Sporadic Alzheimer's disease: the starving brain

Journal of Alzheimer's Disease : JAD
M Mamelak

Abstract

A reduction in cerebral glucose utilization is one of the earliest signs of Alzheimer's disease. Although the exact cause of this reduction is not known, gathering evidence suggests that it is part of a complex metabolic adaptation to oxidative stress during which glycolysis and oxidative phosphorylation are turned down, glucose metabolism is shifted to the pentose phosphate pathway to generate antioxidant reducing factors such as nicotinamide adenine dinucleotide phosphate (NADPH) and glutathione, and the gamma-aminobutyric acid (GABA) shunt is activated to provide glutamate as an alternate source of energy. In the face of these adaptive metabolic changes, the Alzheimer brain runs short of energy and begins to digest itself. The very early induction of macroautophagy attests to the search for nutrients. In clinical trials, antioxidants alone have not been effectively able to influence the course of the disease as these agents do not meet the energy and nutritional requirements of the brain. Evidence is presented that gammahydroxybutyrate, a natural product of the GABA shunt, can provide the necessary energy, carbon, and antioxidant power and that its use may be able to delay the onset and progress of Alzheimer's disease.

Citations

Feb 3, 2016·Frontiers in Synaptic Neuroscience·Melanie LaßekWalter Volknandt
Jul 28, 2016·Frontiers in Molecular Neuroscience·Stephen C CunnaneChristian-Alexandre Castellano
Feb 6, 2018·Molecular Neurobiology·Joan Francesc MirDolors Serra
Jan 26, 2018·Neurology and Therapy·Mortimer Mamelak
Jun 7, 2019·Nutrition & Metabolism·Fiona H McLeanLynda M Williams
Jan 15, 2016·Annals of the New York Academy of Sciences·Stephen C CunnaneChristian-Alexandre Castellano
Mar 27, 2015·Nature Neuroscience·Costantino Iadecola
Apr 21, 2020·Journal of Alzheimer's Disease : JAD·Samuel T HendersonJudith Walker
May 19, 2017·Frontiers in Aging Neuroscience·Roger J MullinsDimitrios Kapogiannis
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Sep 10, 2019·Frontiers in Neuroscience·Nick BergauAlexander Navarrete Santos
Mar 3, 2021·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Erin R SaitoBenjamin T Bikman

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