Exp Neurol (2008 Dec)
Cholinergic degeneration and memory loss delayed by vitamin E in a Down syndrome mouse model
Lockrow J, Prakasam A, Huang P, Bimonte-Nelson H, Sambamurti K, Granholm AC.
Department of Neuroscience, and the Center on Aging, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425
Down syndrome (DS) individuals develop several neuropathological hallmarks seen in Alzheimer's disease, including cognitive decline and the early loss of cholinergic markers in the basal forebrain. These deficits are replicated in the Ts65Dn mouse, which contains a partial trisomy of murine chromosome 16, the orthologous genetic segment to human chromosome 21. Oxidative stress levels are elevated early in DS, and may contribute to the neurodegeneration seen in these individuals. We evaluated oxidative stress in Ts65Dn mice, and assessed the efficacy of long-term antioxidant supplementation on memory and basal forebrain pathology. We report that oxidative stress was elevated in the adult Ts65Dn brain, and that supplementation with the antioxidant vitamin E effectively reduced these markers. Also, Ts65Dn mice receiving vitamin E exhibited improved performance on a spatial working memory task and showed an attenuation of cholinergic neuron pathology in the basal forebrain. This study provides evidence that vitamin E delays onset of cognitive and morphological abnormalities in a mouse model of DS, and may represent a safe and effective treatment early in the progression of DS neuropathology.
Clin Genet 55(3): 192-7 (1999 Mar)
Effect of vitamin E on chromosomal aberrations in lymphocytes from patients with Down's syndrome
Pincheira J, Navarrete MH, de la Torre C, Tapia G, Santos MJ
Departamento de Pediatria y Cirugia Infantil, Facultad de Medicina, Universidad de Chile, Santiago
A possible protective effect of vitamin E (DL-alpha-tocopherol) on chromosomal damage was evaluated in lymphocytes from patients with Down's syndrome (DS) and from controls. This included the analysis of the basal and G2 chromosomal aberration frequencies in lymphocytes cultured with and without 100 microM vitamin E. The chromosomal damage in G2 was determined by scoring the number of chromosomal aberrations in lymphocyte cultures treated with 5 mM caffeine, 2 h before harvesting. Vitamin E treatment decreased the basal and G2 chromosomal aberrations both in control and DS lymphocytes. In DS cells, this protective effect, expressed as a decrease in the chromosomal damage, was greater (50%) than in controls (30%). These results suggest that the increment in basal and G2 aberrations yield in DS lymphocytes may be related to the increase in oxidative damage reported in these patients.
Journal of Mental Deficiency Research 32(6): 479-484 (1988 Dec)
Vitamin E and Alzheimer's disease in subjects with Down's syndrome
Jackson, C.V.; Holland, A.J.; Williams, C.A.; Dickerson, J.W.
U Surrey Div of Nutrition & Food Science, Guildford, England
Tested the hypothesis that a low level of serum Vitamin E would be associated with a likelihood of dementia in 24 Ss (aged 30+ yrs) with Down's syndrome. Blood samples were drawn, and evidence of deterioration in self-care skills was assessed. Nine Ss showed evidence of Alzheimer's disease (AD), and 9 did not. Plasma Vitamin E levels measured in Ss with AD were lower than in Ss without AD. It is suggested that there may be an interaction between risk of AD and the protective action of Vitamin E.