The Science of Aging: An IOA Newsletter, Fall 2023 Edition | DIGITAL VERSION
A LOOK INSIDE:
- TRIM11: A promising target for developing Alzheimer's Disease treatment
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Detailed 3D Mapping of AD Pathology Using Ex Vivo Imaging of the MTL
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FDA Fully Approves Lecanemab for Treatment of Alzheimer’s Disease
TRIM11: A promising target for developing Alzheimer’s Disease treatment
Penn Medicine researchers have identified TRIM11 – a tau-regulating protein – as a promising target for developing Alzheimer’s disease (AD) treatment.
According to the Penn Medicine News Release highlighting the study, which is led by senior author Xiaolu Yang, PhD, a professor of Cancer Biology at Penn Medicine, TRIM11 was found to suppress deterioration in small animal models of neurodegenerative diseases similar to AD, while improving cognitive and motor abilities. It also appears to play a key role in removing the protein tangles that cause neurodegenerative diseases like AD.
After examining postmortem brain tissue of 23 individuals with AD and 14 healthy controls from Penn’s Center for Neurodegenerative Disease Research (CNDR) brain bank and finding substantially reduced levels of TRIM11 in AD brains vs the healthy controls, Yang and his team used adeno-associated viral vector (AAV) to deliver the TRIM11 gene into the brains of multiple mouse models. Findings showed tht mice with tau pathologies receiving the TRIM11 gene experienced a decrease in the development and accumulation of neurofibrilary tangles (NFTs), and had much improved cognitive and motor abilities.
While other studies have previously reported various connections between TRIM genes and tau or other proteins associated with neurodegeneration -- such as TRIM28 and TRIM21 -- this study reveals a direct role for TRIM11 in suppressing tau aggregation and the underlying mechanism.
“Most organisms have protein quality control systems that remove defective proteins, and prevent the mis-folding and accumulation of tangles—like the ones we see with tau proteins in the brain of those with taupathies— but until now we didn’t know how this works in humans, or why it malfunctions in some individuals and not others,” explained Dr. Yang in the News Release.
“For the first time, we have identified the gene that oversees tau function, and have a promising target for developing treatments to prevent and slow the progression of Alzheimer’s disease and other related disorders,” he said.
This study was published in Science.
Detailed 3D Mapping of AD Pathology Using Ex Vivo Imaging of the MTL
One of the challenges of Alzheimer's Disease is the presence of co-pathologies; this means patients with AD tend to have other neurodegenerative pathologies present in their brains in addition to tau. To address this, researchers at Penn, in collaboration with researchers at University of Castilla-La Mancha, Spain are working to improve imaging-based biomarkers for AD by better understanding the spread of tau and its specific effects on neurodegeneration using postmortem, or ex vivo, MRI and histological imaging. Read more here.
Penn Medicine’s Li-San Wang, PhD, the Peter C. Nowell M.D. Professor of Pathology and Laboratory Medicine, is set to lead the Asian Cohort for Alzheimer’s Disease (ACAD) study, a project at Penn Medicine and 15 other academic research centers across the U.S. and Canada. The study is funded by a $40.5 million grant from the National Institute on Aging (NIA).
ACAD represents the first major Alzheimer’s disease genetics cohort for Asian Americans and Asian Canadians, which are two populations currently underrepresented in Alzheimer’s disease (AD) research. “This is a very ambitious project because we need to gather a critical mass of data on lifestyle and genetic risk factors to have enough statistical power to understand causes of the disease and strategies for treatment that may be specific to these Asian populations in the U.S. and Canada,” said Dr. Wang in the Penn Medicine News Release announcing the grant.
Researchers will analyze genetic data from cohort samples to identify risk variants in both U.S. and Canadian Asian populations, compared to other populations and to those living in Asia. They hope to use this information to help develop blood biomarker benchmarks and a polygenic risk score model to measure the risk for AD specifically among Asian Americans and Asian Canadians. Additionally, they will look at non-genetic biomarkers in combination with lifestyle and clinical information for clues suggesting other contributing factors to AD.
“A major priority of this project is to help the community – we’re not just going in and taking samples. The response during the pilot phase was incredible excitement to participate, which reinforced why we’re doing this and the need for health equity in Alzheimer’s disease research,” said Dr. Wang.
Dr. Wang also serves as the co-lead of the Data Management and Statistical Core at the Penn Alzheimer’s Disease Research Center and is an IOA Member.
FDA Fully Approves Lecanemab for Treatment of Alzheimer’s Disease
The U.S. Food and Drug Administration converted Leqembi (lecanemab-irmb), the first drug indicated to treat adult patients with Alzheimer’s by slowing the disease, to traditional approval following a determination that a confirmatory trial verified clinical benefit. Read more here.
Introducing the New IOA Members Research Database
The IOA is pleased to announce the launch of the IOA Members Database. This database will serve as a resource for those interested in aging and neurodegenerative disease-related research at Penn. The goal is to foster potential collaborative opportunities between IOA Members and those with similar research interests not only at Penn but at institutions nationwide.
“We are so excited to launch the IOA Members Research Database. We often get requests from faculty who are looking for collaborators in a specific area and now we have a resource to easily identify them,” said Kathy Jedrziewski, PhD, IOA Deputy Director.
View the IOA Members Research Database here.
IOA Strategic Plan for ADRD 2023-2028
In May, The Institute on Aging launched the IOA Strategic Plan for Alzheimer’s Disease and Related Dementias (ADRD). This plan aims to promote, facilitate and enhance the use of multidisciplinary research approaches to achieve groundbreaking discoveries that can advance the field. Read more here.
Meet our 2023/2024 PennPREP Scholar
Annie Abioye has been selected as the 2023-2024 IOA-supported PennPREP Scholar. She is a recent graduate from Indiana University where she earned a B.S. in neuroscience and worked in a neuroimaging lab. As a PennPREP scholar, Annie will be engaging in cognitive research with the Kable Lab, which seeks to understand how people make decisions, and to trace out the psychological and neural mechanisms of choice.
“I am hoping to gain more experience in a new area of neuroscience research and refine my skills in scientific communication,” she said. “In the future, I am aiming for acceptance into a Medical Scientist Training Program to become a physician-scientist.”
- David Wolk, MD, IOA Co-director and leader of the IOA’s Division of Clinical and Translational Neurodegenerative Disease Research, co-authored a review in Annals of Neurology arguing the clinical importance of limbic-predominant age-related TDP-43 encephalopathy (LATE). The review argues that LATE is a common mimic of Alzheimer’s Disease based on shared signs and symptoms, but that there are potential diagnostic tools that help with diagnosis. They also discuss potential treatment implications for LATE that may be beneficial for physicians, patients, and families. Dr. Wolk also co-chaired a National Institute on Aging (NIA) workshop on the topic last Spring.
- Eddie Lee, MD, PhD, IOA Co-director and leader of the IOA’s Division of Basic Neurodegenerative Disease Research, helped organize the AAIC Neuroscience Next events hosted at the University of Pennsylvania in April. The conference showcased the work of students, postdoctoral researchers and early career research professionals in cognitive, computational, behavioral, and other areas of neuroscience research. Dr. Lee also received the Alzheimer’s Association Excellence in Neuroscience Mentoring Award for his dedication to educating the next generation of neuroscientists and physician-scientists.
- Anne R. Cappola, MD, ScM, a Professor of Medicine in the Division of Endocrinology, Diabetes and Metabolism and division co-leader of the IOA’s Division of Geroscience, Gerontology, and Geriatrics, recently chaired the Scientific Statement from the Endocrine Society, “Hormones and Aging: An Endocrine Society Scientific Statement”, published in the Journal of Clinical Endocrinology and Metabolism. “The goal of this statement is to inform future research that refines prevention and treatment strategies in age-associated endocrine conditions,” explained Dr. Cappola.
- “Racial and Ethnic Disparities in Access to and Enrollment in High-quality Medicare Advantage Plans,” co-authored by Norma B. Coe, PhD, Co-Director of Penn’s Population Aging Research Center (PARC) and leader of the IOA’s Division of Epidemiology, Social Science, and Policy, was selected as Health Services Research’s 2023 John M. Eisenberg Article of the Year.
- Work by Brad Johnson, MD, PhD, Professor of Pathology and Laboratory Medicine and co-leader of the IOA’s Division of Geroscience, Gerontology, and Geriatrics, and his team was recently published in Cellular and Molecular Gastroenterology and Hepatology. The work highlighted in the paper, Patient-Induced Pluripotent Stem Cell-Derived Hepatostellate Organoids Establish a Basis for Liver Pathologies in Telomeropathies, contributes to the understanding of age-related liver diseases, and to potential novel approaches to their treatment, explained Dr. Johnson.