Hostname: page-component-78c5997874-v9fdk Total loading time: 0 Render date: 2024-11-05T11:04:37.222Z Has data issue: false hasContentIssue false

Antioxidant strategies for Alzheimer's disease

Published online by Cambridge University Press:  27 March 2009

Michael Grundman*
Affiliation:
Alzheimer's Disease Cooperative Study, University of California, San Diego, 8950 Villa La Jolla Drive, Suite 2200, La Jolla, California 92037, USA
Patrick Delaney
Affiliation:
Alzheimer's Disease Cooperative Study, University of California, San Diego, 8950 Villa La Jolla Drive, Suite 2200, La Jolla, California 92037, USA
*
*Dr Michael Grundman, fax +1 858 452 3058, email [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Oxidative damage is present within the brains of patients with Alzheimer's disease (AD), and is observed within every class of biomolecule, including nucleic acids, proteins, lipids and carbohydrates. Oxidative injury may develop secondary to excessive oxidative stress resulting from β-amyloid-induced free radicals, mitochondrial abnormalities, inadequate energy supply, inflammation or altered antioxidant defences. Treatment with antioxidants is a promising approach for slowing disease progression to the extent that oxidative damage may be responsible for the cognitive and functional decline observed in AD. Although not a uniformly consistent observation, a number of epidemiological studies have found a link between antioxidant intake and a reduced incidence of dementia, AD and cognitive decline in elderly populations. In AD clinical trials molecules with antioxidant properties such as vitamin E and Ginkgo biloba extract have shown modest benefit. A clinical trial with vitamin E is currently ongoing to determine if it can delay progression to AD in individuals with mild cognitive impairment. Combinations of antioxidants might be of even greater potential benefit for AD, especially if the agents worked in different cellular compartments or had complementary activity (e.g. vitamins E, C and ubiquinone). Naturally-occurring compounds with antioxidant capacity are available and widely marketed (e.g. vitamin C, ubiquinone, lipoic acid, β-carotene, creatine, melatonin, curcumin) and synthetic compounds are under development by industry. Nevertheless, the clinical value of these agents for AD prevention and treatment is ambiguous, and will remain so until properly designed human trials have been performed.

Type
Symposium on ‘Micronutrient supplementation: is there a case?’
Copyright
Copyright © The Nutrition Society 2002

References

Adams, JD Jr, Klaidman, LK, Odunze, IN, Shen, HCMiller, CA (1991) Alzheimer's and Parkinson's disease. Brain levels of glutathione, glutathione disulfide, and vitamin E. Molecular and Chemical Neuropathology 14, 213226.CrossRefGoogle ScholarPubMed
Bachurin, S, Oxenkrug, G, Lermontova, N, Afanasiev, A, Beznosko, B, Vankin, G, Shevtzova, E, Mukhina, TSerkova, T (1999) N-acetylserotonin, melatonin and their derivatives improve cognition and protect against beta-amyloid-induced neurotoxicity. Annals of the New York Academy of Sciences 890, 155166.CrossRefGoogle ScholarPubMed
Balestreri, R, Fontana, LAstengo, F (1987) A double-blind placebo controlled evaluation of the safety and efficacy of vinpocetine in the treatment of patients with chronic vascular senile cerebral dysfunction. Journal of the American Geriatrics Society 35, 425430.CrossRefGoogle ScholarPubMed
Bastianetto, S, Ramassamy, C, Dore, S, Christen, Y, Poirier, JQuirion, R (2000 a) The Ginkgo biloba extract (EGb 761) protects hippocampal neurons against cell death induced by betaamyloid. European Journal of Neuroscience 12, 18821890.CrossRefGoogle ScholarPubMed
Bastianetto, S, Ramassamy, C, Poirier, JQuirion, R (1999) Dehydroepiandrosterone (DHEA) protects hippocampal cells from oxidative stress-induced damage. Molecular Brain Research 66, 3541.CrossRefGoogle ScholarPubMed
Bastianetto, S, Zheng, WHQuirion, R (2000 b) The Ginkgo biloba extract (EGb 761) protects and rescues hippocampal cells against nitric oxide-induced toxicity: involvement of its flavonoid constituents and protein kinase C.. Journal of Neurochemistry 74, 22682277.CrossRefGoogle ScholarPubMed
Bastianetto, S, Zheng, WHQuirion, R (2000 c) Neuroprotective abilities of resveratrol and other red wine constituents against nitric oxide-related toxicity in cultured hippocampal neurons. British Journal of Pharmacology 131, 711720.CrossRefGoogle ScholarPubMed
Beal, MFMatthews, RT (1997) Coenzyme Q10 in the central nervous system and its potential usefulness in the treatment of neurodegenerative diseases. Molecular Aspects of Medicine 18, Suppl, S169S179.Google Scholar
Behl, C, Davis, J, Cole, GMSchubert, D (1992) Vitamin E protects nerve cells from amyloid beta protein toxicity. Biochemical and Biophysical Research Communications 186, 944950.CrossRefGoogle ScholarPubMed
Behl, C, Davis, JB, Lesley, RSchubert, D (1994) Hydrogen peroxide mediates amyloid beta protein toxicity. Cell 77, 817827.CrossRefGoogle ScholarPubMed
Behl, C, Skutella, T, Lezoualc'h, F, Post, A, Widmann, M, Newton, CJHolsboer, F (1997) Neuroprotection against oxidative stress by estrogens: structure-activity relatoinship. Molecular Pharmacology 51, 535541.CrossRefGoogle Scholar
Bereczki, DFekete, I (1999) A systematic review of vinpocetine therapy in acute ischaemic stroke. European Journal of Clinical Pharmacology 55, 349352.CrossRefGoogle ScholarPubMed
Berr, C, Balansard, B, Arnaud, J, Roussel, AMAlpérovitch, A (2000) Cognitive decline is associated with systemic oxidative stress: the EVA study. Etude du Vieillissement Artériel. Journal of the American Geriatrics Society 48, 12851291.CrossRefGoogle ScholarPubMed
Black, JE, Isaacs, KR, Anderson, BJ, Alcantara, AAGreenough, WT (1990) Learning causes synaptogenesis, whereas motor activity causes angiogenesis, in cerebellar cortex of adult rats. Proceedings of the National Academy of Sciences USA 87, 55685572.CrossRefGoogle ScholarPubMed
Borek, C (2001) Antioxidant health effects of aged garlic extract. Journal of Nutrition 131, 1010S1015S.CrossRefGoogle ScholarPubMed
Bourdel-Marchasson, I, Delmas-Beauvieux, MC, Peuchant, E, Richard-Harston, S, Decamps, A, Reignier, B, Emeriau, JPRainfray, M (2001) Antioxidant defences and oxidative stress markers in erythrocytes and plasma from normally nourished elderly Alzheimer patients. Age and Ageing 30, 235241.CrossRefGoogle ScholarPubMed
Breteler, MM (2000) Vascular risk factors for Alzheimer's disease: an epidemiologic perspective. Neurobiology of Aging 21, 153160.CrossRefGoogle ScholarPubMed
Brewer, GJWallimann, TW (2000) Protective effect of the energy precursor creatine against toxicity of glutamate and beta-amyloid in rat hippocampal neurons. Journal of Neurochemistry 74, 19681978.CrossRefGoogle ScholarPubMed
Brooks, JO III, Yesavage, JA, Carta, ABravi, D (1998) Acetyl L-carnitine slows decline in younger patients with Alzheimer's disease: a reanalysis of a double-blind, placebo-controlled study using the trilinear approach. International Psychogeriatrics 10, 193203.CrossRefGoogle ScholarPubMed
Bush, AI, Pettingell, WH, Multhaup, G, de Paradis, M, Vonsattel, JP, Gusella, JF, Beyreuther, K, Masters, CLTanzi, RE (1994) Rapid induction of Alzheimer A beta amyloid formation by zinc. Science 265, 14641467.CrossRefGoogle Scholar
Cheng, DHTang, XC (1998) Comparative studies of huperzine A, E2020, and tacrine on behavior and cholinesterase activities. Pharmacology, Biochemistry and Behaviour 60, 377386.CrossRefGoogle ScholarPubMed
Chopra, M., Fitzsimons, PE, Strain, JJ, Thurnham, DIHoward, AN (2000) Nonalcoholic red wine extract and quercetin inhibit LDL oxidation without affecting plasma antioxidant vitamin and carotenoid concentrations. Clinical Chemistry 46, 11621170.CrossRefGoogle ScholarPubMed
Chyan, YJ, Poeggeler, B, Omar, RA, Chain, DG, Frangione, B, Chiso, JPappolla, MA (1999) Potent neuroprotective properties against the Alzheimer beta-amyloid by an endogenous melatonin-related indole structure, indole-3-propionic acid. Journal of Biological Chemistry 274, 2193721942.CrossRefGoogle ScholarPubMed
Cornett, CR, Markesbery, WREhmann, WD (1998) Imbalances of trace elements related to oxidative damage in Alzheimer's disease brain. Neurotoxicology 19, 339345.Google ScholarPubMed
Daniels, WM, van Rensburg, SJ, van Zyl, JMTaljaard, JJ (1998) Melatonin prevents beta-amyloid-induced lipid peroxidation. Journal of Pineal Research 24, 7882.CrossRefGoogle ScholarPubMed
de Bustos, F, Molina, JA, Jimenez-Jimenez, FJ, Garcia-Redondo, A, Gomez-Escalonilla, C, Porpa-Etessam, J et al. (2000) Serum levels of coenzyme Q10 in patients with Alzheimer's disease. Journal of Neural Transmission 107, 233239.CrossRefGoogle ScholarPubMed
Dechent, P, Pouwels, PJ, Wilken, B, Hanefeld, FFrahm, J (1999) Increase of total creatine in human brain after oral supplementation of creatine-monohydrate. American Journal of Physiology 277, R698R704.Google ScholarPubMed
Deibel, MA, Ehmann, WDMarkesbery, WR (1996) Copper, iron, and zinc imbalances in severely degenerated brain regions in Alzheimer's disease: possible relation to oxidative stress. Journal of the Neurological Sciences 143, 137142.CrossRefGoogle ScholarPubMed
Engelhart, MJ, Ruitenberg, A, Swieten, JC, Witteman, JCM, Hofman, ABreteler, MB (2000) Dietary antioxidants and the risk of dementia. The Rotterdam study. Neurobiology of Aging 21, 203S.CrossRefGoogle Scholar
Fagarasan, MOAisen, PS (1996) IL-1 and anti-inflammatory drugs modulate A beta cytotoxicity in PC12 cells. Brain Research 723, 231234.CrossRefGoogle ScholarPubMed
Fagarasan, MOEfthimiopoulos, S (1996) Mechanism of amyloid beta-peptide (1–42) toxicity in PC12 cells. Molecular Psychiatry 1, 398403.Google ScholarPubMed
Fassbender, K, Simons, M, Bergmann, C, Stroick, M, Lutijohamm, D, Keller, P et al. (2001) Simvastatin strongly reduces levels of Alzheimer's disease beta-amyloid peptides Abeta 42 and Abeta 40 in vitro and in vivo. Proceedings of the National Academy of Sciences USA 10, 10.Google Scholar
Foy, CJ, Passmore, AP, Vahidassr, MD, Young, ISLawson, JT (1999) Plasma chain-breaking antioxidants in Alzheimer's disease, vascular dementia and Parkinson's disease. Quarterly Journal of Medicine 92, 3945.CrossRefGoogle ScholarPubMed
Frautschy, SA, Harris-White, ME, Miller, SA, Kim, P, Jimenez, I, Csizar, E et al. (2000) Prevention of Aβ amyloid peptide infusion-induced behavioral deficits, neuroinflammation and neurodegeneration by dietary anti-inflammatory/antioxidant supplements. Society for Neuroscience 26, 1830.Google Scholar
Friedland, RP, Fritsch, T, Smyth, K, Koss, E, Lerner, AJ, Chen, CH, Petot, GJDebanne, SM (2001) Patients with Alzheimer's disease have reduced activities in midlife compared with healthy control-group members. Proceedings of the National Academy of Sciences USA 98, 34403445.CrossRefGoogle ScholarPubMed
Gabuzda, D, Busciglio, J, Chen, LB, Matsudaira, PYankner, BA (1994) Inhibition of energy metabolism alters the processing of amyloid precursor protein and induces a potentially amyloidogenic derivative. Journal of Biological Chemistry 269, 1362313628.CrossRefGoogle ScholarPubMed
Gonzalez, C, Martin, T, Cacho, J, Brenas, MT, Arroyo, T, Garcia-Berrocal, B, Navajo, JAGonzalez-Buitrago, (1999) Serum zinc, copper, insulin and lipids in Alzheimer's disease epsilon 4 apolipoprotein E allele carriers. European Journal of Clinical Investigation 29, 637642.CrossRefGoogle ScholarPubMed
Good, PF, Werner, P, Hsu, A, Olanow, CWPerl, DP (1996) Evidence of neuronal oxidative damage in Alzheimer's disease. American Journal of Pathology 149, 2128.Google ScholarPubMed
Grant, W (1999) Dietary links to Alzheimer's disease: 1999 update. Journal of Alzheimer's Disease 1, 197201.CrossRefGoogle ScholarPubMed
Grundman, M (2000) Vitamin E and Alzheimer disease: the basis for additional clinical trials. American Journal of Clinical Nutrition 71, 630S636S.CrossRefGoogle ScholarPubMed
Grundman, MThal, TJ (2000) Treatment of Alzheimer's disease: rationale and strategies. Neurologic Clinics 18, 807828.Google ScholarPubMed
Guevara, J, Espinosa, B, Zenteno, E, Vazguez, I, Luna, J, Perry, GMena, R (1998) Altered glycosylation pattern of proteins in Alzheimer disease. Journal of Neuropathology and Experimental Neurology 57, 905914.CrossRefGoogle ScholarPubMed
Gulyas, B, Halldin, C, Karlsson, P, Chou, YH, Swahn, CG, Bonock, P, Paroczai, MFarde, L (1999) Brain uptake and plasma metabolism of [11C]vinpocetine: a preliminary PET study in a cynomolgus monkey. Journal of Neuroimaging 9, 217222.CrossRefGoogle Scholar
Hager, K, Marahrens, A, Kenklies, M, Riederer, PMunch, G (2001) Alpha-lipoic acid as a new treatment option for Alzheimer type dementia. Archives of Gerontology and Geriatrics 32, 275282.CrossRefGoogle Scholar
Hindmarch, I, Fuchs, HHErzigkeit, H (1991) Efficacy and tolerance of vinpocetine in ambulant patients suffering from mild to moderate organic psychosyndromes. International Clinical Psychopharmacology 6, 3143.CrossRefGoogle ScholarPubMed
Hirai, K, Hayako, H, Kato, KMiyamoto, M (1998) Idebenone protects hippocampal neurons against amyloid beta-peptide-induced neurotoxicity in rat primary cultures. Naunyn Schmiedeburgs Archives of Pharmacology 358, 582585.CrossRefGoogle ScholarPubMed
Hossain, MS, Hashimoto, M, Gamoh, SMasumura, S (1999) Antioxidative effects of docosahexaenoic acid in the cerebrum versus cerebellum and brainstem of aged hypercholesterolemic rats. Journal of Neurochemistry 72, 11331138.CrossRefGoogle ScholarPubMed
Huang, X, Cuajungco, MP, Atwood, CS, Moir, RD, Tanzi, REBush, I (2000) Alzheimer's disease, beta-amyloid protein and zinc. Journal of Nutrition 130, 1488S1492S.CrossRefGoogle ScholarPubMed
Isaacs, KR, Anderson, BJ, Alcantara, AA, Black, JEGreenough, WT (1992) Exercise and the brain: angiogenesis in the adult rat cerebellum after vigorous physical activity and motor skill learning. Journal of Cerebral Blood Flow and Metabolism 12, 110119.CrossRefGoogle ScholarPubMed
Jama, JW, Launer, LJ, Witteman, JC, den Breeijen, JH, Breteler, MM, Grobbee, DEHofman, A (1996) Dietary antioxidants and cognitive function in a population-based sample of older persons. The Rotterdam Study. American Journal of Epidemiology 144, 275280.Google Scholar
Jeandel, C, Nicolas, MB, Dubois, F, Nabet-Belleville, F, Pennin, FCuny, G (1989) Lipid peroxidation and free radical scavengers in Alzheimer's disease. Gerontology 35, 275282.CrossRefGoogle ScholarPubMed
Jeyarajah, DR, Kielar, M, Penfield, JLu, CY (1999) Docosahexaenoic acid, a component of fish oil, inhibits nitric oxide production in vitro. Journal of Surgical Research 83, 147150.CrossRefGoogle ScholarPubMed
Jick, H, Zornberg, GL, Jick, SS, Seshadri, SDrachman, DA (2000) Statins and the risk of dementia. Lancet 356, 16271631.CrossRefGoogle ScholarPubMed
Jimenez-Jimenez, FJ, de Bustos, F, Gasalla, TOrti-Pareja, M (1996) Estres oxidativo y sistema nervioso central (oxidative stress in the central nervous system). Neurologia 11, 1322.Google Scholar
Jimenez-Jimenez, FJ, de Bustos, F, Molina, JA, Benito-Leon, J, Tallon-Barranco, A, Gasalla, T, Orti-Pareja, M, Guillaman, F, Rubio, JC, Arenas, JEnriquez-de-Salamanca, R (1997) Cerebrospinal fluid levels of alpha-tocopherol (vitamin E) in Alzheimer's disease. Journal of Neural Transmission 104, 703710.CrossRefGoogle ScholarPubMed
Kalmijn, S, Launer, LJ, Ott, A, Witteman, JC, Hofman, ABreteler, MM (1997) Dietary fat intake and the risk of incident dementia in the Rotterdam Study. Annals of Neurology 42, 776782.CrossRefGoogle ScholarPubMed
Kempermann, G, Kuhn, HGGage, FH (1997) More hippocampal neurons in adult mice living in an enriched environment. Nature 386, 493495.CrossRefGoogle Scholar
Kihara, T, Shimohama, S, Sawada, H, Kimura, J, Kume, T, Kochiyama, H, Maeda, TAkaike, A (1997) Nicotinic receptor stimulation protects neurons against beta-amyloid toxicity. Annals of Neurology 42, 159163.CrossRefGoogle ScholarPubMed
Kim, DS, Park, SYKim, JK (2001) Curcuminoids from Curcuma longa L. (Zingiberaceae) that protect PC12 rat pheochromocytoma and normal human umbilical vein endothelial cells from betaA (1–42) insult. Neuroscience Letters 303, 5761.Google ScholarPubMed
Kim, YC, Kim, SR, Markelonis, GJOh, TH (1998) Ginsenosides Rbl and Rg3 protect cultured rat cortical cells from glutamate-induced neurodegeneration. Journal of Neuroscience Research 53, 426432.3.0.CO;2-8>CrossRefGoogle Scholar
Kyle, DJ, Schaefer, E, Patton, GBeiser, A (1999) Low serum docosahexaenoic acid is a significant risk factor for Alzheimer's dementia. Lipids 34, S245.CrossRefGoogle ScholarPubMed
La Rue, A, Koehler, KM, Wayne, SJ, Chiulli, SJ, Haaland, KYGarry, PJ (1997) Nutritional status and cognitive functioning in a normally aging sample: a 6-y reassessment. American Journal of Clinical Nutrition 65, 2029.CrossRefGoogle Scholar
Le Bars, PL, Kieser, MItil, KZ (2000) A 26-week analysis of a double-blind, placebo-controlled trial of the ginkgo biloba extract EGb 761 in dementia. Dementia Geriatrics and Cognitive Disorders 11, 230237.CrossRefGoogle ScholarPubMed
Lerner, AJ, Mizrahi, EH, Chen, CH, Eckman, C, Younkin, SSiavalas, EL et al. (2000) Relationship of plasma amyloid beta fragments to serum cholesterol, high density lipoprotein, albumin, and apolipoprotein E genotype. Neurology 54, A366.Google Scholar
Liu, F, Lau, BH, Peng, QShah, V (2000) Pycnogenol protects vascular endothelial cells from beta-amyloid-induced injury. Biological and Pharmaceutical Bulletin 23, 735737.CrossRefGoogle ScholarPubMed
Lovell, MA, Ehmann, WD, Butler, SMMarkesbery, WR (1995) Elevated thiobarbituric acid-reactive substances and antioxidant enzyme activity in the brain in Alzheimer's disease. Neurology 45, 15941601.CrossRefGoogle ScholarPubMed
Lovell, MA, Gabbita, SPMarkesbery, WR (1999 a) Increased DNA oxidation and decreased levels of repair products in Alzheimer's disease ventricular CSF. Journal of Neurochemistry 72, 771776.CrossRefGoogle ScholarPubMed
Lovell, MA, Xie, CMarkesbery, WR (1999 b) Protection against amyloid beta peptide toxicity by zinc. Brain Research 823, 8895.CrossRefGoogle ScholarPubMed
Maes, M, DeVos, N, Wauters, A, Demedts, P, Maurits, VW, Neels, H et al. (1999) Inflammatory markers in younger vs elderly normal volunteers and in patients with Alzheimer's disease. Journal of Psychiatric Research 33, 397405.CrossRefGoogle ScholarPubMed
Marcus, DL, Thomas, C, Rodriguez, C, Simberkoff, K, Tsai, JS, Strafaci, JAFreedman, ML (1998) Increased peroxidation and reduced antioxidant enzyme activity in Alzheimer's disease. Experimental Neurology 150, 4044.CrossRefGoogle ScholarPubMed
Mark, RJ, Keller, JN, Kruman, IMattson, MP (1997) Basic FGF attenuates amyloid beta-peptide-induced oxidative stress, mitochondrial dysfunction, and impairment of Na+/K + -ATPase activity in hippocampal neurons. Brain Research 756, 205214.CrossRefGoogle ScholarPubMed
Markesbery, WRLovell, MA (1998) Four-hydroxynonenal, a product of lipid peroxidation, is increased in the brain in Alzheimer's disease. Neurobiology of Aging 19, 3336.CrossRefGoogle ScholarPubMed
Masaki, KH, Losonczy, KZ, Izmirlian, G, Foley, DJ, Ross, GW, Petrovitch, H, Havlik, RWhite, LR (2000) Association of vitamin E and C supplement use with cognitive function and dementia in elderly men. Neurology 54, 12651272.CrossRefGoogle Scholar
Mecocci, P, MacGarvey, UBeal, MF (1994) Oxidative damage to mitochondrial DNA is increased in Alzheimer's disease. Annals of Neurology 36, 747751.CrossRefGoogle ScholarPubMed
Meseguer, I, Molina, JA, Jimenez-Jimenez, FJ, Aguilar, MV, Mateo-Vega, CJ, Gonzalez-Munoz, MJ et al. (1999) Cerebrospinal fluid levels of selenium in patients with Alzheimer's disease. Journal of Neural Transmission 106, 309315.CrossRefGoogle ScholarPubMed
Metcalfe, T, Bowen, DMMuller, DP (1989) Vitamin E concentrations in human brain of patients with Alzheimer's disease, fetuses with Down's syndrome, centenarians, and controls. Neurochemical Research 14, 12091212.CrossRefGoogle ScholarPubMed
Misonou, H, Morishima-Kawashima, MIhara, Y (2000) Oxidative stress induces intracellular accumulation of amyloid beta-protein (Abeta) in human neuroblastoma cells. Biochemistry 39, 69516959.CrossRefGoogle ScholarPubMed
Molina, JA, Jimenez-Jimenez, FJ, Aguilar, MV, Meseguer, I, Mateos-Vega, CJ, Gonzalez-Munoz, MJ et al. (1998) Cerebrospinal fluid levels of transition metals in patients with Alzheimer's disease. Journal of Neural Transmission 105, 479488.CrossRefGoogle ScholarPubMed
Moreira, P, Pereira, C, Santos, MSOliveira, C (2000) Effect of zinc ions on the cytotoxicity induced by the amyloid beta-peptide. Antioxidant Redox Signal 2, 317325.CrossRefGoogle ScholarPubMed
Morris, MC, Evans, DA, Bienias, JL, Wilson, RSTangney, CC (2000) Dietary intake of vitamin C and vitamin E and cognitive decline in a biracial community programme. Neurobiology of Aging 21, S202.CrossRefGoogle Scholar
Morris, MC, Beckett, LA, Scherr, PA, Hebert, LE, Bennett, DA, Field, TSEvans, DA (1998) Vitamin E and vitamin C supplement use and risk of incident Alzheimer disease. Alzheimer Disease and Associated Disorders 12, 121126.CrossRefGoogle ScholarPubMed
Mullaart, E, Boerrigter, ME, Ravid, R, Swaab, DFVijg, J (1990) Increased levels of DNA breaks in cerebral cortex of Alzheimer's disease patients. Neurobiology of Aging 11, 169173.CrossRefGoogle ScholarPubMed
Muller, WE, Romero, FJ, Perovic, S, Pergande, GPialoglou, P (1997) Protection of flupirtine on beta-amyloid-induced apoptosis in neuronal cells in vitro: prevention of amyloidinduced glutathione depletion. Journal of Neurochemistry 68, 23712377.CrossRefGoogle ScholarPubMed
Notkola, IL, Sulkava, R, Pekkanen, J, Erkinjuntti, T, Ehnholm, C, Kivinen, P, Tuomilehto, JNissinen, A (1998) Serum total cholesterol, apolipoprotein E epsilon 4 allele, and Alzheimer's disease. Neuroepidemiology 17, 1420.CrossRefGoogle ScholarPubMed
Nourooz-Zadeh, J, Liu, EH, Yhlen, B, Anggard, EEHalliwell, B (1999) F4-isoprostanes as specific marker of docosahexaenoic acid peroxidation in Alzheimer's disease. Journal of Neurochemistry 72, 734740.CrossRefGoogle ScholarPubMed
Nunomura, A, Perry, G, Pappolla, MA, Wade, R, Hirai, K, Chiba, SSmith, MA (1999) RNA oxidation is a prominent feature of vulnerable neurons in Alzheimer's disease. Journal of Neuroscience 19, 19591964.CrossRefGoogle ScholarPubMed
Oken, BS, Storzbach, DMKaye, JA (1998) The efficacy of Ginkgo biloba on cognitive function in Alzheimer disease. Archives of Neurology 55, 14091415.CrossRefGoogle ScholarPubMed
Olivieri, G, Baysang, G, Meier, F, Muller-Spahn, F, Stahelin, HB, Brockhaus, MBrack, C (2001) N-acetyl-L-cysteine protects SHSY5Y neuroblastoma cells from oxidative stress and cell cytotoxicity: effects on beta-amyloid secretion and tau phosphorylation. Journal of Neurochemistry 76, 224233.Google Scholar
Orgogzo, JM, Dartigues, JF, Lafontr, S, Letenneur, L, Commenges, D, Salamon, R, Renaud, SBreteler, MB (1997) Wine consumption and dementia in the elderly: a prospective community study in the Bordeaux area. Revue Neurologique 153, 185192.Google Scholar
Packer, L, Tritschler, HJWessel, K (1997) Neuroprotection by the metabolic antioxidant alpha-lipoic acid. Free Radical Biology and Medicine 22, 359378.CrossRefGoogle ScholarPubMed
Paleologos, M, Cumming, RGLazarus, R (1998) Cohort study of vitamin C intake and cognitive impairment. American Journal of Epidemiology 148, 4550.CrossRefGoogle ScholarPubMed
Pappolla, MA, Sos, M, Omar, RA, Bick, RJ, Hickson-Bick, DL, Reiter, RJ, Efthimiopoulos, SRobakis, NK (1997) Melatonin prevents death of neuroblastoma cells exposed to the Alzheimer amyloid peptide. Journal of Neuroscience 17, 16831690.CrossRefGoogle Scholar
Pereira, C, Agostinho, POliveira, CR (2000) Vinpocetine attenuates the metabolic dysfunction induced by amyloid betapeptides in PC12 cells. Free Radical Research 33, 497506.CrossRefGoogle ScholarPubMed
Pereira, C, Santos, MSOliveira, C (1999) Involvement of oxidative stress on the impairment of energy metabolism induced by A beta peptides on PC12 cells: protection by antioxidants. Neurobiology of Disease 6, 209219.CrossRefGoogle ScholarPubMed
Perkins, AJ, Hendrie, HC, Callahan, CM, Gao, S, Unverzagt, FW, Xu, Y, Hall, KSHui, SL (1999) Association of antioxidants with memory in a multiethnic elderly sample using the Third National Health and Nutrition Examination Survey. American Journal of Epidemiology 150, 3744.CrossRefGoogle Scholar
Perrig, WJ, Perrig, PStahelin, HB (1997) The relation between antioxidants and memory performance in the old and very old. Journal of the American Geriatrics Society 45, 718724.Google Scholar
Pfefferbaum, A, Adalsteinsson, E, Spielman, D, Sullivan, EVLim, KO (1999) In vivo brain concentrations of N-acetyl compounds, creatine, and choline in Alzheimer disease. Archives of General Psychiatry 56, 185192.CrossRefGoogle ScholarPubMed
Prasad, MR, Lovell, MA, Yatin, M, Dhillon, HMarkesbery, WR (1998) Regional membrane phospholipid alterations in Alzheimer's disease. Neurochemical Research 23, 8188.CrossRefGoogle ScholarPubMed
Pratico, D, Clark, CM, Lee, VM, Trojanowski, JQ, Rokach, JFitzGerald, GA (2000) Increased 8, 12-iso-iPF2alpha-VI in Alzheimer's disease: correlation of a noninvasive index of lipid peroxidation with disease severity. Annals of Neurology 48, 809812.3.0.CO;2-9>CrossRefGoogle ScholarPubMed
Pratico, DDelanty, N (2000) Oxidative injury in diseases of the central nervous system: focus on Alzheimer's disease. American Journal of Medicine 109, 577585.CrossRefGoogle ScholarPubMed
Refolo, LM, Pappolla, MA, Malester, B, LaFrancois, J, Bryant-Thomas, T, Wang, R, Tint, GS, Sambanurti, KDuff, K (2000) Hypercholesterolemia accelerates the Alzheimer's amyloid pathology in a transgenic mouse model. Neurobiology of Disease 7, 321331.CrossRefGoogle Scholar
Rischke, RKrieglstein, J (1990) Effects of vinpocetine on local cerebral blood flow and glucose utilization seven days after forebrain ischemia in the rat. Pharmacology 41, 153160.CrossRefGoogle ScholarPubMed
Riviere, S, Birlouez-Aragon, I, Nourhashemi, FVellas, B (1998) Low plasma vitamin C in Alzheimer patients despite an adequate diet. International Journal of Geriatric Psychiatry 13, 749754.Google ScholarPubMed
Romas, SN, Tang, MX, Berglund, LMayeux, R (1999) APOE genotype, plasma lipids, lipoproteins, and AD in community elderly. Neurology 53, 517521.CrossRefGoogle Scholar
Roth, A, Schaffner, WHertel, C (1999) Phytoestrogen kaempferol (3,4′,5,7-tetrahydroxyflavone) protects PC12 and T47D cells from beta-amyloid-induced toxicity. Journal of Neuroscience Research 57, 399404.3.0.CO;2-W>CrossRefGoogle Scholar
Rottkamp, CA, Nunomura, A, Raina, AK, Sayre, LM, Perry, GSmith, MA (2000) Oxidative stress, antioxidants, and Alzheimer disease. Alzheimer Disease and Associated Disorders 14, S62S66.CrossRefGoogle ScholarPubMed
Rottkamp, CA, Raina, AK, Zhu, X, Gaier, E, Bush, AI, Attwood, CS, Chevion, M, Perry, GSmith, MA (2001) Redox-active iron mediates amyloid-beta toxicity. Free Radical Biology and Medicine 30, 447450.Google ScholarPubMed
Samudralwar, DL, Diprete, CC, Ni, BF, Ehmann, WDMarkesbery, WR (1995) Elemental imbalances in the olfactory pathway in Alzheimer's disease. Journal of the Neurological Sciences 130, 139145.CrossRefGoogle ScholarPubMed
Sano, M, Ernesto, C, Thomas, RG, Klauber, MR, Schafer, K, Grundman, M et al. (1997 a) A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's Disease Cooperative Study. New England Journal of Medicine 336, 12161222.CrossRefGoogle ScholarPubMed
Sano, M, Thomas, RGThal, LJ (1997 b) Alpha-tocopherol and Alzheimer's disease. New England Journal of Medicine 337, 573.Google Scholar
Schippling, S, Kontush, A, Arlt, S, Buhmann, C, Sturenburg, HJ, Mann, U, Muller-Thomsen, TBeisiegel, U (2000) Increased lipoprotein oxidation in Alzheimer's disease. Free Radical Biology and Medicine 28, 351360.CrossRefGoogle ScholarPubMed
Schmidt, R, Hayn, M, Reinhart, B, Roob, G, Schmidt, H, Schumacher, M, Watzinger, NLauner, LJ (1998) Plasma antioxidants and cognitive performance in middle-aged and older adults: results of the Austrian Stroke Prevention Study. Journal of the American Geriatrics Society 46, 14071410.CrossRefGoogle ScholarPubMed
Sinclair, AJ, Bayer, AJ, Johnston, J, Warner, CMaxwell, SR (1998) Altered plasma antioxidant status in subjects with Alzheimer's disease and vascular dementia. International Journal of Geriatric Psychiatry 13, 840845.3.0.CO;2-R>CrossRefGoogle ScholarPubMed
Smith, MA, Perry, G, Richey, PL, Sayre, LM, Anderson, VE, Beal, MFKowall, N (1996) Oxidative damage in Alzheimer's. Nature 382, 120121.CrossRefGoogle ScholarPubMed
Smith, MA, Richey Harris, PL, Sayre, LM, Beckman, JSPerry, G (1997) Widespread peroxynitrite-mediated damage in Alzheimer's disease. Journal of Neuroscience 17, 26532657.CrossRefGoogle ScholarPubMed
Smith, MA, Rottkamp, CA, Nunomura, A, Raina, AKPerry, G (2000) Oxidative stress in Alzheimer's disease. Biochimica et Biophysica Acta 1502, 139144.CrossRefGoogle ScholarPubMed
Soderberg, M, Edlund, C, Alafuzoff, I, Kristensson, KDallner, G (1992) Lipid composition in different regions of the brain in Alzheimer's disease/senile dementia of Alzheimer's type. Journal of Neurochemistry 59, 16461653.CrossRefGoogle ScholarPubMed
Soderberg, M, Edlund, C, Kristensson, KDallner, G (1991) Fatty acid composition of brain phospholipids in aging and in Alzheimer's disease. Lipids 26, 421425.CrossRefGoogle ScholarPubMed
Sparks, DL, Martin, TA, Gross, DRHunsaker, JC 3rd (2000) Link between heart disease, cholesterol, and Alzheimer's disease: a review. Microscopy Research and Technique 50, 287290.Google ScholarPubMed
Subhan, ZHindmarch, I (1985) Psychopharmacological effects of vinpocetine in normal healthy volunteers. European Journal of Clinical Pharmacology 28, 567571.CrossRefGoogle ScholarPubMed
Subramaniam, R, Koppal, T, Green, M, Yatin, S, Jordan, B, Drake, JButterfield, DA (1998) The free radical antioxidant vitamin E protects cortical synaptosomal membranes from amyloid betapeptide(25–35) toxicity but not from hydroxynonenal toxicity: relevance to the free radical hypothesis of Alzheimer's disease. Neurochemical Research 23, 14031410.CrossRefGoogle ScholarPubMed
Suh, SW, Jensen, KB, Jensen, MS, Silva, DS, Kesslak, PJ, Danscher, GFrederickson, CJ (2000) Histochemically-reactive zinc in amyloid plaques, angiopathy, and degenerating neurons of Alzheimer's diseased brains. Brain Research 852, 274278.CrossRefGoogle ScholarPubMed
Svensson, ALNordberg, A (1998) Tacrine and donepezil attenuate the neurotoxic effect of A beta(25–35) in rat PC12 cells. Neuroreport 9, 15191522.CrossRefGoogle ScholarPubMed
Tarnopolsky, MABeal, MF (2001) Potential for creatine and other therapies targeting cellular energy dysfunction in neurological disorders. Annals of Neurology 49, 561574.CrossRefGoogle ScholarPubMed
Terano, T, Fujishiro, S, Ban, T, Yamamoto, K, Tanaka, T, Noguchi, Y, Tamura, Y, Yazawa, KHirayama, T (1999) Docosahexaenoic acid supplementation improves the moderately severe dementia from thrombotic cerebrovascular diseases. Lipids 34, S345S346.CrossRefGoogle ScholarPubMed
Thal, LJ, Calvani, M, Amato, ACarta, A (2000) A 1 -year controlled trial of acetyl-l-carnitine in early-onset AD. Neurology 55, 805810.CrossRefGoogle ScholarPubMed
Thal, LJ, Carta, A, Clarke, WR, Ferris, SH, Friedland, RP, Petersen, RC et al. (1996) A 1-year multicenter placebo-controlled study of acetyl-L-carnitine in patients with Alzheimer's disease. Neurology 47, 705711.CrossRefGoogle ScholarPubMed
Thal, LJ, Salmon, DP, Lasker, B, Bower, DKlauber, MR (1989) The safety and lack of efficacy of vinpocetine in Alzheimer's disease. Journal of the American Geriatrics Society 37, 515520.Google ScholarPubMed
Vitek, MP, Bhattacharya, K, Glendening, JM, Stopa, E, Vlassara, H, Bucala, R, Manogue, KCerami, A (1994) Advanced glycation end products contribute to amyloidosis in Alzheimer disease. Proceedings of the National Academy of Sciences USA 91, 47664770.CrossRefGoogle ScholarPubMed
Wang, TTang, XC (1998) Reversal of scopolamine-induced deficits in radial maze performance by (−)-huperzine A: comparison with E2020 and tacrine. European Journal of Pharmacology 349, 137142.CrossRefGoogle ScholarPubMed
Wei, H, Leeds, PR, Qian, Y, Wei, W, Chen, RChuang, D (2000) Beta-amyloid peptide-induced death of PC 12 cells and cerebellar granule cell neurons is inhibited by long-term lithium treatment. European Journal of Pharmacology 392, 117123.Google ScholarPubMed
Wesnes, KA, Ward, T, McGinty, APetrini, O (2000) The memory enhancing effects of a Ginkgo biloba/Panax ginseng combination in healthy middle-aged volunteers. Psychopharmacology (Berlin) 152, 353361.CrossRefGoogle ScholarPubMed
Wolozin, B, Kellman, W, Celesia, GSiegel, G (1999) Decreased prevalence of Alzheimer's disease associated with HMG-CoA reductase inhibitors. Journal of the Neurological Sciences 25, 16(13.9).Google Scholar
Xiao, QX, Wang, R, Han, YFTang, XC (2000 a) Protective effects of hyperzine A on beta-amyloid 25–35 induced oxidative injury in rat pheochromocytoma cells.. Neuroscience Letters 286, 155158.CrossRefGoogle Scholar
Xiao, QX, Wang, RTang, XC (2000 b) Huperzine A and tacrine attenuate beta-amyloid peptide-induced oxidative injury. Journal of Neuroscience Research 61, 564569.Google ScholarPubMed
Xu, SS, Gao, ZX, Weng, Z, Du, ZM, Xu, WA, Yang, JS, Zhang, ML, Tong, ZH, Fang, YSChai, XS (1995) Efficacy of tablet huperzine-A on memory, cognition, and behavior in Alzheimer's disease. Chung Kuo Yao Li Hsueh Pao 16, 391395.Google ScholarPubMed
Yallampalli, S, Micci, MATaglialatela, G (1998) Ascorbic acid prevents beta-amyloid-induced intracellular calcium increase and cell death in PC12 cells. Neuroscience Letters 251, 105108.CrossRefGoogle ScholarPubMed
Yan, JJ, Cho, JY, Kim, HS, Kim, KL, Jung, JS, Huh, SO, Suh, HW, Kim, YHSong, DK (2001) Protection against beta-amyloid peptide toxicity in vivo with long-term administration of ferulic acid. British Journal of Pharmacology 133, 8996.CrossRefGoogle ScholarPubMed
Yan, SD, Chen, X, Schmidt, AM, Brett, J, Godman, G, Zou, YS, Scott, CW, Caputo, C, Frappier, TSmith, MA (1994) Glycated tau protein in Alzheimer disease: a mechanism for induction of oxidant stress. Proceedings of the National Academy of Sciences USA 91, 77877791.CrossRefGoogle ScholarPubMed
Yao, Z, Drieu, KPapadopoulos, V (2001) The Ginkgo biloba extract EGb 761 rescues the PC12 neuronal cells from betaamyloid-induced cell death by inhibiting the formation of betaamyloid-derived diffusible neurotoxic ligands. Brain Research 889, 181190.CrossRefGoogle ScholarPubMed
Yatin, SM, Yatin, M, Aulick, T, Ain, KBButterfield, DA (1999) Alzheimer's amyloid β-peptide associated free radicals increase rat embryonic neuronal polyamine uptake and ornithine decarboxylase activity: protective effect of vitamin E. Neuroscience Letters 263, 1720.CrossRefGoogle ScholarPubMed
Ye, JW, Cai, JX, Wang, LMTang, XC (1999) Improving effects of huperzine A on spatial working memory in aged monkeys and young adult monkeys with experimental cognitive impairment. Journal of Pharmacology and Experimental Therapeutics 288, 814819.Google Scholar
Zaman, Z, Roche, S, Fielden, P, Frost, PG, Niriella, DCCayley, AC (1992) Plasma concentrations of vitamins A and E and carotenoids in Alzheimer's disease. Age and Ageing 21, 9194.CrossRefGoogle Scholar
Zhang, RW, Tang, XC, Han, YY, Sang, GW, Zhang, YD, Ma, YX, Zhang, CLYang, RM (1991) Drug evaluation of huperzine A in the treatment of senile memory disorders. Chung Kuo Yao Li Hsueh Pao 12, 250252.Google ScholarPubMed
Zhou, Y, Gopalakrishnan, VRichardson, JS (1996) Actions of neurotoxic beta-amyloid on calcium homeostasis and viability of PC 12 cells are blocked by antioxidants but not by calcium channel antagonists. Journal of Neurochemistry 67, 14191425.CrossRefGoogle Scholar
Zhou, YRichardson, JS (1996) Cholesterol protects PC12 cells from beta-amyloid induced calcium disordering and cytotoxicity. Neuroreport 7, 24872490.CrossRefGoogle ScholarPubMed