It is widely known that Alzheimer’s is a heterogeneous disease. Patients may present differently not only with varying ages of onset, but also with the type of clinical symptoms they may experience ranging from problems with memory or language, spatial difficulty, or problems with motor function. 

Renaud La Joie, PhD, Assistant Professor in Department of Neurology’s Memory and Aging Center at the University of California San Francisco recently presented at the University of Pennsylvania as part of the Institute on Aging’s Visiting Scholars Series to share how he and his team are working to better understand how these clinical symptoms relate to what is happening in the brains of Alzheimer’s disease patients using biomarkers and imaging. 

“What’s really unique about Alzheimer’s disease is that its characterized by the presence of two different types of abnormal proteins in the brain – amyloid plaques and tau pathology with many neurofibrillary tangles and other types of lesions,” said Dr. La Joie. “In our work, we are trying to bridge the heterogeneity we see in patients clinically to the proteins in the brain and what we [found] is, most of the variability across patients in terms of what type of symptoms they have and how old they are when they develop symptoms is related to the regional distribution and amount of tau pathology, not amyloid.”

Now, they are trying to understand when Alzheimer’s pathology happens, why some patients are more prone to getting pathology in certain brain areas versus the others. 

“It is going to take a lot of different multidisciplinary approaches to tackle this question, including genetics and basic science to understand different properties of different brain regions and why some regions are more vulnerable in some patients compared to others,” said Dr. La Joie. 

From the patient perspective, their hope is that this information will help the field better understand what kind of biomarkers can be informative at what disease stage. Right now, available biomarkers include imaging, measures from CSF, blood biomarkers, etc. but these measures are not all interchangeable and provide different types of information. 

“I think our research shows that tau PET, for example, can be very helpful to confirm the presence of Alzheimer’s pathology and also predict what may happen to the patient in the near future,” said Dr. La Joie. “The one thing that were really missing right now are biomarkers as a way of detecting other types of disease in the brain because we know that unfortunately, most patients with Alzheimer’s also have other types of pathologies in the brain and we think that all these pathologies together contribute to the clinical symptoms. So, right now we can only identify the presence of amyloid and tau, and everything else is kind of out of reach for us, but I’m really excited by some recent developments of biomarkers measuring other proteins like alpha synuclein and maybe in the future TDP-43.”

• Genetic Variant, TREM2, Associated with Atypical Alzheimer’s Disease
  
• IOA Divisions
  
• IOA Retreat 2022: Fluid Biomarkers in AD
  
• Meet our IOA PennPREP Scholar
  
• IOA Members Program

Genetic Variant, TREM2, Associated with Atypical Alzheimer’s Disease

A University of Pennsylvania-led research study suggests that the rare genetic variant,TREM2, increases one’s risk of Alzheimer’s disease (AD) but also causes atypical symptoms. This finding could have a significant impact on how AD is diagnosed. 

“We were able to demonstrate, with the largest brain autopsy study of cases with this genetic risk variant to date, that TREM2 variants are associated with these atypical Alzheimer’s disease symptoms,” said Edward Lee, MD, PhD, Co-director of the Institute on Aging (IOA) and Co-associate director of the University of Pennsylvania’s Alzheimer’s Disease Research Center (ADRC).

The study used 54 cases with 14 different types of TREM2 variants identified from the Center for Neurodegenerative Disease Research (CNDR) brain bank at Penn. Researchers gathered genetic, demographic, and diagnostic information to better understand how TREM2 works in patients with AD. When patients had the TREM2 variant, the team found that they often had a faster cognitive decline.  

The team also compared the neuropathology, or brain tissue, between those with and without TREM2. These findings confirmed that even with atypical symptoms, many patients with the TREM2 variant do have AD.

“We did not see any difference in amyloid or the amount of tau,” said Boram Kim, a postdoctoral fellow in the Translational Neuropathology Research Laboratory at the Perelman School of Medicine, University of Pennsylvania and lead author of the study. “But the spreading patterns of tau varied.”

“Not only will this potentially help guide a personalized approach to dementia diagnosis, this study provides useful insights into the basic processes that lead to dementia,” said Dr. Lee.

This research study was published in Acta Neuropathologica.

Introducing IOA Divisons

With the recent leadership transition, the IOA has the opportunity to refresh its organizational structure. In alignment with its mission to improve the health of older adults by increasing the quality and quantity of clinical and basic research as well as educational programs focusing on normal aging and aging-related diseases across the entire Penn campus, the IOA will focus its efforts in four main areas, or IOA Divisions.

Each division is led by members of the Penn faculty with expertise in their designated division who will serve liaisons for potential collaboration within the organization and help shape future IOA initiatives. 

• Division of Basic Neurodegenerative Disease Research
• Division of Clinical and Translational Neurodegenerative Disease Research
• Division of Geroscience, Gerontology, and Geriatrics
• Division of Epidemiology, Social Science, and Policy

IOA Retreat 2022: Fluid Biomarkers in Alzheimer’s Disease Research

This year’s IOA Sylvan M. Cohen Annual Retreat focused on fluid biomarkers, the next wave of diagnostic tools in Alzheimer’s disease (AD).

“Biomarkers are an important part of dementia research. They help researchers detect early brain changes, better understand how risk factors are involved, identify participants who meet particular requirements for clinical trials and studies, and track participants’ responses to a test drug or other intervention, such as physical exercise.” – nia.nih.gov

Topics covered included an update on biofluid-based biomakers for amyloid and neurodegeneration by Henrik Zetterberg, MD, PhD, professor at the University of Gothenburg, Sweden, and University College London, and plasma tau biomarkers in acute and chronic neurological diseases by Thomas Karikari, PhD, assistant professor at the University of Pittsburgh.

Several Penn presenters also shared their research in the field. This year’s lineup included Katheryn A.Q. Cousins, PhD, Tom Tropea, DO, MPH, MTR, Les Shaw, PhD, Jina Ko, PhD, and Ramon Diaz-Arrastia, MD, PhD.

“My hope is that we develop biomarkers for non-AD pathologies; we desperately need things for TDP-43, alpha-synuclein, other proteinopathies,” said Eddie Lee, MD, PhD, neuropathologist and co-director of the IOA, when asked about thoughts on the future of biomarkers in AD research.

Meet our IOA PennPREP Scholar

The University of Pennsylvania Post-Baccalaureate Research Education Program (PennPREP) offers a one-to-two-year research experience for students, who have completed their bachelor’s degree, are interested in pursuing a doctoral degree in the biomedical sciences, and would benefit from protected time to develop additional skills research. The program provides a full time research experience in a biomedical science discipline, along with preparation for applying to and succeeding in graduate school. 

PennPREP is one of many PREP initiatives across the country meant to increase STEM diversity, specifically targeting Black/African-Americans, Hispanic/Latino/Chicano Americans, Native Americans and Alaskan Natives, and Pacific Islanders.

As part of the IOA’s recent restructure, one of our new endeavours is to support a student in the program as an IOA PennPREP Scholar. Meet our first IOA PennPREP Scholar, Lauryn Brooks.

Working in the lab of Dr. Foteini Mourkioti in the McKay Department of Orthopedic Research, Brooks is currently studying the Mechanosensing Ion Channel, Piezo 1, and its role in skeletal muscle function. Piezo 1 regulates the influx of calcium ions into the cell as calcium is essential to muscle contractions. Using mouse models to knock out Piezo 1 in muscle fiber, Brooks is studying how the lack of Piezo 1 affects muscle fiber physiology and function, and how this may be affected by aging. 

“I aspire to become a physician-scientist and continue to work in the field of bioengineering,” said Brooks. “PREP has given me the opportunity to conduct research, shadow physicians, and take graduate-level courses which will bolster my future graduate school applications.”

Lauryn Brooks graduated with a B.S. in Biochemistry from Hampton University in May 2022 and has held many internships in a wide range of disciplines gaining experience from the National Institutes of Health, the Broad Institute of Harvard and MIT, Michigan State, and the Seattle Structural Genomics Center for Infectious Disease.

IOA Members Program

Are you a Penn faculty member (or know someone who is!) interested in aging and/or neurodegenerative disease research?

Join our new IOA Members program!

Benefits of IOA Membership:

• Potential funding of IOA Post-doctoral fellows
• Potential funding of IOA PennPREP Scholar(s)
• Identification of potential invited speakers to present at the IOA Seminar Series
• Priority for scheduled meetings with IOA Seminar Series speakers
• Trainees eligible to present at IOA-sponsored trainee seminars
• Trainees eligible to attend IOA-sponsored career development activities
• Participate in shaping the future of aging research at Penn

Each IOA Member must identify with at least one of the four new IOA Divisions.

“Biomarkers are an important part of dementia research. They help researchers detect early brain changes, better understand how risk factors are involved, identify participants who meet particular requirements for clinical trials and studies, and track participants’ responses to a test drug or other intervention, such as physical exercise.” – nia.nih.gov

Topics covered included an update on biofluid-based biomakers for amyloid and neurodegeneration by Henrik Zetterberg, MD, PhD, professor at the University of Gothenburg, Sweden, and University College London, and plasma tau biomarkers in acute and chronic neurological diseases by Thomas Karikari, PhD, assistant professor at the University of Pittsburgh.

Several Penn presenters also shared their research in the field. This year’s lineup included Katheryn A.Q. Cousins, PhD, Tom Tropea, DO, MPH, MTR, Les Shaw, PhD, Jina Ko, PhD, and Ramon Diaz-Arrastia, MD, PhD. 

“My hope is that we develop biomarkers for non-AD pathologies.” said Eddie Lee, MD, PhD, neuropathologist and co-director of the IOA, when asked about his thoughts on the future of biomarkers in AD research. “We desperately need things for TDP-43, alpha-synuclein, other proteinopathies.”

2022 Poster Winners

Introducing IOA Divisions

With the recent leadership transition, the IOA has the opportunity to refresh its organizational structure. In alignment with its mission to improve the health of older adults by increasing the quality and quantity of clinical and basic research as well as educational programs focusing on normal aging and aging-related diseases across the entire Penn campus, the IOA will focus its efforts in four main areas, or IOA Divisions.

Each division is led by members of the Penn faculty with expertise in their designated division who will serve liaisons for potential collaboration within the organization and help shape future IOA initiatives. 

MEET OUR IOA DIVISIONS

Division of Basic Neurodegenerative Disease Research

This division focuses on basic, mechanistic research into the pathophysiology of neurodegenerative diseases including Alzheimer’s disease and related dementias (frontotemporal degeneration, dementia with Lewy bodies), movement disorders, and motor neuron diseases.  The key strengths and focus of this division have been in biochemistry, genetics, and pathology.

Division Leader: Edward B. Lee, MD, PhD

Edward (Eddie) B. Lee, MD, PhD is currently Associate Professor in the Department of Pathology and Laboratory Medicine, Co-Director of the Penn Institute on Aging, and Associate Director of the Penn Alzheimer’s Disease Research Center.  He is also a practicing neuropathologist in the illustrious Division of Neuropathology.

Dr. Lee’s research involves using of advanced molecular, biochemical and histologic techniques to analyze brain tissue in study the molecular pathways associated with neuropathologic inclusions in frontotemporal lobar degeneration, amyotrophic lateral sclerosis, Alzheimer’s disease, and Trauma-Related Neurodegeneration.  He is the leader of the neuropathology cores of the Penn ADRC, the Penn FTDC, the Penn U19 Center on alpha-synuclein strains in ADRD, and the multi-institutional, international CONNECT-TBI consortium.

“My goal is to bring together world-class scientists by promoting the cross fertilization of diverse ideas, fostering successful collaborations, and recruiting the most promising trainees and faculty to the University of Pennsylvania in order to discover the causes and cures of aging-related neurodegenerative diseases.”

– Eddie Lee, MD, PhD

Division of Clinical and Translational Neurodegenerative Disease Research

This division focuses on translational and clinical research on neurodegenerative diseases including Alzheimer’s disease and related dementias (frontotemporal degeneration, dementia with Lewy bodies), movement disorders, and motor neuron diseases.  The key strengths and focus of this division include biomarker development and validation (biofluid, neuroimaging, multimodal integration), studies on the structure and function of the aging brain (neuropsychology, clinical outcomes, neuroimaging), and the development of care models.  This division encourages an emphasis on translating basic research into clinical trials and practice.

Division Leader: David A. Wolk, MD

Dr. David Wolk is a Professor of Neurology in the Cognitive Neurology Division of the University of Pennsylvania Perelman School of Medicine. He is also the Director of the Penn Alzheimer’s Disease Research Center (Penn ADRC), Co-director of the Institute on Aging, and Co-director of the Penn Memory Center. 

Dr. Wolk’s research has focused on the cognitive neuroscience of memory decline associated with aging and Alzheimer’s Disease using techniques including behavioral testing, structural and functional MRI, and FDG and molecular PET imaging. Much of this work is also directed at examining biomarkers, including behavioral and neuroimaging, that differentiate healthy aging from the earliest transition to AD and their potential role in understanding disease mechanisms and incorporation into treatment trials.

“The IOA has played a key role in my and many other careers at Penn by providing a forum for exchange of ideas, opportunities to present data and meet outside investigators, and recruitment of collaborative faculty. I would like the IOA to continue to serve as a milieu and forum for supporting the broad study of aging at Penn and to integrate and leverage the various lenses in which aging and age-related diseases are studied to promote healthier and happier aging.”

– David A. Wolk, MD

Division of Geroscience, Gerontology, and Geriatrics

This division focuses on basic, translational, and clinical research on human aging including basic molecular alterations (telomere biology, epigenetics, metabolism) and clinical phenotypes (frailty, integrated care models, metabolism).

Division Leaders: F. Bradley (Brad) Johnson, MD, PhD, and Anne Cappola, MD, ScM

Brad Johnson, MD, PhD is a Professor of Pathology and Laboratory Medicine, and Assistant Director of the Immunology and HLA Laboratory at the Hospital of the University of Pennsylvania.

Dr. Johnson’s research focuses on the basic biology of human aging and cancer, with an emphasis on how they are influenced by telomere maintenance and dysfunction. Currently, his lab is investigating roles for telomeres in diseases of the intestine, lung and liver.  Their broad goals are to better understand and treat telomere-driven diseases in individuals with inherited genetic deficiencies in telomere maintenance as well as in the elderly.

“Penn has deep yet diverse strengths spanning studies into the fundamental causes of aging to investigations of the nature of the many diseases for which aging puts people at a dramatically elevated risk.  I hope to help continue the IOA’s past successes of fostering collaboration among investigators across this spectrum to enhance human wellbeing into old age.”

– Brad Johnson, MD, PhD

Anne Cappola, MD, ScM is a Professor of Medicine in the Division of Endocrinology, Diabetes, and Metabolism; Director of the Penn Medical Communication Research Institute (PMCRI). She is an Associate Editor for the Journal of the American Medical Association (JAMA) and a member of the External Advisory Committee for Clinician-Scientists Transdisciplinary Aging Research (ClinSTAR).

Dr. Cappola leads an NIH-funded program focusing on the hormonal alterations that occur with aging and the clinical impact of these changes. Current projects include studies defining cutoffs for thyroid dysfunction in older men and women; the role of thyroid hormone treatment in cardiovascular disease, hormonal treatments for the frailty syndrome; and metabolic changes in men and women who sustain a hip fracture.

“Geroscience weaves together the basic and clinical science in aging, working together to study the underpinnings of chronic disease, frailty, and resilience. The IOA is the home for investigators performing research across these areas.”

– Anne Cappola, MD, ScM

Division of Epidemiology, Social Science, and Policy

This division focuses on social, ethical, and legal scholarship in addition to population science and epidemiology as it relates to neurodegenerative diseases and aging.  These include research on understudied populations (global, underrepresented), the social impact of aging-related diseases, ethical and health economics considerations in aging and neurodegenerative disease and their interface with policy and legal frameworks.

Division Leader: Norma Coe, PhD

Norma B. Coe, PhD, is an Associate Professor of Medical Ethics & Health Policy at the Perelman School of Medicine at the University of Pennsylvania. She is an economist whose research focuses on identifying causal effects of policies that directly and indirectly impact health, human behavior, health care access, and health care utilization.

Dr. Coe is the Director of the Policy and Economics of Disability, Aging, and Long Term Care (PEDAL) lab and Co-Director of the Population Aging Research Center (PARC). In her research, Dr. Coe merges the rigor of economic thinking and empirical analysis with the practical health services skills of measurement and knowledge of the health policy context to answer pressing questions for policymakers and other stakeholders on how we can improve aging in America.

“I look forward to helping to make connections between the social scientists and the bench scientists studying aging. Bench science discoveries are pushing the social sciences forward, such as studying the socioeconomic gradient in epigenetic clocks to help identify the social factors that contribute to biologic measures of aging. And we are only touching the tip of the iceberg.”

– Norma B. Coe, PhD

IOA MEMBERS PROGRAM

The new IOA Members program is open to all Penn faculty with research interests in aging and/or neurodegenerative disease.  

Benefits of IOA Membership:

• Potential funding of IOA Post-doctoral fellows
• Potential funding of IOA PennPREP Scholar(s)
• Identification of potential invited speakers to present at the IOA Seminar Series
• Priority for scheduled meetings with IOA Seminar Series speakers
• Trainees eligible to present at IOA-sponsored trainee seminars
• Trainees eligible to attend IOA-sponsored career development activities
• Participate in shaping the future of aging research at Penn

Each IOA Member must identify with at least one of the four IOA Divisions.

Sign up for the IOA Members program and select your division(s) here.