title: Hypothalamic digoxin, hemispheric chemical dominance, and Alzheimer's disease.
abstract: This study assessed the changes in the isoprenoid pathway and the consequences of its dysfunction in Alzheimer's disease (AD). The isoprenoid pathway and digoxin status were also studied for comparison in individuals of differing hemispheric dominance to find the role of cerebral dominance in the genesis of Alzheimer's disease. There was elevation in plasma HMG CoA reductase activity, serum digoxin, and dolichol levels, and a reduction in serum magnesium, RBC membrane Na(+)-K+ ATPase activity, and serum ubiquinone levels. Serum tryptophan, serotonin, strychnine, nicotine, and quinolinic acid were elevated, while serum tyrosine, morphine, dopamine, and noradrenaline were decreased. The total serum glycosaminoglycans and glycosaminoglycan fractions, the activity of GAG degrading enzymes and glycohydrolases, carbohydrate residues of glycoproteins, and serum glycolipids were elevated in Alzheimer's disease. HDL cholesterol was reduced and free fatty acids increased. The RBC membrane glycosaminoglycans, hexose, and fucose residues of glycoproteins and cholesterol were reduced, while phospholipid increased. The activity of all free radical scavenging enzymes, concentration of glutathione, alpha tocopherol, iron binding capacity, and ceruloplasmin decreased significantly in Alzheimer's disease, while the concentration of lipid peroxidation products and NO increased. The hypomagnesemia-related NMDA excitotoxicity, ubiquinone deficiency related mitochondrial dysfunction, and altered glycoconjugates/lysosomal stability could contribute to the pathogenesis of Alzheimer's disease. The biochemical patterns, including hyperdigoxinemia observed in Alzheimer's disease, correlated with those obtained in right hemispheric chemical dominance. Right hemispheric chemical dominance is a predisposing factor for Alzheimer's disease.
authors.affiliation: Department of Neurology, Medical College Hospital, Trivandrum, Kerala, India. kvgnair@satyam.net.in
authors.forename: Ravi Kumar
authors.initials: RK
authors.lastname: Kurup
authors.forename: Parameswara Achutha
authors.initials: PA
authors.lastname: Kurup
mesh_terms: D000368:Aged; D000418:Albumins / Q000378:metabolism; D000544:Alzheimer Disease / Q000097:blood / Q000378:metabolism*; D002570:Ceruloplasmin / Q000378:metabolism; D004077:Digoxin / Q000097:blood / Q000378:metabolism*; D004286:Dolichols / Q000097:blood / Q000378:metabolism; D004292:Dominance, Cerebral; D004910:Erythrocyte Membrane / Q000378:metabolism; D005260:Female; D005609:Free Radicals / Q000097:blood / Q000378:metabolism; D007839:Functional Laterality; D006025:Glycosaminoglycans / Q000097:blood; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000097:blood / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism*; D007501:Iron / Q000378:metabolism; D008247:Lysosomes / Q000201:enzymology; D008274:Magnesium / Q000097:blood / Q000378:metabolism; D008297:Male; D016555:Matched-Pair Analysis; D008875:Middle Aged; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D017378:Quinolinic Acid / Q000097:blood; D012701:Serotonin / Q000097:blood; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014364:Tryptophan / Q000097:blood; D024502:alpha-Tocopherol / Q000097:blood
chemical_list: D000418:Albumins; D004286:Dolichols; D005609:Free Radicals; D006025:Glycosaminoglycans; D012701:Serotonin; D004077:Digoxin; D014364:Tryptophan; D007501:Iron; D006903:Hydroxymethylglutaryl CoA Reductases; D002570:Ceruloplasmin; D010749:Phosphoprotein Phosphatases; D000254:Sodium-Potassium-Exchanging ATPase; D017378:Quinolinic Acid; D024502:alpha-Tocopherol; D008274:Magnesium