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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]
"This article is the first in a series entitled "Why I Participate," which will focus on involvement in our research and programs through clinical trials, support groups, and donations."
About 3 years ago my wife got into a conversation with the daughter of our best friends. The daughter, you see, had graduated with a Masters in Gerontology and gotten a job with UCLA working on the A4 Alzheimer's study. (editor's note: study no longer recruiting, visit www.eastonad.ucla.edu for a list of actively recruiting studies). During the course of that conversation, the daughter asked my wife if she would like to be tested to see if she was a possible candidate to test a drug that they hoped might alleviate some Alzheimer's symptoms.
My wife readily agreed to being tested and soon the consent paperwork was emailed for her signature. At this point my wife asked if I would also like to be considered, but due to a recent heart attack, I thought it would be very unlikely that I would be a suitable candidate. I did want to support my wife because to me this sounded like a very worthwhile cause and anything we could do to help find a possible cure for Alzheimer's was certainly worth doing. So, with that in mind, off we went to UCLA Medical Center for a full day of testing.
Several weeks later we were asked to report to UCLA for the test results. The doctor made us comfortable in her office and started with my wife's folder. She thanked us for taking the time to volunteer, drive all the way from the South Bay up the 405 and consenting to be tested. Unfortunately, the doctor told my wife, my wife's brain did not have the level of plaque they were looking for so she was not a suitable candidate. Well, I thought, that's too bad -- and now we will pack it in and drive back home knowing that we tried but failed to qualify.
At that point the doctor looked me straight in the face and said "But your husband is perfect!" My mouth fell open and I almost fell off the chair. It never occurred to me that I would be chosen and not my wife. When the doctor asked if I wanted to participate I almost shouted "Heck YES!" and at that exact moment I became a UCLA "lab rat" and have never regretted it since.
Once each month I make my way up to UCLA where I get my vital statistics (weight, blood pressure and temperature) taken and am then escorted to a room with a bed complete with wonderful heated blankets. I feel like I'm getting the VIP treatment each time. Next, one of the study doctors stops by to inquire about my health, if any of my medications have changed and how I'm feeling. After the doctor gives me the green light to receive my infusion, a nurse installs a needle in my arm and then goes to the pharmacy to get my IV bag which may contain the drug being tested or a placebo.
It's a double-blind study so only the drug manufacturer knows exactly what I'm getting. The infusion takes only about 20 to 30 minutes and sometimes I do computerized cognitive testing while relaxing under my warm blankets. Since I've been doing this routine for the last 20 months I've gotten to know most of the doctors, nurses and staff involved in the study and they are fun to talk to.
So, since I'm retired why do I take one day a month out of my life to drive up to UCLA in heavy traffic, spend most of a day getting poked, prodded, tested (both mentally and physically), analyzed, injected and screened for no monetary reward? Well, I guess the short answer is that this is important and someone has to do it.
But a better answer is that Alzheimer's is simply an awful disease and anyone who has a family member or friend that currently has or has died from Alzheimer's knows just how terrible it truly is. Anything, absolutely anything, I can do to help in finding a cure I'm going to do. That's why I became a UCLA lab rat. It's as simple as that.
Figure legend: Composite structure showing 3 different aggregation surfaces on the VQIINK segment. Residues from four different strands (colored in cyan, green, yellow, and magenta) come together to form a tightly interdigitated amyloid-like structure. An inhibitor (shown in orange) targets the structure shown by binding to the tip, thereby halting its ability to grow, and to seed new fibrils.
The aggregation of tau protein into amyloid-like inclusions called neurofibrillary tangles is a histological hallmark of Alzheimer's disease (AD), and dozens of related dementias called tauopathies. Cognitive decline is associated with the accumulation and spreading of tau aggregates in the brain, and evidence suggests that aggregated tau is transmitted throughout the brain by transfer along anatomical connections. Amplification of aggregated tau is thought to occur by a process known as "seeding", whereby pre-existing tau fibrils serve as templates to promote the conversion of new fibrils from pools of nonpathological tau monomer.
The David Eisenberg Laboratory at UCLA is collaborating with Harry Vinters' Laboratory at UCLA to test the power of their newly devised panel of tau inhibitors for blocking the seeded spread of tau aggregates extracted from autopsied brain tissue of patients with various tauopathies including Alzheimer's disease, Progressive Supranuclear Palsy (PSP), Frontotemporal Dementia (FTD), Corticobasal Degeneration (CBD), Picks disease and Chronic Traumatic Encephalopathy (CTE). Both, Eisenberg and Vinters labs are also working with the Cole and Frautschy Laboratory at the Mary S. Easton Center for Alzheimer's Disease Research at UCLA to evaluate the efficacy of the inhibitors in a tau mouse model, and to develop ways of delivering the inhibitors to the brain.
Over the last decade, the Eisenberg Lab has focused on determining the atomic structures segments from tau protein that drive aggregation, and on the design of inhibitors to suppress tau aggregation. In 2007 the Eisenberg Lab determined the structure of the first tau aggregation-driving segment with the amino acid sequence VQIVYK (Sawaya et al., Nature (2007)). This structure allowed the researchers to design the first structure-based inhibitors of tau aggregation, which works by capping the ends of tau fibrils to prevent further growth (Sievers et al., Nature (2011)).
In work published this year, Paul Seidler, a postdoctoral fellow in the Eisenberg Lab and awardee of an Alzheimer's disease grant that is co-sponsored by Alzheimer's Greater LA and The BrightFocus Foundation, reported that the Eisenberg Lab had extended their arsenal of tau inhibitors to include the other known aggregation-driving segment in tau with the amino acid sequence VQIINK. The sub-micron scale of the crystals of VQIINK had presented a decade-long barrier to structure determination. Fortunately, recent methodological advances in cryo-electron microscopy and micro-electron diffraction (MicroED) allowed the team to determine the atomic resolution structure of this segment in collaboration with the lab of Tamir Gonen at UCLA. Unexpectedly, the Eisenberg team discovered from this structure that multiple surfaces of the VQIINK segment help to drive tau aggregation, and that inhibitors targeting these aggregation-prone surfaces blocked the seeded spread of aggregated tau (Seidler et al., Nature Chemistry (2017)).
Our team of researchers at UCLA, who have expertise in structural biology, pathology and mouse models of neurodegeneration, aim to discover whether tau aggregates from different tauopathies respond to the same types of inhibitors, which target specific regions of tau, or whether different tauopathies exhibit unique fingerprints of specificity. Using this inhibitor profiling approach, we hope to be able to characterize brain- derived fibrils from different tauopathies in order to discover how closely related aggregates from these diseases are, and which inhibitors from our panel are most effective at blocking the pathological spread of tau in each of these diseases.
Please join us in welcoming two new members to the Easton Center's Neuropsychology Program.
Photo: Heleya Rad, Psy.D.
Dr. Heleya Rad is a clinical neuropsychologist in the Neuropsychology Program at the Easton Center. She completed her graduate training at Pepperdine University and her predoctoral internship at NYU Langone Medical Center, Rusk Rehabilitation, where she specialized in the provision of cognitive remediation. She completed her postdoctoral fellowship in Neuropsychology at Harbor-UCLA Medical Center.
Her clinical practice includes the provision of neuropsychological services to Farsi-speaking individuals. Dr. Rad has a special interest in the unique and culturally rooted needs of the underserved Iranian population.
Dr. Rad serves as a clinical neuropsychologist in the Neuropsychology Clinic of the Department of Neurology. In her role, she supervises predoctoral externs and postdoctoral fellows in the practice of neuropsychology. She also serves as a clinical trials rater at the Easton Center and a Volunteer Clinical Instructor in the Department of Psychiatry and Biobehavioral Sciences. We are excited to welcome Dr. Rad to our team!
Photo: Kaitlyn Kauzor, M.A.
Kaitlyn has recently joined the Mary S. Easton Center as a member of the Cognitive Neuropsychology Lab. She received her M.A. in Clinical Psychology from Cal State Northridge (CSUN). During her undergraduate and graduate education, Kaitlyn worked as a lab coordinator for a Neuropsychology and Dementia research lab, studying the effects of degenerative disease on older adults' cognitive and functional capacity. Kaitlyn is thrilled to be a part of the research being done here at UCLA studying Alzheimer's disease. She will be utilizing the knowledge and skills gained from these experiences to continue on to her doctoral work in the Fall.
If you would like to advance Alzheimer's disease research, please consider participating at the Easton Center. 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
- ENGAGE (221AD301 Phase 3 Study of Aducanumab (BIIB037) in Early Alzheimer's Disease) Study
- NEAT (Nicotinamide as an Early Alzheimer's Disease Treatment) Study
- SUVN-502 Study with Donepezil and Memantine for the Treatment of Moderate Alzheimer's Disease
BEHAVIORAL NEUROLOGY PROGRAM
- Early-onset Alzheimer's Disease Phenotypes: Neuropsychology and Neural Networks
- Neuropsychological Test Measures in Behavioral Variant Frontotemporal Dementia (bvFTD) and Healthy Subjects
- Curcumin and Yoga Therapy for Those at Risk for Alzheimer's Disease
- E2609 Study for MCI and Early Alzheimer's Disease (MissionAD1)
- Effect of Grapes Dietary Supplement on Brain Metabolism and Cognition
- The UCLA Caregiver Sleep (CARES) Study
Latest News, Hot Topics and Updates from Alzheimer's Association:
2018 Alzheimer's Disease Facts and Figures
Includes a Special Report on the Financial and Personal Benefits of Early Diagnosis [PDF]
For information on other upcoming lectures and events, please visit the Easton Center Community Calendar.
23rd Annual UCLA Research Conference on Aging
Date: Wednesday, May 16, 2018
Time: 8:00 A.M. - 12:30 P.M. (PDT)
Location: Ackerman Grand Ballroom
308 Westwood Plaza
Los Angeles, CA 90095
The event provides opportunities for researchers and community members to network, be apprised of the latest research across a broad range of topics including aging biology, epidemiology, clinical research in older adults, public health, and health policy, and to spark new and innovative collaborations. The program includes one keynote lecture, two poster sessions, and plenary talks. http://geronet.ucla.edu/rcoa
South Bay Dementia Education Consortium presents Spirituality and Alzheimer's Disease
Date: Tuesday, June 5, 2018
Time: Reception 12:00 P.M. - 4:00 P.M. (PDT)
Location: Redondo Beach Main Public Library
303 N. Pacific Coast Hwy., 2nd Floor
Redondo Beach, CA 90277
Please RSVP by phone at (310) 374-3426 x256.
Alzheimer's Greater Los Angeles presents Caregiver Wellness Day San Fernando Valley
Date: Friday, June 22, 2018
Time: 10:00 A.M. - 1:00 P.M. (PDT)
Location: Zev Yaroslavsky Family Support Center
Van Nuys, CA 91405