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Brain Hypometabolism, Oxidative Stress, Maternal Transmission, and Risk of Late-Onset Alzheimer’s Disease

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Studies on Alzheimer's Disease

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Abstract

Alzheimer’s disease (AD) is an age-dependent neurodegenerative disorder associated with progressive loss of cognitive function. Positron emission tomography (PET) imaging with 2-[18F]fluoro-2-deoxy-d-glucose (FDG) as the tracer has long been used to measure resting-state cerebral metabolic rates of glucose, a proxy for neuronal activity. Several FDG-PET studies have shown that metabolic reductions occur decades before onset of AD symptoms, suggesting that metabolic deficits may be an upstream event in at least some late-onset AD cases. This review explores this possibility, initially by discussing the link between AD pathology and neurodegeneration, with a focus on the metabolic pathways involved in neuronal function and bioenergetics, and the relationship between glucose metabolism, oxidative stress, and AD. This will be followed by a summary of the FDG-PET method, ranging from physics to kinetic modeling, and PET findings in AD. We will then discuss recent findings of progressive FDG-PET hypometabolism in adult children of mothers, but not fathers, affected by late-onset AD. Given the connection between glucose metabolism and mitochondria and the fact that mitochondrial DNA is maternally inherited in humans, it will be argued that altered bioenergetics may be an upstream event in individuals with a maternal family history of AD. Biomarkers of AD have great potential for identifying AD endophenotypes in cognitively intact individuals at risk for AD, which may help direct investigation of potential susceptibility genes.

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Acknowledgments

This study was supported by NIH/NIA grants AG035137, AG032554 and AG13616, NIH/NCRR grant M01-RR0096, and the Alzheimer’s Association. The Authors are indebted to Prof. Alberto Pupi, University of Florence, Italy, for his many insightful comments.

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Authors and Affiliations

  1. Department of Psychiatry, Center for Brain Health, NYU School of Medicine, 145 East 32nd Street, 2nd floor, New York, NY, 10016, USA

    Lisa Mosconi Ph.D., John Murray M.S., Pauline McHugh M.D. & Mony de Leon D.Ed.

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  1. Lisa Mosconi Ph.D.
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  2. John Murray M.S.
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  3. Pauline McHugh M.D.
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  4. Mony de Leon D.Ed.
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Correspondence to Lisa Mosconi Ph.D. .

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Editors and Affiliations

  1. Pharmacology, Temple University, Philadelphia, Pennsylvania, USA

    Domenico Praticὸ

  2. Istituto di Gerontologia e Geriatria, Università degli Studi di Perugia, Perugia, Italy

    Patrizia Mecocci

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Mosconi, L., Murray, J., McHugh, P., de Leon, M. (2013). Brain Hypometabolism, Oxidative Stress, Maternal Transmission, and Risk of Late-Onset Alzheimer’s Disease. In: Praticὸ, D., Mecocci, P. (eds) Studies on Alzheimer's Disease. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-598-9_10

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