Genetics of Aging-Related Neurodegeneration: The Sylvan M. Cohen Annual Retreat & Poster Session 2017

077On Tuesday, May 23, 2017, the Institute on Aging (IOA) hosted their annual Sylvan M. Cohen Retreat and Poster Session in collaboration with co-sponsors, the Penn Neurodegeneration Genomics Center (PNGC).

The 2017 retreat focused on the ‘Genetics of Aging-related Neurodegeneration’ and for the second year in a row, it began with opening remarks from the Dean of the Perelman School of Medicine, J. Larry Jameson, MD, PhD. “I’m mainly here to thank you for your scientific collaboration,” said Dean Jameson. He used this time to express the importance and impact of these contributions in the field of genetics and aging, especially in trying to solve the puzzle of very complex conditions such as neurodegeneration.

Lectures were presented by Penn’s Gerard (Jerry) D. Schellenberg, PhD, Director of the PNGC, Adam Naj, PhD, Assistant professor of Epidemiology in Biostatistics and Epidemiology, and Nancy Zhang, PhD, Assistant professor of Statistics, as well as this year’s keynote speaker, Philip De Jager, MD, PhD, Associate Neurologist at Brigham and Women’s Hospital and Associate Professor of Neurology at Harvard Medical School.

Lectures:

  • “Alzheimer’s Disease Genetics; Progress in Gene Therapy” – Jerry Schellenberg, PhD
  • “Genetic Risk Factors Associated with Coincident Alzheimer’s and Parkinson Disease in Neuropathologically Confirmed Cases” – Adam Naj, PhD
  • “Structural Variant Profiling in Alzheimer’s Disease Genetics” – Nancy Zhang, PhD
  • “The molecular network map of the aging cortex: v1.0: an integrative approach targets the epigenomic and inflammatory components of Tau pathology” – Philip De Jager, MD, PhD

As usual, the event concluded with the annual poster session on aging. Prizes were awarded to the top posters in each of the following categories: Basic Science and Clinical Research/Education & Community.

Poster Winners:

BASIC SCIENCE:

1st Place:

172Title: “Integrative analysis identifies immune-related enhancers and IncRNAs perturbed by genetic variants associated with Alzheimer’s disease”
Presenter: Alexandre Amlie-Wolf
Authors: Alexandre Amlie-Wolf, Mitchell Tang, Jessica King, Beth Dombroski, Elizabeth Mlynarski,Yi-Fan Chou, Gerard D. Schellenberg, Li-San Wang
Affiliation(s): University of Pennsylvania, Genomics and Computational Biology Graduate Group

2nd Place:

173Title: “Differential Vulnerability to a-synuclein Pathology Among Neuronal Subpopulations”
Presenter: Luna Esteban
Authors: Luna Esteban, Dawn M. Riddle, Virginia M.Y. Lee, Kelvin C. Luk
Affiliation(s): Center for Neurodegenerative Disease Research

 


Clinical Research/Education & Community

1st Place:

175Title: “Correlates of Sleep Indices Among Community Dwelling Older Adults Enrolled in a Collaborative Care Management Program”
Presenter: Ashik Ansar
Authors: Ashik Ansar, MD, PhD, Shahrzad Mavandadi, PhD, Kristin Foust, Suzanne DiFilippo, RN, Joel E.. Streim, MD, David W. Oslin, MD
Affiliation(s): Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania

2nd Place:

176Title: “The Impact of Cognitive Reserve and Brain Atrophy on Survival in Neurodegenerative Diseases”
Presenter: Carrie Caswell
Authors: Carrie Caswell, MS (1), Sharon X. Xie, PhD (1), Murray Grossman, MD, EdD (1), Corey T. McMillan, PhD (1), Lauren M. Massimo, PhD, CRNP (1,2)
Affiliation(s): (1) University of Pennsylvania, (2) Penn State University

To view the full lectures from the 2017 Sylvan M. Cohen Annual Retreat, click here.

To view more photos from the 2017 Sylvan M. Cohen Annual Retreat, click here.

 

“Through the Eyes of the Caregiver: Frontotemporal Degeneration (FTD) and the Penn FTD Center” premieres at the Penn FTD Center Caregiver Conference 2017

On Friday, May 12, 2017, the Penn Frontotemporal Degeneration (FTD) Center hosted its 9th annual Penn FTD Caregivers Conference at the University of Pennsylvania. The day-long conference held at the Smilow Center for Translational Research welcomed 150 attendees and consisted of a series of lectures that covered information around the latest scientific advances in research on FTD and its related disorders, such as Amyotrophic lateral sclerosis (ALS) also known as Lou Gehrig’s Disease and Corticobasal degeneration (CBD), as well as practical caregiving issues such as strategies for symptom management, understanding the genetics of FTD and genetic testing options, respite and supportive resources for caregivers, and legal and long-term care planning.

One of the highlights of this year’s conference was the premiere of “Through the Eyes of the Caregiver: Frontotemporal Degeneration (FTD) and the Penn FTD Center,” a short film sharing the stories of three caregivers whose loved ones are patients at the Penn FTD Center.

“The brunt of this disease falls solely on those closest to the individual with the disease unfortunately and it is very difficult to navigate the healthcare system and obtain the types of resources that give structure to a patient’s day-to-day life and to help a caregiver keep a patient safe and cognitively stimulated,” said David Irwin, MD, assistant professor and Cognitive Neurologist in the Penn FTD Center. The goal of this video is to show caregivers and family members of those with FTD that they are not alone in this life-altering process and that there are many support groups and community and medical resources available to them – including many at the Penn FTD Center – to help them every step of the way.

Watch “Through the Eyes of the Caregiver: Frontotemporal Degeneration (FTD) and the Penn FTD Center”*:

Two Penn FTD Caregivers Conference sponsors, the Alzheimer’s Association Delaware Valley Chapter and the Association for Frontotemporal Degeneration (AFTD), were also in attendance to answer questions and present information on the many advocacy and community resources that they offer for patients with FTD or related disorders and their families and caregivers.

Learn more about the Penn FTD Center at: https://ftd.med.upenn.edu

* Learn more about each individual caregiver by watching their full story! Click the “i” icon bubble in the top right hand corner of the video for a drop down menu with links to each caregivers story! If you are watching on a mobile phone, click the title of the video which will open a drop down menu containing the links to each caregiver’s story as well as a link to the Virtual Tour of Penn’s FTD PPG and Penn FTD Center to learn more about the FTD research and care taking place at Penn.

The Longevity Dividend

On Tuesday, November 29, 2016, the Institute on Aging hosted its annual Vincent J. Cristofalo Lectureship and reception featuring this year’s keynote speaker, S. Jay Olshansky, PhD, professor of public health at the University of Illinois at Chicago.

Dr. Olshansky’s research focuses primarily on human longevity, exploring the health and public policy implications associated with individual and population aging, global implications of the re-emergence of infectious and parasitic diseases, and most recently, the topic of his Cristofalo Lecture; the pursuit of the scientific means to slow aging in people, or as he calls it “The Longevity Dividend.”

“The Longevity Dividend,” a term borrowed from the era of the “peace dividend,” is basically the idea that if we can find a way to slow the basic biological aging process, both society and individuals will reap huge economic and health benefits.

Over the years, human life expectancy has become longer but the success of extended lifespans come with a price. With the ridding of many infectious diseases came the rise of other conditions such as cardiovascular disease, cancer, and Alzheimer’s disease; three different diseases with one thing in common—the process of aging being their most powerful risk factor.

“The rise of these diseases are nota consequence of failure… they are a consequence of success. You’ve lived long enough to experience them. But, the consequences of success might be very dangerous.” – S. Jay Olshansky, PhD

Dr. Olshanksy shared more on the “longevity dividend” during our video interview here:

In addition to his current research on “The Longevity Dividend,” Dr. Olshansky and his colleagues have also conducted research on “facial analytics” combined with biodemography. The study of facial analytics uses components of the face to measure disease risk, longevity risk, and survival prospects. Through this research, Dr. Olshansky and his team are trying to find new ways of allowing organizations and industries to use what we know about ourselves to improve the ways that they do assessments of health and survival.

Recently, Dr. Olshansky and his colleagues published an article in Computer that lays out the framework for building a “health data economy.”

“I think a new form of “currency” will be developed and this “currency” will be your own health data,” explained Dr. Olshansky. The idea is to take data from Fit Bits and other wearable monitoring devices monetize this information, for instance, selling your recorded health data to companies and organizations in exchange for things like money, lower premiums on health insurance policies, coupons, and more. He believes that this resource could be the new form of collecting health data and could inspire a whole new generation of citizen scientists.

To watch Dr. Olshansky’s full lecture on “The Longevity Dividend,” click here.

To learn more about the Vincent J. Cristofalo lectureship, click here.

Developing Breakthrough Treatments for Alzheimer’s Disease

“Alzheimer’s disease (AD) is our #1 public health problem in terms of cost and burden of care and it is projected that over 100 million people will be diagnosed with Alzheimer’s worldwide by 2050,” said Stephen Salloway, MD, MS, a professor of Neurology and Psychiatry at Brown University and the Institute on Aging (IOA) at the University of Pennsylvania’s most recent Visiting Scholar.

On Tuesday, November 15, 2016, Dr. Salloway visited the University of Pennsylvania to present a lecture on “Developing Breakthrough Treatments for Alzheimer’s Disease” in which he shared some of the latest advances, and challenges, in the field of Alzheimer’s disease research.

“Our goal, and the goal of the National Plan developed by the U.S. Congress, is to develop breakthrough treatments by 2025.” – Stephen Salloway, MD, MS

It’s no secret that the world is getting older. In fact, according to Dr. Salloway, there are many regions of the world where more than 30 percent of the population will be 60 or older and coming into the risk state for cognitive impairment. Aside from the staggering and rising cost of care for Alzheimer’s disease and related dementias, it is the disease that older people fear most — fearing the disability and loss of identity.

With this in mind, you would assume that Alzheimer’s research would be a top priority, but “funding for Alzheimer’s disease at a federal level has paled in comparison to other diseases like cancer and heart disease,” said Dr. Salloway. However, things are starting to look up and we have recently started to see some improvement. For the first time, there is a strong potential for Alzheimer’s federal research funding to reach over $1 billion.

Researchers are steadily working to build a worldwide infrastructure to fight Alzheimer’s disease with a number of private/public partnerships, collaborative initiatives such as the Alzheimer’s Disease Neuroimaging Initiative (ADNI) one component of which is right here at Penn, and many other alliances across the board. We’ve already seen several important benefits emerge from these initiatives; for example, real time data sharing to trigger an increase in publications and shape new trials and views on Alzheimer’s research.

Several advances in AD research have been made over the years, from the discovery of plaques and tangles to the development of new imaging techniques and biomarker breakthroughs. “We now know that plaques and tangles begin accumulating 15-20 years before the onset of cognitive decline,” explained Dr. Salloway. Through these findings, we are able to better understand the progression of Alzheimer’s disease as a process starting with a long pre-clinical period, moving on to an early symptomatic period of mild cognitive impairment (MCI), then followed by the actual dementia period. The significance of understanding this process is that it opens the door of opportunity to eventually intervene before a patient reaches the late stage of Alzheimer’s disease.

In terms of current treatments, there are two classes of medications approved to treat the symptoms of the dementia phase of Alzheimer’s disease—cholinesterase inhibitors and memantine. Both drugs have been found to have a very mild multi-symptomatic clinical effect, but cannot cure the disease or stop it from progressing, which is the ultimate aim for researchers.

Since 2003, there have been no new treatments approved by the U.S. Food and Drug Administration (FDA), but there have been several clinical trials focusing on the amyloid pathway — some disappointing and some encouraging.

Two major phase-3 trials were the bapineuzumab trial and the solanuzumab trial. While the bapineuzumab trial was stopped after showing no clinical benefit, the solanuzumab trial raised some hope after findings showed some modest slowing of cognitive decline in a milder subgroup. We are expecting to see some new results soon from a replication trial.

Most recently, some very encouraging results emerged from a phase 1b trial focusing on the antibody, aducanumab. This study showed a substantial dose-dependent lowering of a-beta on amyloid PET scans and also suggested dose-dependent lowering of cognitive decline. There are currently two phase-3 trials underway hoping to reproduce these findings in early Alzheimer’s disease.

“This is very exciting to enter the era of Alzheimer’s prevention, but there are many challenges,” said Dr. Salloway. One of the biggest challenges that researchers face is recruitment of a much larger sample size and population than they’ve used in the past. “In the past, we have tested medicine for people who are cognitively impaired, mostly with dementia, and now we have to reach people who may be at risk for Alzheimer’s in a community who is not coming specifically for care,” he explained. This means they will need hundreds of thousands, if not millions, of people to be enrolled in order to find the highest group at risk and to test medications.

For Dr. Salloway, trying to figure out how to reach and engage this community “is a vastly new undertaking and a second career.” However, he believes that a big avenue is going to be through all types of media—social media, print media, broadcast media, etc.

“The media is critical for getting the word out” – Dr. Salloway

Following the publication and coverage of the results of the aducanumab trial, Dr. Salloway’s center had over 500 calls from people looking to volunteer for research.

In terms of future research, Dr. Salloway has a vision. Through the eventual use of combination treatments and therapies, “Alzheimer’s disease will be much more treatable and manageable than it is today,” he believes.

“Our goal is to detect risk, initiate treatments early, engage the public, develop new public/private partnerships, and to make investments in research to succeed [in fighting Alzheimer’s disease].” – Dr. Salloway  

Dr. Salloway is also the Director of Butler Hospital’s Memory and Aging Center.

“To sleep, per chance to age… and avoid Alzheimer’s disease”: A recap of the 2016 Sylvan M. Cohen Annual Retreat

On Wednesday, June 8, 2016, the Institute on Aging hosted its annual Sylvan M. Cohen Retreat and Poster Session. This year’s retreat, titled “To sleep, per chance to age… and avoid Alzheimer’s disease,” was co-sponsored by Penn’s Center for Sleep and Circadian Neurobiology and explored the effects of sleep loss and it’s possible link to Alzheimer’s and other neurodegenerative conditions.

corrected_DJquoteAs usual, the event began with lunch and a series of lectures, but this year we had the pleasure of having J. Larry Jameson, MD, PhD, dean of the Perelman School of Medicine (PSOM), join us for opening remarks.

He expressed his excitement to see such collaboration amongst the two sponsoring centers and encouraged more of this, not only in the PSOM, but also across the University as a whole. “One of the secrets at Penn Medicine is that we have these catalytic centers and institutes and it’s even more impressive that there is often cross fertilization between them,” explained Dean Jameson.

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Keynote speaker, David M. Holtzman, MD, professor and chairman, Department of Neurology at Washington University School of Medicine, kicked off the lectures by discussing his research in “Understanding the Relationships between Sleep, Protein Aggregation, and Alzheimer’s disease.”

Other topics, covered by our Penn Presenters, included (click for video interviews):

Immediately following the lectures, researchers from the University of Pennsylvania and beyond presented their current aging-related work at our annual Poster Session. Categories included basic science, clinical research, & education and community and awards were given to the top posters.

Poster Winners

BASIC SCIENCE

1st Place
BasicSciecne1Enhancing a WNT-telomere feedback loop restores intestinal stem cell function in a human organotypic model of dyskeratosis congenita
Presenter: Dong-Hun Woo
Authors: Dong-Hun Woo, Qijun Chen, Ting-Lin B. Yang, M. Rebecca Glineburg, Carla Hoge, Nicolae A. Leu, F. Brad Johnson, and Christopher J. Lengner

 

2nd Place
BasicSciecne2AB Plaques Mediate Neuritic Plaque-like Tau Pathology that is Distinct from Perikaryal Tau Inclusions
Presenters: Zhuohao He
Authors: Zhuohao He, Jing L. Guo, Jennifer D. McBride, Lakshmi Changolkar, Bin Zhang, Ronald J. Gathagan, Hyesung Kim, Sneha Narasimhan, Kurt R. Brunden, John Q. Trojanowski, Virginia M.-Y. Lee


CLINICAL RESEARCH and EDUCATION & COMMUNITY *

1st Place
ClinRes1Tau Pathology Influences Dementia Onset and Survival in Lewy Body Spectrum Disorders
Presenter: David Irwin
Authors: David J. Irwin, MD MSTR, Murray Grossman MD, Daniel Weintraub MD, Howard I. Hurtig MD, John E. Duda MD, Sharon X. Xie PhD, Edward B. Lee MD PhD, Vivianna M. Van Deerlin MD, PhD,Oscar L. Lopez MD, Julia K. Kofler MD, Peter T. Nelson, MD PhD, Randy Woltjer MD PhD, Joseph F. Quinn MD, Jeffery Kaye MD, James B Leverenz MD, Debby Tsuang MD, MSc, Katelan Longfellow MD, Dora Yearout BS, Walter Kukull PhD, C. Dirk Keene MD, PhD, Thomas J. Montine MD, PhD, Cyrus P. Zabetian MD MS, John Q. Trojanowski MD PhD

2nd Place
ClinRes2Clinical Profile of Older Adults with Mild or No Cognitive Impairment Who Receive Prescriptions for Cholinesterase Inhibitors and/or Memantine: A descriptive study from the PACE/PACENET BHL Caregiver Resources, Education and Support (CREST) Program
Presenter: Romika Dhar, MD
Authors: Romika Dhar, MD; Amy Benson, MSEd; Joel E. Streim, MD; David W. Oslin, MD

* Due to the number of posters submitted, the categories for Clinical Research and Education & Community were combined.

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To view some of the full lectures from our retreat, click here.
* Please note: Some of the lectures are not available to view due to unpublished data being presented *

View more photos from our 2016 Sylvan M. Cohen Retreat Facebook album here.

Joseph A. Pignolo Award in Aging Research 2015: “REST and Stress Resistance in Aging and Alzheimer’s Research”

On Tuesday, March 1, 2016, the Institute on Aging presented their annual Joseph A. Pignolo Award in Aging Research. This year’s awardee was Bruce A. Yankner, MD, PhD, professor of Genetics and Neurology and Co-director of the Glenn Center for the Biology of Aging at Harvard Medical School, for his 2014 publication in Nature on “REST and Stress Resistance in Aging and Alzheimer’s Research.

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John Q. Trojanowski, MD, PhD (IOA Director), Bruce A. Yankner, MD, PhD (2016 Pignolo Awardee), and Robert J. Pignolo, MD, PhD (founder of the Pignolo Award in Aging Research).

This paper analyzes the gene expression changes that occur in the aging brain and shows the coherent pattern of changes in genes that turn on or off in the neurons of the brain as it ages. The greatest impact was seen in the REST (RE1 neuron-silencing transcription factor) gene. It was previously thought that this gene only functioned in fetal brain development—keeping neural genes at bay until the brain had a chance to build its underlying architecture—however, Dr. Yankner and his team found that it is also expressed in the adult human brain and is dramatically up-regulated in neurons as the brain ages. The significance of this in neurodegenerative research is that they discovered that in the brains of individuals with Alzheimer’s disease, the protein is actually much less up-regulated, or completely absent.

Using both mouse models and culture dishes in a laboratory, they found that regular stressors encountered by an aging brain such as oxidative stress—a disturbance in the balance between the production of reactive oxygen species and antioxidant defenses—and amyloid stress associated with AD had a significant impact on sustaining the REST gene.

“This was a galvanizing observation for us,” explained Dr. Yankner. “It suggested that some people can resist the onslaught of Alzheimer’s because they’re able to up-regulate this intrinsic defense mechanism [REST]. So, a very important question is why some people can do it and some people can’t…”

Dr. Yankner assumes there is a potential genetic underpinning, but also believes that environmental factors contribute as well.

In terms of future research, and based on their current findings, Dr. Yankner and his lab are interested in understanding exactly how REST accomplishes its different functions and manages to maintain neurons in a functional state for so many years. To do this, they are characterizing all of the genes and protein partners that interact with REST and are looking at them as potential therapeutic targets that may be used to delay the onset of Alzheimer’s disease.

View more photos from the 2016 Joseph A. Pignolo Award in Aging Research.

*This study was funded by the National Institute on Aging, the National Institutes of Health Common Fund (NCF), and the Paul F. Glenn Foundation for Medical Research.

 The main focuses of Dr. Yankner’s lab are to understand 1) the molecular biology of the aging brain and how that intersects with pathological aging in diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and Frontotemporal degeneration (FTD) and 2) using humans as a model system by understanding how they age in the brain, from changes in genes, DNA, and proteins, and modeling this in cells in culture and genetically engineered model systems including C. elegans (Caenorhabditis elegans) nematode worms.

The Joseph A. Pignolo, Sr. Award in Aging Research is given out as part of the Institute on Aging (IOA) Visiting Scholars series to annually recognize an outstanding contribution to the field of biogerontology. It was created by geriatrician and gerontologist Robert J. Pignolo, M.D., Ph.D. in honor of his father.

Innovative Approaches to Research on Alzheimer’s Disease Prevention: Designing and Implementing Large-Scale Studies

Last week, the IOA welcomed Dr. Fran Grodstein, ScD, Epidemiologist at Brigham and Women’s Hospital and Professor of Medicine at Harvard Medical School, to discuss “Innovative Approaches to Research on Alzheimer’s Disease Prevention: Designing and Implementing Large-Scale Studies.”

Dr. Grodstein’s primary research focus is on healthy aging in women. Her team has recently been exploring the topic of research methods and how researchers can conduct much larger studies than in the past. Using simpler methods such as telephone screenings and computerized testing they suspect that participation will be much more convenient and appealing–resulting in larger sample sizes.

In the past, much of Dr. Grodstein’s research has been on how people can modify lifestyle to stay healthy. She has looked at specific ways to maintain memory, avoid major diseases, live longer, and avoid mental health issues such as depression. Some findings show that the following factors play a major role in living longer, healthier lives:

  • Diet: An increase in fruits and vegetables, with berries being particularly important for brain health
  • Exercise: Simply walking to stay active seems to be adequate
  • Moderate Alcohol Intake: One serving of any alcohol per day seems to work just as well as red wine
  • Maintaining a healthy weight

Learn more about Dr. Grodstein’s research here:

For Dr. Grodstein’s full lecture, click here.