Respiratory chain enzyme activities in isolated mitochondria of lymphocytes from patients with Alzheimer's disease.

We studied respiratory chain enzyme activities in lymphocyte mitochondria from 33 patients with Alzheimer's disease (AD) and from 30 age- and sex-matched healthy controls. The respiratory chain enzyme activities did not differ significantly between patients and controls. No patient showed any value for respiratory chain enzyme levels below normal range. Values for activities of complexes in the AD group did not correlate with age at onset or duration of the disease. Our finding of normal mitochondrial function in lymphocyte mitochondria suggests that this tissue cannot be used to demonstrate the involvement of oxidative phosphorylation in AD and, thus, to develop a diagnostic test for AD.

Tau protein concentrations in cerebrospinal fluid of non-demented Parkinson's disease patients.

We measured total tau protein concentrations in the cerebrospinal fluid (CSF) of 26 non-demented Parkinson's disease (PD) patients and 25 matched controls. When compared with controls, PD patients had similar CSF tau protein concentrations. These values were not correlated with age, age at onset of PD, duration of PD, scores of the Unified PD Rating Scale (UPDRS), and the Hoehn and Yahr staging, and were not influenced significantly by antiparkinsonian drugs. Our results suggest that CSF tau protein levels are apparently unrelated to the risk of PD.

Cerebrospinal fluid levels of thiamine in patients with Parkinson's disease.

Thiamine is an essential cofactor for several important enzymes involved in brain oxidative metabolism, such as the alpha-ketoglutarate dehydrogenase complex (KGDHC), pyruvate-dehydrogenase complex, and transketolase. The activity of KGDHC is decreased in the substantia nigra or patients with Parkinson's disease (PD). We measured cerebrospinal (CSF) levels of thiamine-diphosphate, thiamine-monophosphate, free thiamine, and total thiamine, using ion-pair reversed phase high performance liquid chromatography, in 24 PD patients and 40 matched controls. The mean CSF levels of thiamine-derivatives did not differ significantly from those of controls, with the exception of lower CSF free thiamine levels in the PD-patient group. PD patients under levodopa therapy had significantly higher CSF thiaminediphosphate and total thiamine than those not treated with this drug. CSF thiamine levels were not correlated with age, age at onset, duration of the disease, scores of the Unified Parkinson Disease Rating Scale of the Hoehn and Yahr staging in the PD group. These results suggest that low CSF free thiamine levels could be related with the risk for PD.

Cerebrospinal fluid levels of alpha-tocopherol in patients with multiple sclerosis.

We compared cerebrospinal fluid (CSF) and serum levels, and the CSF/serum ratio of alpha-tocopherol (vitamin E), measured by HPLC, in 36 patients with multiple sclerosis (MS) and 32 matched controls. The mean CSF vitamin E levels and the CSF/serum vitamin E ratio did not differ significantly between the two study groups. The serum levels of vitamin E and the serum vitamin E/cholesterol ratio were significantly lower in MS patients when compared with controls (P < 0.05 and P < 0.01, respectively). These values were not correlated with age, age at onset and duration of the disease in the patients group. These results suggest that CSF vitamin E concentrations are not a marker of activity of MS activity.

Cerebrospinal fluid carnitine levels in patients with Alzheimer's disease.

We assessed free carnitine (FC) and acylcarnitine esters (AC) in both cerebrospinal fluid (CSF) and plasma from 24 patients with diagnostic criteria for Alzheimer's disease (AD), and from 28 healthy matched-controls. We found no significant correlation between FC and AC levels in CSF. FC and AC levels in CSF did not differ significantly between AD patients and controls, but plasma FC levels were significantly lower in AD patients. CSF and plasma FC and AC levels did not correlate with age, age at onset of AD, duration of AD, and scores of the Minimental State Examination of Folstein. Although these results suggest that CSF carnitine levels are apparently unrelated with the risk for AD, the trend of the FC/AC ratio to be higher in AD patients might suggest the possibility of a lower carnitine acetyltransferase activity in AD, as previously reported in some brain areas.

Cerebrospinal fluid cyclic guanosine 3'5' monophosphate levels in Parkinson's disease.

We measured CSF and plasma levels of cGMP in 22 patients with Parkinson's disease (PD) and in 28 age and sex-matched controls. PD patients had similar plasma cGMP levels than those of controls, although they showed a non-significant trend towards higher CSF cGMP levels (P=0.07). PD patients treated with levodopa showed significantly higher CSF cGMP levels than those not treated with this drug (P<0.01), and controls (P<0.01). However, treatment with dopamine agonists did not influence CSF cGMP levels. Plasma and CSF levels of cGMP did not correlate with age at onset, duration, and severity of PD. These results suggest that changes in the concentration of cGMP in CSF of patients with PD are not related with the disease, but rather with levodopa therapy.

[Calcium, neuronal death and neurological disease]. / Calcio, muerte neuronal y enfermedad neurológica.

Calcium ion (Ca2+) plays a role in several important functions in the central nervous system such as production of action potentials, neurotransmitter release, or neuronal plasticity, etc. However, its excessive influx to neurons due to failure of the mechanisms implicated in the regulation of its intracellular concentration (Ca(2+)-channels, calcium binding proteins), leads to a cascade of events which causes cytotoxicity and neuronal death. Ca2+ mediated toxicity has been implicated in the pathogenesis of neurodegenerative diseases (Parkinson's, Alzheimer's, amyotrophic lateral sclerosis, Huntington's), brain ischemia, epilepsy, cranial trauma, and AIDS-dementia complex. In this article we review the current status of this topic.

[Enzyme complex defects of the mitochondrial respiratory chain]. / Déficits de los complejos enzimáticos de la cadena respiratoria mitocondrial.

The mitochondrial respiratory chain is the final step in oxidative metabolism and plays an essential part in the mechanisms of energy production. It is composed of five enzymatic complexes under the dual control of nuclear and mitochondrial genomes. The disorders caused by respiratory chain defects are heterogeneous, mainly affecting organs and tissues which are functionally dependent on oxidative metabolism, such as brain, muscle, myocardium, kidney and liver. The activity of the enzymatic complexes may be measured in any tissue or organ, but skeletal muscle is usually used since it is post-mitotic and permits correlation with morphological studies. Defects in the electron transport chain may affect one or more complexes. Monoenzymopathies are characteristic of nuclear alterations, particularly if there is phenotype histo-specificity. However, mutations of the structural genes of the mitochondrial DNA (mtDNA) may also produce specific defects. Combined defects are characteristic of mtDNA alterations due to reduced synthesis of mitochondrial proteins.

[Molecular genetics of alterations in the mitochondrial respiratory chain]. / Genética molecular de las alteraciones de la cadena respiratoria mitocondrial.

Mitochondrial biogenesis is the result of the coordinated action of two genomes, nuclear (nDNA) and mitochondrial (mtDNA). Therefore respiratory chain defects are divided into alterations of mtDNA and of nDNA. The former may be due to sporadic isolated deletions and specific duplications and mutations, which are both transmitted maternally. The nDNA disorders are inherited following a mendelian pattern and may affect genes which codify enzymes, genes which take part in the process of importing proteins, or genes involved in intergenomic communication. In the latter case, the alterations are seen in the mtDNA as multiple deletions or depletion. The characteristics of mitochondrial genetics are maternal inheritance, polyplasmia, heteroplasmia, mitotic segregation and threshold effect and largely explain the characteristic phenotype behaviour specific to these changes.

[Serum pro-oxidant and antioxidant factors and risk of Parkinson's disease: population study]. / Factores prooxidantes y antioxidantes séricos y riesgo para enfermedad de Parkinson: estudio poblacional.

INTRODUCTION: Several studies suggested a role of 'oxidative stress' (increased production of prooxidants, antioxidants deficiencies or both) in the pathogenesis of Parkinson's disease. In this study we have measured the serum levels of a number of prooxidant and antioxidant substances to evaluate their possible relation with the risk for Parkinson's disease. PATIENTS AND METHODS: We assessed the serum levels of iron, ferritin, ansferrin, ceruloplasmine, vitamin A, alpha-carotene, beta-carotene, and alpha-tocopherol, in 28 patients with Parkinson's disease and 85 matched controls. All of them were recruited from a population study. RESULTS: None of the values studied differed significantly between the two study groups, and none of them were correlated with age at onset, duration of the disease, scores of the Unified Parkinson Disease Rating Scale or the Hoehn and Yahr staging in the Parkinson's disease group. CONCLUSIONS: These results confirm the previous findings of classic case-control studies, suggesting the absence of relationship of the studied values with the risk for Parkinson's disease.

Tau protein concentrations in cerebrospinal fluid of patients with amyotrophic lateral sclerosis.

OBJECTIVE: To elucidate whether cerebrospinal fluid (CSF) concentrations of the microtubule-associated tau protein are related to the risk for sporadic amyotrophic lateral sclerosis (SALS). PATIENTS/METHODS: We measured tau concentrations in the CSF of 18 patients with SALS and 75 age- and sex-matched controls, using a specific ELISA method. RESULTS: The mean CSF concentrations of tau protein did not differ significantly between SALS patient and control groups, were not influenced by the clinical form (spinal vs bulbar) of ALS, and were not correlated with age, age at onset, and duration of the disease. CONCLUSIONS: CSF tau concentrations are not a biochemical marker of ALS.

Serum levels of coenzyme Q in patients with Lewy body disease.

The purpose of the present study was to compare serum levels of coenzyme Q(10) (CoQ(10)) and the coenzyme Q(10) cholesterol (CoQ(10)/cholesterol) ratio in 18 patients with Lewy body disease (LBD) with 20 matched controls. The mean serum coenzyme Q10 levels in patients with LBD were significantly reduced with respect to control group, however, no differences were found in CoQ(10)/cholesterol ratio between LBD patients and control group. There was no correlation among CoQ(10) and CoQ(10)/cholesterol ratio with age, age of onset, body mass index, duration of the disease or scores of the Mini Mental State Examination, UPDRS and Hoehn and Yahr stage. These results suggest the involvement of this enzimatic system in the pathogenic mechanism of LBD.

Cerebrospinal fluid levels of thiamine in patients with Alzheimer's disease.

Thiamine is an essential cofactor for several important enzymes involved in brain oxidative metabolism, such as the alpha-ketoglutarate dehydrogenase complex (KGDHC), pyruvate-dehydrogenase complex (PDHC), and transketolase. Some investigators reported decreased thiamine-diphosphate levels and decreased activities of KGDHC, pyruvate-dehydrogenase complex and transketolase in the brain tissue of Alzheimer's disease (AD) patients. We measured cerebrospinal (CSF) levels of thiamine-diphosphate, thiamine-monophosphate, free thiamine, and total thiamine, using ion-pair reversed phase high performance liquid chromatography, in 33 patients with sporadic AD and 32 matched controls. The mean CSF levels of thiamine-derivatives did not differ significantly from those of controls, while the mean plasma levels of thiamine-diphosphate, free and total thiamine were significantly lower in the AD-patient group. CSF and plasma thiamine levels were not correlated with age, age at onset, duration of the disease, and scores of the MiniMental State Examination, with the exception of plasma thiamine-diphosphate with MiniMental State Examination (r = 0.41, p < 0.05) in the AD-patients group. CSF and plasma values did not predict dementia progression, assessed with the MiniMental State Examination scores. These results suggest that CSF thiamine levels are not related with the risk for and the progression of AD.

Tau protein concentrations in cerebrospinal fluid of patients with multiple sclerosis.

UNLABELLED: FUNDAMENTALS AND OBJECTIVE: Multiple sclerosis (MS) is the prototype of demyelinating disease, but recently, it has been shown that the existence of axonal lesions contribute to irreversible central nervous system damage in this disease. Tau proteins are considered to be important for maintaining the stability of axonal microtubules involved in the mediation of fast axonal transport of synaptic constituents. There have been reports of increased cerebrospinal fluid (CSF) tau concentrations in patients with MS, and it has been suggested that this could be a marker of axonal damage. The objective of the present study was to elucidate whether CSF tau levels could be a marker of MS activity. PATIENT AND METHODS: We measured tau concentrations in the CSF of 20 patients with MS (nine in the first, seven in the second, one in the fourth exacerbation, and three patients with chronic progressive course) and 32 age- and sex-matched controls, using a specific enzyme-linked immunosorbent assay method. RESULTS: The CSF tau concentrations of patients with MS did not differ from those of controls, and they were not correlated with age at onset and duration of the disease. CONCLUSION: CSF tau concentrations are not a marker of MS activity.

Molecular analysis in Spanish patients with muscle carnitine palmitoyltransferase deficiency.

The most common mutation in muscle carnitine palmitoyltransferase II (CPT II) deficiency is a missense mutation that replaces a leucine for a serine residue at amino acid position 113 of the CPT II protein (S113L). We performed molecular analysis in a group of 14 Spanish patients with CPT II deficiency from ten unrelated families. The S113L mutation was observed in 8 of the 14 patients studied. Seven patients were homozygous for the mutation, 1 patient was heterozygous, and 6 patients did not carry the mutation on either allele. Seven healthy relatives belonging to three different families carried the mutation on one allele. One patient carried the missense mutation that replaces a tyrosine for a serine at amino acid position 628 on one allele. Our data indicate that the S113L is also the most common mutation in Spanish patients with CPT II deficiency in muscle, and that further pathogenic mutations remain to be identified.

Serum levels of beta-carotene, alpha-carotene and vitamin A in patients with Alzheimer's disease.

To elucidate the possible role of carotenoids and vitamin A as risk factors for Alzheimer's disease (AD), we compared serum levels of beta-carotene and alpha-carotene, and vitamin A, measured by isocratic high performance liquid chromatography, of 38 AD patients and 42 controls. The serum levels of alpha-carotene did not differ significantly between AD patients and control groups. However, the serum levels of beta-carotene and vitamin A were significantly lower in the AD-patient group. These values did not correlate to age, age at onset or score on the MiniMental State Examination. Weight and body mass index were significantly lower in AD patients than in controls. These results suggest that low serum beta-carotene concentrations in AD patients could be related to a deficiency in dietary intake of this provitamin, although its possible relationship with risk for AD could not be excluded.

Serum levels of coenzyme Q10 in patients with Parkinson's disease.

We compared serum levels of coenzyme Q10 and the coenzyme Q10/cholesterol ratio in 33 patients with Parkinson's disease (PD) and 31 matched controls. The mean serum coenzyme Q10 levels did not differ significantly between the 2 study groups. Coenzyme Q10 levels were not correlated with age, age at onset, duration of the disease, scores of the Unified Parkinson Disease Rating Scale (UPDRS) or the Hoehn and Yahr staging in the PD group. The coenzyme Q10/cholesterol ratio had a significant correlation (although low) with duration of the disease (r = -0.46), total UPDRS score (r = -0.39), motor examination of the UPDRS (r = 0.45). These values were not influenced significantly by therapy with levodopa or dopamine agonists. The normality of serum coenzyme Q10 and coenzyme Q10/cholesterol ratio suggest that these values are not related with the risk for PD.

Serum levels of coenzyme Q10 in patients with Alzheimer's disease.

We compared serum levels of coenzyme Q10 and the coenzyme Q10/cholesterol ratio in 44 patients with Alzheimer's disease (AD), 17 patients with vascular dementia (VD), and 21 matched controls. The mean serum coenzyme Q10 and cholesterol levels and the coenzyme Q10/cholesterol ratio of patients with AD or VD did not differ significantly from those of controls. Coenzyme Q10 levels and coenzyme Q10/cholesterol ratio of AD or VD patients were not correlated with age, age at onset, duration of the disease or scores of the MiniMental State Examination. These results suggest that these values are not related with the risk for AD or VD.

Cerebrospinal fluid nitrate levels in patients with multiple sclerosis.

It has been suggested that nitric oxide (NO) could be implicated in the pathogenesis of multiple sclerosis (MS). Recently, two groups reported increased cerebrospinal fluid (CSF) nitrate levels (oxidation product that provides an indirect estimation of NO) in MS patients. However, another group did not confirm these findings. We studied the CSF and plasma levels of nitrate with a kinetic cadmium reduction method in 11 MS patients and 25 matched controls. The CSF nitrate levels and the CSF/plasma nitrate ratio did not differ significantly between the two study groups. Plasma nitrate levels were nearly significantly lower in MS patients. CSF and plasma nitrate levels did not correlate with age at onset and duration of the disease in the patient group. These data suggest that measurement of CSF levels of nitrate is not a marker of the activity of MS.