Why Women May Be More Susceptible to Alzheimer’s Disease
CLEVELAND—Case Western Reserve University researchers associated with the CADRC Translational Therapeutics Core have identified a mechanism in brain tissue that may explain why women are more vulnerable to Alzheimer’s disease—a finding that they say could help lead to new medicines to treat AD.
Specifically, the researchers found that the female brain shows higher expression of a certain enzyme compared to males, resulting in greater accumulation of a protein called tau. The tau protein is responsible for the formation of toxic protein clumps inside brain nerve cells of Alzheimer’s disease patients.
The enzyme, known as ubiquitin-specific peptidase 11 (USP11), is X-linked, meaning it is found in genes on the X chromosome, one of the two sex chromosomes in each cell.
“We are particularly excited about this finding because it provides a basis for the development of new neuroprotective medicines,” said David Kang, the Howard T. Karsner Professor in Pathology at the Case Western Reserve School of Medicine and co-senior author of a study published today in the journal Cell. “This study also sets a framework for identifying other X-linked factors that could confer increased susceptibility to tauopathy in women.”
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Cleveland Alzheimer’s Disease Research Center
The Cleveland Alzheimer’s Disease Research Center (CADRC) is a research program led by Case Western Reserve University (CWRU), Cleveland Clinic (CCF), University Hospitals (UH), the Louis Stokes VA, and MetroHealth. The CADRC is a center without walls as it is not a specific building or place. Instead, the CADRC includes top scientists and doctors from the Cleveland area, working together to learn more about Alzheimer’s disease and Related Dementias (ADRD). The goal of the CADRC is to help find treatments to improve the lives of patients and their families. The CADRC enrolls people with brain disorders like Alzheimer’s disease, Lewy Body Dementia, or Atypical dementia. We also enroll people without memory problems. Our CADRC clinical sites (CCF and UH) run memory tests, lab tests, and other brain tests such as MRI scans. The CADRC raises awareness of ADRD and involves people in the community.
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September 21, 2022, was World Alzheimer’s Day: A Time to Raise Awareness About AD
The Daily (CWRU Digital Newsletter) sat down with Dr. Jonathan Haines, an internationally recognized researcher and educator, and CADRC Data Management and Statistics Core Leader, to learn more about Alzheimer’s disease, which has been a major focus of his for decades.
“There’s a general misconception that having memory problems and having Alzheimer’s disease is a natural aging process, and it’s not,” Haines explained. “There are quite a few people who are in their 90s who are just as sharp as they were when they were in their 20s.”
Dr. Haines lists five things everyone should know about Alzheimer’s disease.
Read the full story in The Daily here
Professor Andrew A. Pieper is Recipient of the Barchas Chair, Endowed Professorship
Dr. Rebecca Barchas established at Case Western Reserve a $3.5M endowed professorship in translational psychiatry, with resources to support that faculty member’s research.
The medical school celebrated the inaugural recipient of the Barchas Chair, Case Western Reserve University Psychiatry Professor Andrew A. Pieper, an accomplished psychiatrist and neuroscientist dedicated to both treating patients in his outpatient clinic and discovering treatments in his laboratory that alleviate or even cure the damage of brain trauma and neurodegenerative diseases.
Translational psychiatry, an area of passion for Barchas since childhood, involves the process of first making basic science discoveries in laboratory models and then advancing those findings to the development of new medicines for patients.
“These types of early stage, high risk, high reward strategies are not typically supported by traditional National Institutes of Health-style funding, and would be impossible without her philanthropic generosity.” A. Pieper
For Pieper, who is also director of the Center for Brain Health Medicines at University Hospitals Harrington Discovery Institute and director of the Translational Therapeutics Core of the Cleveland Alzheimer’s Disease Research Center (CADRC), Barchas’ gift will provide resources for initial exploration of the kinds of breakthrough ideas federal agencies and other large organizations are hesitant to back without significant evidence of their promise.
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Case Western Reserve University Researcher of the CADRC Helps to Expand Alzheimer’s Disease Research with Cleveland’s African American Communities
CLEVELAND—Case Western Reserve University (CWRU) researchers focused on the genetics of Alzheimer’s Disease (AD) in individuals with African ancestry have secured $46M in funding through the National Institutes of Health’s (NIH) National Institute on Aging to expand community outreach.
Data Management and Statistics Core Leader
This is part of a nationwide effort to better understand a disease that presents differently—and at different rates—in communities that historically have not been included in large-scale genetic research.
“This enhances research that is foundational to developing prevention strategies, earlier diagnostic tests and treatments for a condition that has no boundaries,” said Jonathan L. Haines, PhD, the CADRC Data Management and Statistics Core Leader and lead investigator and chair of the Department of Population and Quantitative Health Sciences, and the Mary W. Sheldon, MD, Professor of Genomic Sciences.
“We are already engaged in the Cleveland area with African American individuals and families who are important partners in this work,” he said. “We are committed to our local community, and this increased capacity ensures that large-scale research benefits everyone.”
The full consortium, which includes three investigators at CWRU, will also engage with Hispanic and Afro-Hispanic communities nationally. Additionally, the consortium will collaborate with AD genetic researchers across nine African countries. Altogether, these researchers will collect, match, and analyze data at the scale required to uncover genetic variants associated with AD.
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Needs Survey
Researchers from the Cleveland Alzheimer’s Disease Research Center (CADRC) welcome members of all communities to check out our website and provide their input on how the CADRC can best meet the needs of individuals and families. We also want to hear from groups/entities interested in advancing care and research on Alzheimer’s Disease and related dementias. Please complete our CADRC needs survey to help us do a better job in serving our community and planning for programing that you feel would be most helpful: https://redcap.case.edu/surveys/?s=P3M38AFHF4AWHPDM
CADRC Investigator News
Funding Announcements
New 5-Year National Institute of Aging (NIA) Research Grant Awarded to Dr. Jagan Pillai to Evaluate Immune Cell Activation and Blood Brain Barrier Changes at Different Stages of Alzheimer’s Disease
Dr. Jagan Pillai, Cleveland Clinic Lou Ruvo Center for Brain Health and CWRU and falls under the umbrella of research conducted by the Cleveland Alzheimer’s Disease Research Center (CADRC). His research study just started, September 2022, and will evaluate immune cell activation and blood brain barrier(BBB) changes at different stage of Alzheimer’s disease. This will help develop therapeutic targeting of specific immune and BBB changes at the most effective clinical stage of Alzheimer’s disease to make a useful clinical impact in overcoming cognitive decline.
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U.S. National Institute of Health (NIH) Awards 5-Year Grant to Dr. Stephen Rao and Dr. Jay Alberts to Study the Impact of a Home Based, High Intensity Exercise Program for Those Who Have a Genetic Risk for Alzheimer’s Disease (AD)
Dr. Stephen Rao, PhD, who is a co-investigator in the CADRC Clinical Core and Dr. Jay Alberts, PhD, a kinesiologist with specialization in the field of motor control have been awarded a 5-year NIH research grant for a randomized controlled trial which aims to study the impact of a home based, high intensity exercise program in healthy older adults between the ages of 65 and 80 years, who have a genetic risk for Alzheimer’s disease (AD) but do not have any memory concerns. The CYCLE-AD trial will recruit healthy sedentary APOE e4 carriers and randomize them to one of two groups: 1) an Indoor Cycling (IC) group that participates in high-intensity interval training in their home using a commercially available Peloton® cycling system or 2) a Usual and Customary Care (UCC) group, in which participants engage in their habitual level of physical activity.
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National Institute on Aging Awards
$2 Million to Dr. Wenzhang Wang to Study
ApoE and Abeta Which is Believed to Be a Key Cause of Alzheimer’s Disease
July 1, 2022, CLEVELAND: The National Institute of Aging (NIA) has awarded a $2 million, 5-year research grant to Dr. Wenzhang Wang, who is a Cleveland Alzheimer’s Disease Research Center (CADRC) Research Education Component Mentee. Dr. Wang will study ApoE, an Alzheimer’s disease (AD) risk factor gene, and Abeta, a protein that is deposited on the brain, in the regulation of mitochondria and lysosome interactions in AD. The project will be conducted at Case Western Reserve University School of Medicine and falls under the umbrella of research conducted by the CADRC.
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