times. However, this knowledge alone is not sufficient to predict whether someone will develop Alzheimer’s disease during their lifetime.
For individuals with Alzheimer’s disease, we can perform tests for some of the genetic factors that contribute to their disease. For early-onset Alzheimer’s our current tools for genetic testing are highly accurate at diagnosing and predicting disease caused by single genes. Single gene mutations are even more frequent in a clinically-similar disorder, frontotemporal dementia, and can help distinguish between the two diseases and guide treatment. In such cases, determining which of several known memory genes, if any, is contributing to a patient’s memory loss can clarify the diagnosis, ensure optimal management, establish family risk, and align patients with additional resources for support, research, care and planning.
Our goal is to empower our patients and their families with the most scientifically accurate information, resources, care and support they need to optimally navigate these challenging disorders both now and in the future. As an academic center, we also work every day to fill-in the key knowledge gaps for a better future where we can both diagnose and effectively treat all patients at risk for these disorders.
UCLA has pioneered the use of genomic technology in patient diagnostics and research, and UCLA Neurology has been one of the leaders in the application of genomics to neurological disease, both clinically and in research investigating possible causes of disease. Discovering this has created important opportunities for medical researchers to learn about what happens in the brain that triggers Alzheimer’s disease, and could one day lead to new therapies and potentially even cures. For most cases of Alzheimer's disease, multiple genetic factors work together to determine “risk”, or the chances of developing memory loss. Physicians and researchers are working to develop genetic “scores” to identify people at the highest risk for Alzheimer’s disease. Our current ability for accurately predicting Alzheimer’s disease based on genetic profiles is still in its infancy but we are learning more every day and every patient with Alzheimer’s disease can help us learn more! By studying the DNA of many patients with Alzheimer’s disease, researchers can help uncover the keys to predicting which people might get the disease and when.
Our Department has recently launched the Clinical Neurogenomics Research Center (CNRC). The goal of the CNRC is to bring genomic diagnostic and research advances to all UCLA patients with neurological disease, in synergy with the system-wide efforts of the UCLA Institute for Precision Health. The Center provides a resource for all department physicians to contribute to and engage in genomic-based research on neurological disease from rare neurogenetic conditions to more common or complex neurological disorders, such as Alzheimer’s disease. The CNRC allows neuroscientists both within and outside of UCLA Neurology to address research questions across the spectrum of neurological disease through our collection of genomic and clinical data as well as samples collected from patients representing a broad range of ages, genders, races, ethnicities and brain disease diagnoses. It also allows patient participation to contribute not only to research on their own diagnosis, but to research on all neurological diagnoses.
Looking for Drug Targets
The Drug Discovery Lab (DDL) at the Mary S Easton Center for Alzheimer's Disease Research at UCLA is led by Dr. Varghese John, a professor in the UCLA Department of Neurology. His team develops therapeutic candidates for clinical testing in AD. This drug discovery effort is dependent on the identification of new targets and mechanisms involved in AD pathogenesis. One of the targets they are looking for is Sirtuin-1 (SirT1). Sirtuin-1 levels in the brain and plasma are known to be reduced in AD especially in ApoE4 carriers. As part of an NIH grant titled "ApoE4-targeted therapeutics that normalize SirT1" his team has identified a small molecule that increases SirT1 levels in mice and improves memory. For the preclinical development of this molecule, they are interested in looking at SirT1 levels in human blood samples for future use in clinical testing of this drug candidate.
Searching for Blood Biomarkers to Improve Diagnosis
The Bitan Lab in the Department of Neurology, led by Dr. Gal Bitan, a professor in the UCLA Department of Neurology, has been working with the Clinical Neurogenomics Research Center for the past two years. His team is extremely grateful for the work that the CNRC does; getting the blood samples his team needs would be much more difficult without the CNRC. The researchers in the Bitan Lab are also grateful to the patients and healthy persons who donate blood through the CNRC.
The researchers are working on developing novel blood tests for different neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and several other dementias, movement disorders, and neuromuscular diseases. These UCLA researchers are studying blood exosomes, small packages released by cells into the bloodstream that travel between cells in the body. Exosomes contain DNA, RNA, and other materials that can be used to detect markers of disease. The blood samples collected from patients and healthy persons serve two purposes for the Bitan Lab. First, every test that is developed must be characterized thoroughly and rigorously, and for this characterization, the team needs relatively high volumes of blood so they can repeat the test multiple times and verify that it is sensitive, stable, and reproducible. Second, the team uses smaller blood samples to compare between patients and healthy people, patients with different diseases, and patients who donate blood at different times during the disease. This enables the researchers to develop sensitive diagnostic tests and tests that can report on the level of disease progression in the brain without actually having to do a brain scan or a spinal tap. The ability of the CNRC to provide all of these blood samples is an invaluable asset for their research!
Learn more about the Clinical Neurogenomics Research Center, including how to become a research participant, by visiting our website https://www.uclahealth.org/neurology/cnrc/research or by leaving a message and your contact information at (310) 825-2320.
For information regarding clinical evaluations, please call the UCLA Neurology Clinic at (310) 794-1195.
Celebrating the Holidays Safely with Someone with Dementia
By: Monica Moore, M.S.G.
The hustle and bustle of the holiday season is upon us. From the parties, to shopping, to family gatherings, this time of year can be filled with excitement and activities, yet for a person with dementia this could lead to increased confusion, anxiety and disrupted behavior. The increase in these challenging behaviors can lead to increased stress for the family caregiver. Below are a few tips to ensure your loved one stays safe this holiday season and that the holidays are merry and bright for you, the caregiver.
Prepare the person with dementia. Explain who will be coming to events and what the event is and why it is important. Plan and rehearse activities that will keep your loved one engaged even if they are not able to follow along in conversation. Use name tags to reduce confusion and anxiety to remember.
Prepare friends and family members. If it has been some time since your friends and family members have seen your loved one with dementia fill them in on the progression that has occurred over that time, explain what the person with dementia can or cannot do and when they may need supervision or assistance.
Make home safe. Tone down decorations, be careful about rugs, lights, and other holiday decorations. Create a quiet place away from guests where the person with dementia can retreat for some quiet or a rest.
Travel wisely. When traveling over the holidays, ensure that your loved one with dementia has identification such as bracelets, tracking devices, or clothing labels. If you are flying, tell the flight crew that the person you are traveling with has memory problems and might need some extra time and assistance. Airports are at their busiest this time of year, so never allow your loved one out of your sight. Carry identification that alerts others to the fact that you are a caregiver of someone with dementia in case you fall ill or are injured.
While the holidays are supposed to be a time of joy, they can also be a time of sadness. If you find yourself overwhelmed seek professional support. The Alzheimer’s Association has a telephone helpline that is available free of charge 24 hours a day 365 days a year, so please call (800) 272-3900 and find someone to talk to.
Thank You for Making a Difference!
The prevalence of Alzheimer's disease (AD) doubles every five years beyond age 65 and more than 1/3 of people over 85 have Alzheimer’s or a related dementia. This increase in Alzheimer’s disease will substantially increase with the aging of the US population. Termed the “silver tsunami”, as the Baby Boomers age, the prevalence in Alzheimer’s disease is expected to sharply increase. The popular press often speaks of “living well into the 100’s” but our lifespan will not meaningfully increase if the problems of Alzheimer’s disease and brain aging are not solved. Many of the world’s leading physician-scientists are working at the Mary S. Easton Center at UCLA on just that.
Along with treating some of the most complicated cases of AD, we conduct genetic studies, basic research into disease pathways and progression, and rapid translation of discoveries and ideas into novel treatments from our drug discovery lab and clinical trials. The proximity and synergy between clinical medicine and basic science puts UCLA in a unique position to solve Alzheimer's disease. Some of the basic research studies in Alzheimer’s disease include:
Characterizing the amyloid beta (Aß) protein: this research focuses on characterizing the subcellular interactions of the amyloid beta (Aß) protein, considered by most to be the proximate cause of AD.
Design and development of structure-based small molecule inhibitors of amyloid assembly to prevent the accumulation of Aß: these studies develop new compounds that inhibit the formation of toxic protein aggregates that cause AD, including those of Aß and tau.
The generosity of our donors allows the Mary S. Easton Center for Alzheimer's Disease Research at UCLA to honor its commitment to:
improve the quality of life for patients through compassionate care
support psycho-social needs of AD families and caregivers
develop new medications and treatments for Alzheimer's disease and related conditions
continue the relentless pursuit of a cure
We would like to express our gratitude to the supporters of the Mary S. Easton Center. Your philanthropy truly makes an impact on our progress and ongoing research.
Clinical Research Opportunities
If you would like to advance Alzheimer's disease research, please consider being a study participant. Below are the current recruiting trials. For a complete list of enrolling studies, visit our website at www.eastonad.ucla.edu.
EASTON CENTER KAGAN CLINICAL TRIALS PROGRAM
- Alzheimer's Disease Neuroimaging Initiative 3 (ADNI3) Protocol
- NEAT (Nicotinamide as an Early Alzheimer's Disease Treatment) Study
BEHAVIORAL NEUROLOGY PROGRAM
- Curcumin and Yoga Therapy for Those at Risk for Alzheimer's Disease
- Effect of Grapes Dietary Supplement on Brain Metabolism and Cognition
- The UCLA Caregiver Sleep (CARES) Study
For information on other upcoming lectures and events, please visit the Easton Center Community Calendar.
Holiday Tips for Caregivers
Date: Tuesday, December 17, 2019
Time: 1:00 P.M. – 2:30 P.M. (PST)
Location: Malibu Senior Center
23825 Stuart Ranch Road
Malibu, CA 90265
Presenter: Monica Moore, M.S.G.
The holidays can be a stressful time for caregivers. We have 10 tips to help make the holidays a more pleasant time for all. Learn ways to prepare for a more enjoyable holiday season with your loved one.
Update on Alzheimer’s Disease Research [CANCELED]
Date: Friday, January 31, 2020
Time: 11:00 A.M. – 12:30 P.M. (PST)
Location: UCLA Marisa Leif Conference Room
300 Medical Plaza, 3rd Floor, Room 3200
Los Angeles, CA 90095
Presenter: Sarah Kremen, M.D., Clinical Physician of Neurology, David Geffen School of Medicine at UCLA will be giving an update on Alzheimer’s Disease research. RSVP required - please call (310) 794-3914.
Alzheimer’s Disease Basics
Date: Wednesday, February 12, 2020
Time: 10:30 A.M. – 11:30 A.M. (PST)
Location: Freda Mohr Senior Center
6310 San Vicente Boulevard, #275
Los Angeles, CA 90048
Presenter: Monica Moore, M.S.G.
Alzheimer’s Disease is the most common form of dementia, currently affecting 5.3 million Americans. Come learn more about this disease, who it most commonly affects, and the latest treatments and medical options.
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 / Clinic Appointments: (310) 794-1195 |
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