Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Original Research Article Dement Geriatr Cogn Disord 2006;21:198–204 DOI: 10.1159/000090868 Functional Vitamin E Deficiency in ApoE4 Patients with Alzheimer’s Disease Emilie Mas a–c Anne Marie Dupuy a, b Sylvaine Artero b Florence Portet b, c Jean Paul Cristol a Karen Ritchie b Jacques Touchon b, c a Department of Biochemistry, Lapeyronie Hospital, b INSERM, Unit E361, Epidemiology of Neurodegenerative Pathologies of the Nervous System, c Department of Neurology, Gui de Chauliac Hospital, Montpellier, France Introduction There is now increasing evidence that brain tissue is exposed to oxidative stress during the course of Alzhei- mer’s disease (AD). Brain cells and brain cell metabolism may be affected at all levels; nucleic acid, proteins, lipids and carbohydrates may all be modified by oxidative pro- cesses. The brain is physiologically particularly vulnera- ble to oxidative insult as it contains a high proportion of polyunsaturated fatty acids (20:4, n-6; 22:6, n-3) which are a selective target for free radicals, and its metabolism requires substantial quantities of oxygen. Moreover both Fe and ascorbate, which together may enhance oxidant production and lipid peroxidation, are found in large quantities in brain tissue. This high oxidative insult is further enhanced in the presence of neurodegenerative disorders, especially AD [1–5]. The presence of amyloid  peptide (A ) in amyloid plaques increases reactive ox- ygen species production by exacerbating NADPH oxi- dase activity in microglia [6, 7], by impairing mitochon- drial function and energy supply and by initiating local inflammation. Despite this increased free radical produc- tion, the brain is not highly enriched in antioxidant de- fenses [7–9] . Furthermore, ageing and neurodegenerative Key Words Vitamin E  Apolipoprotein E  Alzheimer’s disease Abstract 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 el- derly subjects. No absolute deficit was observed in plas- ma 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-in- duced 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. Copyright © 2006 S. Karger AG, Basel Accepted: September 28, 2005 Published online: January 11, 2006 J.P. Cristol Department of Biochemistry, Hôpital Lapeyronie 191 Avenue du Doyen Gaston Giraud FR–34295 Montpellier Cédex 5 (France) Tel. +33 467 338 345, Fax +33 467 338 393, E-Mail jp-cristol@chu-montpellier.fr © 2006 S. Karger AG, Basel 1420–8008/06/0213–0198$23.50/0 Accessible online at: www.karger.com/dem