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. Dolatshahi[/caption]
Mahsa Dolatshahi, M.D., M.P.H.
Post-doctoral research fellow
Mallinckrodt Institute of Radiology (MIR)
Washington University School of Medicine
St. Louis
MedicalResearch.com: What is the background for this study?
Response: Obesity at midlife is recognized as a risk factor for developing Alzheimer disease decades afterwards. However, body mass index on its own does not adequately represent the risks associated with obesity.
In this study, we went beyond BMI and considered anatomical distribution of body fat, including the metabolically active visceral fat in the belly, and showed its association with Alzheimer pathology in the form of amyloid proteins. In addition, visceral fat along with obesity and insulin resistance were associated with thinning of brain cortex, as early as midlife.
Dr. Belloy[/caption]
Michael E. Belloy, PhD
Department of Neurology and Neurological Sciences
Stanford University, Stanford, California
MedicalResearch.com: What is the background for this study?
Response: Apolipoprotein E (APOE)*2 and APOE*4 are, respectively, the strongest protective and risk-increasing, genetic variants for late-onset Alzheimer disease. As such, one’s APOE genotype is highly relevant towards clinical trial design and Alzheimer’s disease research. However, most insights so far are focused on the associations of these APOE genotypes with Alzheimer’s disease risk in non-Hispanic white individuals.
One important aspect of our work is that we really increased sample sizes for non-Hispanic Black, Hispanic, and East Asian individuals, so that we now have better understanding of the associations of APOE genotypes with Alzheimer’s disease risk in these groups. In complement, we also did the largest investigation to date on the role of ancestry on the associations of APOE genotypes with Alzheimer’s disease risk. The scale of our study was thus a critical factor in generating novel insights.
Julia Cave Arbanas[/caption]
Julia Cave Arbanas
Project Manager and
Dr. Dunietz[/caption]
Galit Levi Dunietz MPH, PhD
Assistant Professor
Dr. Braley[/caption]
Dr. Willette[/caption]
Auriel Willette, PhD
Assistant Professor
Food Science and Human Nutrition
Iowa State University
MedicalResearch.com: What is the background for this study?
Response: To date, pharmacology therapies done to slow down or halt Alzheimer's disease have been inconclusive. Lifestyle interventions like changes in diet and activity are also mixed but do show some promise. Dietary clinical trials or self-reported diet have tended to focus on groups of foods such as the Mediterranean or MIND diet. To build from this excellent work, we were curious if we could pinpoint specific foods that were correlated with changes in fluid intelligence over time. Fluid intelligence represents our ability to creatively use existing knowledge, working memory, and other components of "thinking flexibly."
Further, we tested if these patterns of association differed based on genetic risk. In this case, genetic risk was defined as having a family history of Alzheimer's disease or having 1-2 "bad" copies of the Apolipoprotein E (APOE) gene, which is the strongest genetic risk factor for Alzheimer's disease.
Dr. Jensen[/caption]
Majken K. Jensen, Ph.D.
Adjunct Professor of Nutrition
Harvard T.H. Chan School of Public Health &
Professor in the Department of Public Health
University of Copenhagen, Copenhagen, Denmark
MedicalResearch.com: What is the background for this study?
Response: Alzheimer’s disease and other dementias are highly prevalent conditions. According to the Alzheimer’s Association, 50 million people are currently living with Alzheimer’s disease or other dementias worldwide. Lower apolipoprotein E in plasma is a risk factor for dementia, but the underlying biological mechanisms are not fully understood. Thus, we investigated the role of apolipoprotein E overall and in lipoproteins with distinct metabolic functions in relation to cognitive function and dementia risk..
