Oxidative stress has been implicated in the development of Alzheimer’s disease (AD). Consequently, antioxidant therapies including Vitamin E (VitE) supplementation for both prevention and treatment of neurodegenerative diseases currently appears to be a promising avenue of research. The aim of the present study was to examine the relationship between AD and the ApoE phenotype, lipid parameters and VitE levels in a large cohort of elderly subjects. No absolute deficit was observed in plasma VitE levels. However in AD, ApoE4 is not associated with an increase in total cholesterol (TC) and VitE levels. Moreover, our results suggest that oxidative stress-induced injury and protection by VitE in AD are related to the ApoE phenotype. Our study strongly supports the hypothesis of an impairment of lipophilic antioxidant delivery to neuronal cells in AD leading to a tissular antioxidant deficiency which could facilitate oxidative stress.
© 2006 S. Karger AG, Basel
- Vitamin E
- Apolipoprotein E
- Alzheimer’s disease
- Gsell W, Strein I, Krause U, Riederer P: Neurochemical abnormalities in Alzheimer’s disease and Parkinson’s disease – a comparative review. J Neural Transm Suppl 1997;51:145–159.
- Gsell W, Strein I, Riederer P: The neurochemistry of Alzheimer type, vascular type and mixed type dementias compared. J Neural Transm Suppl 1996;47:73–101.
- Behl C, Sagara Y: Mechanism of amyloid beta protein induced neuronal cell death: current concepts and future perspectives. J Neural Transm Suppl 1997;49:125–134.
- Retz W, Gsell W, Munch G, Rosler M, Riederer P: Free radicals in Alzheimer’s disease. J Neural Transm Suppl 1998;54:221–236.
- Rosler M, Retz W, Thome J, Riederer P: Free radicals in Alzheimer’s dementia: currently available therapeutic strategies. J Neural Transm Suppl 1998;54:211–219.
- Behl C, Davis JB, Lesley R, Schubert D: Hydrogen peroxide mediates amyloid β protein toxicity. Cell 1994;77:817–827.
- Christen Y: Oxidative stress and Alzheimer disease. Am J Clin Nutr 2000;71:621S–629S.
- Floyd RA: Antioxidants, oxidative stress, and degenerative neurological disorders. Proc Soc Exp Biol Med 1999;222:236–245.
- Floyd RA, Hensley K: Oxidative stress in brain aging: implications for therapeutics of neurodegenerative diseases. Neurobiol Aging 2002;23:795–807.
- Simonian NA, Coyle JT: Oxidative stress in neurodegenerative diseases. Annu Rev Pharmacol Toxicol 1996;36:83–106.
- Markesbery WR: Oxidative stress hypothesis in Alzheimer’s disease. Free Radic Biol Med 1997;23:134–147.
- Markesbery WR, Carney JM: Oxidative alterations in Alzheimer’s disease. Brain Pathol 1999;9:133–146.
- Butterfield DA, Yatin SM, Varadarajan S, Koppal T: Amyloid beta-peptide-associated free radical oxidative stress, neurotoxicity, and Alzheimer’s disease. Methods Enzymol 1999;309:746–768.
- Butterfield DA, Drake J, Pocernich C, Castegna A: Evidence of oxidative damage in Alzheimer’s disease brain: central role for amyloid beta-peptide. Trends Mol Med 2001;7:548–554.
- Butterfield DA, Boyd-Kimball D: The critical role of methionine 35 in Alzheimer’s amyloid beta-peptide (1–42)-induced oxidative stress and neurotoxicity. Biochim Biophys Acta 2005;1703:149–156.
- Poirier J: Apolipoprotein E and cholesterol metabolism in the pathogenesis and treatment of Alzheimer’s disease. Trends Mol Med 2003;9:94–101.
- Anderson R, Barnes JC, Bliss TV, Cain DP, Cambon K, Davies HA, Errington ML, Fellows LA, Gray RA, Hoh T, Stewart M, Large CH, Higgins GA: Behavioural, physiological and morphological analysis of a line of apolipoprotein E knockout mouse. Neuroscience 1998;85:93–110.
- Burns MP, Noble WJ, Olm V, Gaynor K, Casey E, LaFrancois J, Wang L, Duff K: Co-localization of cholesterol, apolipoprotein E and fibrillar AB in amyloid plaques. Mol Brain Res 2002;110:119–125.
- Poirier J: Apolipoprotein E, cholesterol transport and synthesis in sporadic Alzheimer’s disease. Neurobiol Aging 2005;26:355–361.
- Beffert U, Aumont N, Dea D, Lussier-Cacan S, Davignon J, Poirier J: Apolipoprotein E isoform-specific reduction of extracellular amyloid in neuronal cultures. Mol Brain Res 1999;68:181–185.
- Dupuy AM, Mas E, Ritchie K, Descomps B, Badiou S, Cristol JP, Touchon J: The relationship between apolipoprotein E4 and lipid metabolism is impaired in Alzheimer’s disease. Gerontology 2001;47:213–218.
- Ramassamy C, Averill D, Beffert U, Bastianetto S, Theroux L, Lussier-Cacan S, Cohn JS, Christen Y, Davignon J, Quirion R, Poirier J: Oxidative damage and protection by antioxidants in the frontal cortex of Alzheimer’s disease is related to the apolipoprotein E genotype. Free Radic Biol Med 1999;27:544–553.
- Montine K, Kim PJ, Olson SJ, Markesbery WR, Montine TJ: 4-Hydroxynonenal pyrrole adducts in human neurodegenerative disease. J Neuropath Exp Neurol 1997;56:866–871.
- Montine K, Recch E, Neely MD, Sidell KR, Olson SJ, Markesbery WR, Montine TJ: Distribution of reducible 4-hydroxynonenel adduct immunoreactivity in Alzheimer disease is associated with Apo E genotype. J Neuropathol Exp Neurol 1998;57:415–425.
- Miyata M, Smith JD: Apolipoprotein allele-specific anti-oxidant activity and effects on cytotoxicity by oxidative insults and beta-amyloid peptides. Nat Genet 1996;14:55–61.
- Lee Y, Aono M, Laskowitz D, Warner DS, Pearlstein RD: Apolipoprotein E protects against oxidative stress in mixed neuronal-glial cell cultures by reducing glutamatetoxicity. Neurochem Int 2004;44:107–118.
- Badiou S, Cristol JP, Morena M, Bosc JY, Carbonneau MA, Dupuy AM, Descomps B, Canaud B: Vitamin E supplementation increases LDL resistance to ex vivo oxidation in hemodialysis patients. Int J Vitam Nutr Res 2003;73:290–296.
- Gey K, Puska P, Jordan P, Moser UK: Inverse correlation between plasma vitamin E and mortality from ischemic heart disease in cross-cultural epidemiology. Am J Clin Nutr 1991;53:326S–334S.
- Jordan P, Brubacher D, Moser U, Stähelin HB, Gey KF: Vitamin E and vitamin A concentrations in plasma adjusted for cholesterol and triglycerides by multiple regression. Clin Chem 1995;41/6:924–927.
- Horwit MK, Harvey CC, Dahm CH Jr, Searcy MT: Relationship between tocopherol and serum lipid levels for determination of nutritional adequacy. Ann N Y Acad Sci 1972;203:223–236.
- Grundman M: Vitamin E and Alzheimer disease: the basis for additional clinical trials. Am J Clin Nutr 2000;71:630S–636S.
- Jeandel C, Nicolai M, Dubois F, Nabet-Belleville F, Penin F, Cuny G: Lipid peroxidation and free radicals scavengers in Alzheimer’s disease. Gerontology 1989;35:275–282.
- Zaman Z, Roche S, Fielden P, Frost PG, Niriella DC, Cayley AC: Plasma concentrations of vitamins A and E and carotenoids in Alzheimer’s disease. Age Aging 1992;21:91–94.
- Jimenez-Jimenez FJ, De Bustos F, Molina JA, Benito-Leon J, Tallon-Barranco A, Gasalla T, Orti-Pareja M, Guillaman F, Rubio JC, Arenas J, Enriquez-de-Salamanca R: Cerebrospinal fluid levels of alpha-tocopherol (vitamin E) in Alzheimer’s disease. J Neural Transm 1997;104:703–710.
- Sinclair AJ, Bayer AJ, Johnston J, Warner C, Maxwell SR: Altered plasma antioxidant status in subjects with Alzheimer’s disease and vascular dementia. Int J Geriatr Psychiatry 1998;13:840–845.
- Foy CJ, Passmore AP, Vahidassr MD, Young IS, Lawson JT: Plasma chain-breaking antioxidants in Alzheimer’s disease, vascular dementia and Parkinson’s disease. Q J Med 1999;92:39–45.
- Bourdel-Marchasson I, Delmas-Beauvieux MC, Peuchant E, Richard-Harston S, Decamps A, Reignier B, Emeriau JP, Rainfray M: Antioxidant defenses and oxidative stress markers in erythrocytes and plasma from normally nourished elderly Alzheimer patients. Age Ageing 2001;30:235–241.
- Riviere S, Birlouez-Aragon I, Nourhashemi F, Vellas B: Low plasma vitamin C in Alzheimer patients despite an adequate diet. Int J Geriatr Psychiatry 1998;13:749–754.
- Schippling S, Kontush A, Arlt S, Buhmann C, Sturenburg HJ, Mann U, Muller-Thomsen T, Beisiegel U: Increased lipoprotein oxidation in Alzheimer’s disease. Free Radic Biol Med 2000;28:351–360.
- Metcalfe T, Bowen DM, Muller DP: Vitamin E concentrations in human brain of patients with Alzheimer’s disease, fetuses with Down’s syndrome, centenarians, and controls. Neurochem Res 1989;14:1209–1212.
- Lodge JK, Hall WL, Jeanes YM, Proteggente AR: Physiological factors influencing vitamin E biokinetics. Ann N Y Acad Sci 2004;1031:60–73.
- Wurtman R: Choline metabolism as a basis for selective vulnerability of cholinergic neurons. Trends Neurosci 1992;15:117–122.
- Romas S, Tang MX, Berglund L, Mayeux R: ApoE genotype, plasma lipids, lipoproteins, and AD in community elderly. Neurology 1999;53:517–521.
- Evans R, Emsley MS, Gao S, Sahota A, Hall KS, Farlow MR, Hendrie H: Serum cholesterol, ApoE genotype, and the risk of Alzheimer’s disease; a population-based study of African Americans. Neurology 2000;54:240–242.
- Wehr H, Parnowski T, Puzynski S, Bednarska-Makaruk M, Bisko M, Kotapka-Minc S, Rodo M, Wolkowska M: Apolipoprotein E genotype and lipid and lipoprotein levels in dementia. Dement Geriatr Cogn Disord 2000;11:70–73.
- Jarvik G, Wijsman EM, Kukull WA, Schellenberg GD, Yu C, Larson EB: Interactions of apolipoprotein E genotype, total cholesterol level, age, and sex in prediction of Alzheimer’s disease: a case-control study. Neurology 1995;45:1092–1096.
- Notkola I, Sulkava R, Pekkanen J, Erkinjuntti T, Ehnholm C, Kivinen P, Tuomilehto J, Nissinen A: Serum cholesterol, apolipoprotein E4 allele, and Alzheimer’s disease. Neuroepidemiology 1998;17:14–20.
- Bonarek M, Barbeger-Gateau P, Letenneur L, Deschamps V, Iron A, Dubroca B, Dartigues JF: Relationships between cholesterol, apolipoprotein E polymorphism and dementia: a cross-sectional analysis from the PAQUID study. Neuroepidemiology 2000;19:141–148.
- De-Andrade F, Larrandaburu M, Callegeri-Jacques SM, Gastaldo G, Hutz MH: Association of apolipoprotein E polymorphism with plasma lipids and Alzheimer’s disease in a southern Brazilian population. Braz J Med Biol Res 2000;33:529–537.
- Fernandes M, Proença MT, Nogueira AJA, Grazina MMM, Oliveira LMV, Fernandes AIP, Santiago B, Santana I, Oliveira CR: Influence of apolipoprotein E genotype on blood redox status of Alzheimer’s disease patients. Int J Mol Med 1999;4:179–186.
- Maezawa I, Jin LW, Woltjer RL, Maeda N, Martin GM, Montine TJ, Montine KS: Apolipoprotein E isoforms and apolipoprotein AI protect from amyloid precursor protein carboxy terminal fragment-associated cytotoxicity. J Neurochem 2004;91:1312–1321.
- Zandi P, Anthony J, Khachaturian A, Stone S, Tschanz D, Norton M, Welsh-Bohmer A, Breitner J: Reduced risk of Alzheimer disease in users of antioxidant vitamin supplement county study. Arch Neurol 2004;61:81–82.
- Morris MC, Evans DA, Bienias JL, Tangney CC, Bennett DA, Aggarwal N, Wilson RS, Scherr PA: Dietary intake of antioxidant nutrients and the risk of incident Alzheimer disease in a biracial community study. JAMA 2002;287:3230–3237.
- Engelhart MJ, Geerlings MI, Ruitenberg A, Van Swieten JC, Hofman A, Witteman JC, Breteler MM: Dietary intake of antioxidants and risk of Alzheimer disease. JAMA 2002;287:3223–3229.
- Morris MC, Beckett LA, Scherr PA, Hebert LE, Bennett DA, Field TS, Evans DA: Vitamin E and vitamin C supplement use and risk of incident Alzheimer disease. Alzheimer Dis Assoc Disord 1998;12:121–126.
- Morris MC, Evans DA, Tangney CC, Bienias JL, Wilson RS, Aggarwal NT, Scherr PA: Relation of the tocopherol forms to incident Alzheimer disease and to cognitive change. Am J Clin Nutr 2005;81:508–514.
- Grodstein F, Fretts R, Lifford K, Resnick N, Curhan G: Association of age, race, and obstetric history with urinary symptoms among women in the Nurses’ Health Study. Am J Obstet Gynecol 2003;189:428–434.
- Quinn JF, Montine KS, Moore M, Morrow JD, Kaye JA, Montine TJ: Suppression of longitudinal increase in CSF F2-isoprostanes in Alzheimer’s disease. J Alzheimers Dis 2004;6:93–97.
- Luchsinger JA, Tang MX, Shea S, Mayeux R: Antioxidant vitamin intake and risk of Alzheimer disease. Arch Neurol 2003;60:203–208.
- Masaki KH, Losoncsy KG, Izmirlian G, Foley DJ, Ross GW, Petrovitch H, Havlik R, White LR: Association of vitamin E and C supplement use with cognitive function and dementia in elderly men. Neurology 2000;55:901–902.
- Petersen RC, Thomas RG, Grundman M, Bennett D, Doody R, Ferris S, Galasko D, Jin S, Kaye J, Levey A, Pfeiffer E, Sano M, van Dyck CH, Thal LJ: Vitamin E and donepezil for the treatment of mild cognitive impairment. N Engl J Med 2005;352:2379–2388.
- Gey KF: Vitamin E plus C and interacting conutrients required for optimal health. A critical and constructive review of epidemiology and supplementation data regarding cardiovascular disease and cancer. Biofactors 1998;7:113–174.
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Accepted: September 28, 2005
Published online: January 11, 2006
Number of Print Pages : 7
Number of Figures : 0, Number of Tables : 2, Number of References : 62
Dementia and Geriatric Cognitive Disorders
Vol. 21, No. 3, Year 2006 (Cover Date: February 2006)
Journal Editor: Chan-Palay, V. (New York, N.Y.)
ISSN: 1420–8008 (print), 1421–9824 (Online)
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