Ketone Bodies as a Therapeutic for Alzheimer's Disease

Strittmatter, 1996, Apolipoprotein E and Alzheimer's disease, Annu Rev Neurosci, 19, 53, 10.1146/annurev.ne.19.030196.000413 Mosconi, 2007, Early detection of Alzheimer's disease using neuroimaging, Exp Gerontol, 42, 129, 10.1016/j.exger.2006.05.016 Clarke, 1994, Circulation and energy metabolism of the brain, 645 Shulman, 2004, Energetic basis of brain activity: implications for neuroimaging, Trends Neurosci, 27, 489, 10.1016/j.tins.2004.06.005 Raichle, 2006, Brain work and brain imaging, Annu Rev Neurosci, 29, 449, 10.1146/annurev.neuro.29.051605.112819 Buckner, 2008, The brain's default network: anatomy, function, and relevance to disease, Ann N Y Acad Sci, 1124, 1, 10.1196/annals.1440.011 Kety, 1994, Cerebral blood flow and metabolism in schizophrenia, Am J Psychiatry, 151, 203 Dwyer, 2002, Expression, regulation, and functional role of glucose transporters (GLUTs) in brain, 159 Wang, 2005, Glut-1 deficiency syndrome: clinical, genetic, and therapeutic aspects, Ann Neurol, 57, 111, 10.1002/ana.20331 Seidner, 1998, GLUT-1 deficiency syndrome caused by haploinsufficiency of the blood-brain barrier hexose carrier, Nat Genet, 18, 188, 10.1038/ng0298-188 de Leon, 1983, Positron emission tomographic studies of aging and Alzheimer disease, AJNR Am J Neuroradiol, 4, 568 Reiman, 1996, Preclinical evidence of Alzheimer's disease in persons homozygous for the epsilon 4 allele for apolipoprotein E, N Engl J Med, 334, 752, 10.1056/NEJM199603213341202 Small, 2000, Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer's disease, Proc Natl Acad Sci U S A, 97, 6037, 10.1073/pnas.090106797 Buckner, 2005, Molecular, structural, and functional characterization of Alzheimer's disease: evidence for a relationship between default activity, amyloid, and memory, J Neurosci, 25, 7709, 10.1523/JNEUROSCI.2177-05.2005 Reiman, 2004, Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer's dementia, Proc Natl Acad Sci U S A, 101, 284, 10.1073/pnas.2635903100 Corder, 1997, No difference in cerebral glucose metabolism in patients with Alzheimer disease and differing apolipoprotein E genotypes, Arch Neurol, 54, 273, 10.1001/archneur.1997.00550150035013 Hirono, 2002, The effect of APOE epsilon4 allele on cerebral glucose metabolism in AD is a function of age at onset, Neurology, 58, 743, 10.1212/WNL.58.5.743 Mosconi, 2004, Brain metabolic decreases related to the dose of the ApoE e4 allele in Alzheimer's disease, J Neurol Neurosurg Psychiatry, 75, 370, 10.1136/jnnp.2003.014993 Lehtovirta, 1998, Longitudinal SPECT study in Alzheimer's disease: relation to apolipoprotein E polymorphism, J Neurol Neurosurg Psychiatry, 64, 742, 10.1136/jnnp.64.6.742 Mahley, 2006, Apolipoprotein (apo) E4 and Alzheimer's disease: unique conformational and biophysical properties of apoE4 can modulate neuropathology, Acta Neurol Scand Suppl, 185, 8, 10.1111/j.1600-0404.2006.00679.x Atamna, 2007, Mechanisms of mitochondrial dysfunction and energy deficiency in Alzheimer's disease, Mitochondrion, 7, 297, 10.1016/j.mito.2007.06.001 Veech, 2001, Ketone bodies, potential therapeutic uses, IUBMB Life, 51, 241, 10.1080/152165401753311780 Liang, 2008, Alzheimer's disease is associated with reduced expression of energy metabolism genes in posterior cingulate neurons, Proc Natl Acad Sci U S A, 105, 4441, 10.1073/pnas.0709259105 Gabuzda, 1994, Inhibition of energy metabolism alters the processing of amyloid precursor protein and induces a potentially amyloidogenic derivative, J Biol Chem, 269, 13623, 10.1016/S0021-9258(17)36875-8 Velliquette, 2005, Energy inhibition elevates beta-secretase levels and activity and is potentially amyloidogenic in APP transgenic mice: possible early events in Alzheimer's disease pathogenesis, J Neurosci, 25, 10874, 10.1523/JNEUROSCI.2350-05.2005 Calon, 2007, Neuroprotective action of omega-3 polyunsaturated fatty acids against neurodegenerative diseases: evidence from animal studies, Prostaglandins Leukot Essent Fatty Acids, 77, 287, 10.1016/j.plefa.2007.10.019 Henderson, 2004, High carbohydrate diets and Alzheimer's disease, Med Hypotheses, 62, 689, 10.1016/j.mehy.2003.11.028 Owen, 1967, Brain metabolism during fasting, J Clin Invest, 46, 1589, 10.1172/JCI105650 Taggart, 2005, (D)-beta-Hydroxybutyrate inhibits adipocyte lipolysis via the nicotinic acid receptor PUMA-G, J Biol Chem, 280, 26649, 10.1074/jbc.C500213200 Lardy, 1945, The metabolism of bovine epididymal spermatazoa, Arch Biochem, 6, 41 Lardy, 1945, Studies of fat and carbohydrate oxidation in mammalian spermatozoa, Arch Biochem, 6, 53 Sato, 1995, Insulin, ketone bodies, and mitochondrial energy transduction, Faseb J, 9, 651, 10.1096/fasebj.9.8.7768357 Tieu, 2003, D-beta-hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease, J Clin Invest, 112, 892, 10.1172/JCI200318797 Gasior, 2006, Neuroprotective and disease-modifying effects of the ketogenic diet, Behav Pharmacol, 17, 431, 10.1097/00008877-200609000-00009 Prins, 2008, Cerebral metabolic adaptation and ketone metabolism after brain injury, J Cereb Blood Flow Metab, 28, 1, 10.1038/sj.jcbfm.9600543 Finn, 2005, Ketone bodies stimulate chaperone-mediated autophagy, J Biol Chem, 10.1074/jbc.M502456200 Martinez-Vicente, 2007, Autophagy and neurodegeneration: when the cleaning crew goes on strike, Lancet Neurol, 6, 352, 10.1016/S1474-4422(07)70076-5 Stokin, 2006, Axonal transport and Alzheimer's disease, Annu Rev Biochem, 75, 607, 10.1146/annurev.biochem.75.103004.142637 Freeman, 2006, The ketogenic diet: from molecular mechanisms to clinical effects, Epilepsy Res, 68, 145, 10.1016/j.eplepsyres.2005.10.003 Klepper, 2005, Seizure control and acceptance of the ketogenic diet in GLUT1 deficiency syndrome: a 2- to 5-year follow-up of 15 children enrolled prospectively, Neuropediatrics, 36, 302, 10.1055/s-2005-872843 Zhao, 2006, A ketogenic diet as a potential novel therapeutic intervention in amyotrophic lateral sclerosis, BMC Neurosci, 7, 29, 10.1186/1471-2202-7-29 Prins, 2005, Age-dependent reduction of cortical contusion volume by ketones after traumatic brain injury, J Neurosci Res, 82, 413, 10.1002/jnr.20633 Vanitallie, 2005, Treatment of Parkinson disease with diet-induced hyperketonemia: a feasibility study, Neurology, 64, 728, 10.1212/01.WNL.0000152046.11390.45 Van der Auwera, 2005, A ketogenic diet reduces amyloid beta 40 and 42 in a mouse model of Alzheimer's disease, Nutr Metab (Lond), 2, 28, 10.1186/1743-7075-2-28 Moechars, 1999, Early phenotypic changes in transgenic mice that overexpress different mutants of amyloid precursor protein in brain, J Biol Chem, 274, 6483, 10.1074/jbc.274.10.6483 Ho, 2004, Diet-induced insulin resistance promotes amyloidosis in a transgenic mouse model of Alzheimer's disease, Faseb J, 18, 902, 10.1096/fj.03-0978fje Levin-Allerhand, 2002, Increased amyloid- levels in APPSWE transgenic mice treated chronically with a physiological high-fat high-cholesterol diet, J Nutr Health Aging, 6, 315 Feinman, 2005, When is a high fat diet not a high fat diet?, Nutr Metab (Lond), 2, 27, 10.1186/1743-7075-2-27 Sullivan, 2004, The ketogenic diet increases mitochondrial uncoupling protein levels and activity, Ann Neurol, 55, 576, 10.1002/ana.20062 Noh, 2006, Acetoacetate protects neuronal cells from oxidative glutamate toxicity, J Neurosci Res, 83, 702, 10.1002/jnr.20736 Suzuki, 2002, Beta-hydroxybutyrate, a cerebral function improving agent, protects rat brain against ischemic damage caused by permanent and transient focal cerebral ischemia, Jpn J Pharmacol, 89, 36, 10.1254/jjp.89.36 Kashiwaya, 2000, D-beta-hydroxybutyrate protects neurons in models of Alzheimer's and Parkinson's disease, Proc Natl Acad Sci U S A, 97, 5440, 10.1073/pnas.97.10.5440 Bach, 1982, Medium-chain triglycerides: an update, Am J Clin Nutr, 36, 950, 10.1093/ajcn/36.5.950 Reger, 2004, Effects of beta-hydroxybutyrate on cognition in memory-impaired adults, Neurobiol Aging, 25, 311, 10.1016/S0197-4580(03)00087-3 Craft, 2000, Insulin effects on glucose metabolism, memory, and plasma amyloid precursor protein in Alzheimer's disease differ according to apolipoprotein-E genotype, Ann N Y Acad Sci, 903, 222, 10.1111/j.1749-6632.2000.tb06371.x Reger, 2006, Effects of intranasal insulin on cognition in memory-impaired older adults: modulation by APOE genotype, Neurobiol Aging, 27, 451, 10.1016/j.neurobiolaging.2005.03.016 Risner, 2006, Efficacy of rosiglitazone in a genetically defined population with mild-to-moderate Alzheimer's disease, Pharmacogenomics J, 6, 246, 10.1038/sj.tpj.6500369 Craft, 1998, Cerebrospinal fluid and plasma insulin levels in Alzheimer's disease: relationship to severity of dementia and apolipoprotein E genotype, Neurology, 50, 164, 10.1212/WNL.50.1.164 Halestrap, 1999, The proton-linked monocarboxylate transporter (MCT) family: structure, function and regulation, Biochem J, 343, 281, 10.1042/bj3430281 Froberg, 2001, Expression of monocarboxylate transporter MCT1 in normal and neoplastic human CNS tissues, Neuroreport, 12, 761, 10.1097/00001756-200103260-00030 Robinson, 1980, Physiological roles of ketone bodies as substrates and signals in mammalian tissues, Physiol Rev, 60, 143, 10.1152/physrev.1980.60.1.143 Noh, 2003, The protective effect of a ketogenic diet on kainic acid-induced hippocampal cell death in the male ICR mice, Epilepsy Res, 53, 119, 10.1016/S0920-1211(02)00262-0 Klepper, 2007, GLUT1 deficiency syndrome—2007 update, Dev Med Child Neurol, 49, 707, 10.1111/j.1469-8749.2007.00707.x Massieu, 2003, Acetoacetate protects hippocampal neurons against glutamate-mediated neuronal damage during glycolysis inhibition, Neuroscience, 120, 365, 10.1016/S0306-4522(03)00266-5 Mejia-Toiber, 2006, D-beta-hydroxybutyrate prevents glutamate-mediated lipoperoxidation and neuronal damage elicited during glycolysis inhibition in vivo, Neurochem Res, 31, 1399, 10.1007/s11064-006-9189-5 Maalouf, 2007, Ketones inhibit mitochondrial production of reactive oxygen species production following glutamate excitotoxicity by increasing NADH oxidation, Neuroscience, 145, 256, 10.1016/j.neuroscience.2006.11.065 Masuda, 2005, D-beta-hydroxybutyrate is neuroprotective against hypoxia in serum-free hippocampal primary cultures, J Neurosci Res, 80, 501, 10.1002/jnr.20464 Suzuki, 2001, Effect of beta-hydroxybutyrate, a cerebral function improving agent, on cerebral hypoxia, anoxia and ischemia in mice and rats, Jpn J Pharmacol, 87, 143, 10.1254/jjp.87.143 Prins, 2004, Increased cerebral uptake and oxidation of exogenous beta HB improves ATP following traumatic brain injury in adult rats, J Neurochem, 90, 666, 10.1111/j.1471-4159.2004.02542.x Imamura, 2006, D-beta-hydroxybutyrate protects dopaminergic SH-SY5Y cells in a rotenone model of Parkinson's disease, J Neurosci Res, 84, 1376, 10.1002/jnr.21021 Dardzinski, 2000, Increased plasma beta-hydroxybutyrate, preserved cerebral energy metabolism, and amelioration of brain damage during neonatal hypoxia ischemia with dexamethasone pretreatment, Pediatr Res, 48, 248, 10.1203/00006450-200008000-00021