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.

Fluorescent Liposomes for Differential Interactions with Glycosaminoglycans

“…However, it has been reported that the serum concentrations of glycosaminoglycans (uronic acids) increase in Alzheimer’s disease patients (about 8.4 ± 0.8 mg/dL) relative to that of healthy individuals (about 4.6 ± 0.5 mg/dL). 6 Chondroitin sulfate concentration in the serum increases from about 0.58 mg/dL (healthy individuals) to about 2.36 mg/dL for Alzheimer’s disease patients. 6 The LDA analysis indicated that the pyranine-containing liposomes are capable of distinguishing different GAGs at 100 nM and 50 nM concentrations.…”

“…6 Chondroitin sulfate concentration in the serum increases from about 0.58 mg/dL (healthy individuals) to about 2.36 mg/dL for Alzheimer’s disease patients. 6 The LDA analysis indicated that the pyranine-containing liposomes are capable of distinguishing different GAGs at 100 nM and 50 nM concentrations. It follows that the pyranine liposomes has the capability to distinguish the GAGs in a very dilute human serum from an Alzheimer’s disease patient (diluted 10 4 times).…”

“…4,5 The serum concentrations of glycosaminoglycans (uronic acids and chondroitin sulfate) increase considerably in Alzheimer’s disease patients relative to that of healthy individuals. 6 The urine GAG concentrations are also elevated for patients with various types of metastatic cancers, 7–9 and for children with acute urinary tract infections. 10 …”

Effects of taurine on plasma and liver lipids, erythrocyte ouabain sensitive Na efflux and platelet aggregation in Sprague Dawley rats

“…In vitro cholesterol enrichment of human erythrocyte caused an enzymatic inhibition of Na-K ATPase and decreased Na Efflux (Lijnen et al, 1995). Kurup et al (2003) reported that plasma HMG CoA reductase activity was inversely correlated with erythrocyte membrane Na K ATPase in Alzheimer patients. Tranquilli et al (2004) observed that higher cholesterol/phospholipid ratio was correlated with the reduced erythrocyte Na-K ATPase in pregnant women.…”

The Emerging Role of Coenzyme Q-10 in Aging, Neurodegeneration, Cardiovascular Disease, Cancer and Diabetes Mellitus

“…Coenzyme Q-10 has been found to be significantly increased in most regions of the brain in patients with Alzheimer's disease (Edlund et al, 1992. A reduction in serum ubiquinone deficiency related mitochondrial dysfunction could contribute to the etiology and pathology of Alzheimer's disease (Kurup and Kurup, 2003). Decreased mRNA expression of NADH dehydrogenase-4 and NADH dehydrogenase-15 was found in the hippocampus and inferior parietal lobe of the brains of patients with Alzheimer's disease.…”