Alzheimer's - Dementia, Author Interviews, Case Western / 25.12.2025
Case Western Scientists Reverse Advanced Alzheimer’s Pathology in Mice
MedicalResearch.com Interview with:
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Dr. Pieper[/caption]
Andrew A. Pieper M.D., Ph.D.
Professor, Department of Psychiatry, School of Medicine
Professor, Department of Neurosciences
Professor, Department of Pathology
Investigator, University Hospitals Harrington Discovery Institute, Harrington Discovery Institute
Associate Director, Medical Scientist Training Program, School of Medicine
Case Western Reserve University, University Hospitals Cleveland Medical Center, and
at the Louis Stokes Cleveland VA Medical Center
MedicalResearch.com: What is the background for this study?
Response: NAD+, a central cellular energy and signaling molecule, declines with age throughout the body, including the brain. When NAD+ falls below necessary levels, cells lose their ability to carry out essential maintenance and survival functions. We found that the NAD+ decline is more severe in brains from people with Alzheimer’s disease (AD) and in mouse models of AD, whereas brains of people with AD pathology but preserved cognition show gene-expression patterns consistent with maintained NAD+ homeostasis.
Dr. Pieper[/caption]
Andrew A. Pieper M.D., Ph.D.
Professor, Department of Psychiatry, School of Medicine
Professor, Department of Neurosciences
Professor, Department of Pathology
Investigator, University Hospitals Harrington Discovery Institute, Harrington Discovery Institute
Associate Director, Medical Scientist Training Program, School of Medicine
Case Western Reserve University, University Hospitals Cleveland Medical Center, and
at the Louis Stokes Cleveland VA Medical Center
MedicalResearch.com: What is the background for this study?
Response: NAD+, a central cellular energy and signaling molecule, declines with age throughout the body, including the brain. When NAD+ falls below necessary levels, cells lose their ability to carry out essential maintenance and survival functions. We found that the NAD+ decline is more severe in brains from people with Alzheimer’s disease (AD) and in mouse models of AD, whereas brains of people with AD pathology but preserved cognition show gene-expression patterns consistent with maintained NAD+ homeostasis.
Dr. Zeynep Gümüş[/caption]
Zeynep H. Gümüş, PhD
Associate Professor
Icahn School of Medicine at Mount Sinai
MedicalResearch.com: What is the background for this study?
Response: The germline genome of each individual person has a unique combination of millions of genetic variants that influence virtually all biological processes throughout life, including cancer evolution. In this study, we have investigated the impact of germline variants – genetic defects one is born with – on gene expression and protein abundance in tumors across cancer types.
MedicalResearch.com: Would you describe the technique of precision peptidomics?
Response: We have leveraged a cohort of 1,064 patients with multiple cancer types to explore the impact of germline variations on cancer-relevant genes through multiple-omics layers: from DNA to RNA, protein abundance and post-translational modifications. To assess the effects of coding variants and their association with cognate proteins, we used precision peptidomics, which is the quantification of peptides carrying genetic variants from individual patients. Through this approach, we mapped 337,469 protein coding germline variants onto patient peptides, revealing their potential impact on protein modifications, protein stability, allele-specific expression, and protein structure by leveraging the relevant protein databases.
Dr. Li Gan[/caption]
Dr. Li Gan PhD
Burton P. and Judith B. Resnick Distinguished Professor in Neurodegenerative Diseases
Brain and Mind Research Institute
Weill Cornell Medical College
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Dr. Traverso[/caption]
Giovanni Traverso MD PhD
Karl Van Tassel (1925) Career Development Professor
Department of Mechanical Engineering
Koch Institute of Integrative Cancer Research
Division of Gastroenterology
Brigham and Women’s Hospital
Harvard Medical School, Boston, MA, USA
MedicalResearch.com: What is the background for this study?
Response: I think its always important to acknowledge that this is a big team effort. We have the teams from MIT, Celero Systems, West Virgnia University (WVU) and Brigham and Women’s Hospital (BWH) all working together on this. For this study, Celero prototyped the devices that we tested in pre-clinical (Swine) models and in a first-in-human study with the team at WVU.
Our lab focuses on the development of ingestible devices for drug delivery and sensing and these have informed the development of these efforts as you can see.