CSF cholinesterase activity in Gilles de la Tourette's syndrome.

Cerebrospinal fluid acetylcholinesterase (AChE) activity was studied as a possible marker for central cholinergic neuronal function in seven patients with Gilles de la Tourette's syndrome. No significant differences were found between CSF AChE activity in untreated or haloperidol-treated patients and control populations. These data do not appear to support a pathophysiologic association between the cholinergic system and Gilles de la Tourette's syndrome.

Sustained cholinesterase inhibition in AD patients receiving rivastigmine for 12 months.

OBJECTIVE: To study the long-term dual inhibitory effects of rivastigmine on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in patients with AD. METHODS: Eleven patients with mild AD received rivastigmine for 12 months. Cholinesterase (ChE) activities in the CSF and plasma were assessed colorimetrically. Immunoblot analysis was used to evaluate AChE isoforms. Neuropsychiatric tests were performed throughout the study. RESULTS: At 12 months, the mean dose of rivastigmine was 8.6 mg/d and specific activities of ChE in the CSF were lower than baseline values (by 36% for AChE and 45% for BuChE), correlating with parallel reductions in the plasma (27% for AChE and 33% for BuChE). The reduction of specific activities in the CSF, but not in the plasma, appeared to be dependent on the dose and duration of treatment. Scores of some of the neuropsychological tests associated with memory and attention were correlated with both plasma and CSF AChE and BuChE inhibition for up to 6 months. Immunoblot analysis revealed up-regulation of the "read-through" AChE isoform (AChE-R), whereas levels of the synaptic isoform were unchanged. CONCLUSIONS: Rivastigmine causes persistent inhibition of AChE and BuChE in CSF as well as plasma. The persistent CSF inhibition contrasts with earlier findings after long-term treatment by the reversible ChE inhibitor tacrine, which demonstrated increased AChE activity in the CSF but not in the blood. Rivastigmine's effects on the preferential up-regulation of the AChE-R isoform may have a favorable effect on disease stabilization.

Factors influencing the cholinesterases of cerebrospinal fluid in the anaesthetized cat.

Both acetylcholinesterase and non-specific cholinesterase are found in cerebrospinal fluid and blood plasma of the cat; the ratio of activities acetylcholinesterase/non-specific cholinesterase is about 1.5 in cerebrospinal fluid and 0.15 in plasma. A search was made for factors capable of influencing the concentration of the two cholinesterases in cerebrospinal fluid. Either the ventricular system was perfused with artificial cerebrospinal fluid from a lateral ventricle to the aqueduct, or the atlanto-occipital membrane was punctured and cerebrospinal fluid was collected continuously from the cisterna magna. Factors studied included: (a) procedures affecting the composition or formation of cerebrospinal fluid, such as changes in the ionic constituents of the perfusate, the inhibition of cerebrospinal fluid formation by acetazolamide or ouabain, or the rapid intra-carotid infusion of hypertonic urea; (b) arousal (noise or stimulation of the central ends of the sciatic nerves), or deepening of anaesthesia; (c) changes in blood pressure; (d) central stimulants and depressants, pyrogens, prostaglandins, antagonists of acetylcholine. Whereas most procedures or drugs tested increased the concentration of acetylcholinesterase, some central depressants (e.g. chlorpromazine) reduced, while another (ether) increased the appearance of acetylcholinesterase in the cerebrospinal fluid. The effect of ether was, in all probability, due to damage to the blood-brain barrier. A rise in acetylcholinesterase concentration was obtained upon stimulation of the central ends of the sciatic nerves; this was inhibited by atropine but not by N-methylatropine, indicating that the rise was due to increased nervous activity and not to the circulatory effects of the stimulation, since the changes in blood pressure caused by the stimulation remained the same after atropine administration. Amphetamine or leptazol raised the levels of acetylcholinesterase but it was not possible to determine whether this was due only to increased central nervous activity, since there was invariably leakage through the blood-brain barrier which by itself would be sufficient to produce the effect. A rise in the level of acetylcholinesterase was seen after administration of pyrogen; this was apparently not a simple effect of warming the body, but due to the action of the pyrogen on centers concerned with temperature control, since warming the animal by external heat failed to produce a similar change.(ABSTRACT TRUNCATED AT 400 WORDS)

Beta-amyloid levels predict cholinesterase activity in human cerebrospinal fluid.

There is increasing evidence suggesting that beta-amyloid (Abeta) has a direct influence on cholinergic activity. In particular, Abeta has been shown to induce the expression of acetylcholinesterase in the brains of CT-100-expressing transgenic mice and in cell culture experiments. These data indicate a link exists between Abeta production and acetylcholinesterase expression in the human CNS. To test this hypothesis, Abeta levels and cholinesterase activity were measured in 110 human CSF samples. Abeta levels were found to have a significant and positive correlation with cholinesterase activity. This correlation was particularly strong in individuals > 50 years of age. These data support the hypothesis that Abeta can effect cholinergic activity and that this effect may be enhanced in the elderly.

CSF cholinesterase activity in demented and non-demented subjects.

Samples of cerebrospinal fluid (CSF) were examined, looking mainly at total cholinesterase (ChE) and acetyl-cholinesterase (AChE) levels from 139 living subjects. At the completion of the study, 35 of the 139 patients had died and pathological confirmation of the presence of dementia had been obtained. These results, together with results from other laboratories, provide evidence that a low CSF ChE level presenting in demented patients may indicate a depletion of the brain AChE system, and this may confirm a clinical diagnosis of AD as well as other types of dementia which are associated with an alteration of the brain AChE system. The overlap in the levels of CSF biochemical markers between demented and non-demented subjects which has led to many conflicting reports has always disappointed investigators. It is suggested that some 'control' subjects with CSF ChE activity indistinguishable from that in AD patients may have an abnormal ageing process in their brains (brain at risk), although the symptoms of dementia have not yet been detected. Recognition of a pre-clinical or incubation period is very beneficial for explaining discrepancies in biochemistry and pathology in the literature, and must be considered for both the treatment and the prevention of dementia. The long used treatment, which was designed to inhibit AChE, should no longer be used: treatment must be designed to enhance the activity of the neuronal AChE system, or slow its degeneration.

CSF neurotransmitter markers in Alzheimer's disease.

CSF neurotransmitter markers may reflect neurochemical alterations in Alzheimer's disease (AD). The best studied neurochemical deficit in AD is that of acetylcholine. Both acetylcholinesterase and butyrylcholinesterase activity have been reported to be reduced in some but not all studies of AD CSF. Studies of monoamine metabolites have also been controversial but most authors have found reduced concentrations of CSF HVA, lesser reductions in HIAA and no change in MHPG. CSF GABA concentrations have been found to be reduced in AD. Studies of CSF neuropeptides in AD have shown reduced concentrations of somatostatin and vasopressin, normal concentrations of vasoactive intestinal polypeptide and either normal or decreased concentrations of beta-endorphin and corticotropin releasing factor. Although no individual CSF neurochemical markers are specific for AD it may be possible to develop a profile of several neurochemical markers which will have enhanced specificity.

Cholinesterases in cerebrospinal fluid. Correlations with clinical measures in Alzheimer's disease.

Acetylcholinesterase and butyrylcholinesterase activities in cerebrospinal fluid were measured in 17 patients with Alzheimer's disease and 6 control patients, as potential clinical measures of impaired cholinergic neurotransmission in Alzheimer's disease. The activity of butyrylcholinesterase was decreased in patients with Alzheimer's disease compared to that observed in control patients, but there was overlap between values in the 2 groups. Low butyrylcholinesterase activity was correlated with severity of dementia, memory impairment, and language disorder. Acetylcholinesterase activity was significantly correlated with visual contrast sensitivity, but not with dementia severity, and did not differentiate patients with Alzheimer's disease from control cases. These results suggest that cholinesterases in cerebrospinal fluid are related to brain cholinesterases, and indicate that the activities of acetylcholinesterase and butyrylcholinesterase should be distinguished in studies of cerebrospinal fluid.

Acetyl- and butyrylcholinesterase activity in the cerebrospinal fluid of patients with Parkinson's disease.

In this study we investigated acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities and the molecular forms of these enzymes in the cerebrospinal fluid (CSF) of non-demented and demented Parkinsonian patients and in controls. The ratio of AChE to BChE activity was lower in the CSF of demented patients than in non-demented patients, although AChE and BChE activities and the molecular forms of AChE and BChE were the same in the different groups of patients. AChE activity in CSF did not vary according to the severity or duration of dementia associated with Parkinson's disease or with the disability stage of Parkinson's disease. BChE activity in CSF correlated with these clinical parameters, and patients with cerebral atrophy had higher BChE activity in CSF than those patients without atrophy. These alterations in the BChE activity of CSF may be related to gliosis which occurs in the degenerating brain tissue.

Reduced cholinesterase activity and somatostatin-like immunoreactivity in the cerebrospinal fluid of patients with dementia of the Alzheimer type.

Cholinesterase (ChE) activity and somatostatin-like immunoreactivity (SLI) of the cerebrospinal fluid were determined for 59 patients with dementia of the Alzheimer type (AD/SDAT) and for 19 age-matched control patients with no signs of dementia. Both ChE activities and SLI concentrations of cerebrospinal fluid were reduced significantly in dementia patients compared to the controls. In the AD/SDAT patients cholinesterase and somatostatin-like immunoreactivity levels seemed to be correlated with the severity of dementia. These findings agree with observations of reduced cortical acetylcholinesterase activities and somatostatin values in dementia of the Alzheimer type.

Human cerebrospinal fluid acetylcholinesterase and butyrylcholinesterase. Evidence for identity between the serum and cerebrospinal fluid butyrylcholinesterase.

Human cerebrospinal fluid contained both acetylcholinesterase (EC 3.1.1.7) and butyrylcholinesterase (EC 3.1.1.8) and they were estimated in the presence of selective inhibitors. Butyrylcholinesterase of human cerebrospinal fluid was similar to human serum butyrylcholinesterase in its electrophoretic mobility, glycoprotein nature and tyramine activation of the aryl acylamidase (EC 3.5.1.13) activity exhibited by butyrylcholinesterase. Moreover antibody raised against human serum purified butyrylcholinesterase could completely immunoprecipitate butyrylcholinesterase from human cerebrospinal fluid without affecting acetylcholinesterase. It is suggested that a useful method for the precise determination of acetylcholinesterase in human cerebrospinal fluid would be removal of butyrylcholinesterase by immunoprecipitation using antibody raised against human serum butyrylcholinesterase.

Molecular forms of cholinesterases in CSF of Alzheimer's disease/senile dementia of Alzheimer type patients and matched neurological controls.

Acetylcholinesterase, pseudocholinesterase and their molecular forms were measured in the CSF of patients affected by Alzheimer's disease and of matched neurological controls. Three different molecular forms of ChE were found in the CSF of both groups of patients, but only two of them belonged to 'true' AChE. No differences were found between Alzheimer's disease patients and neurological controls in all the examined parameters.

The effect of ACTH4-9 analog (Org2766) on some cerebrospinal fluid parameters in patients with Alzheimer's disease.

In a double-blind, placebo-controlled study, the central nervous system effects of an ACTH4-9 analog, Org2766 (40 mg/day), in Alzheimer's disease were assessed by measuring cerebrospinal fluid parameters during 6 months' treatment. Somatostatin-like immunoreactivity and cholinesterase activity, which are known to be reduced in cerebrospinal fluid of Alzheimer patients compared with controls, did not change during treatment. As a marker of noradrenergic and dopaminergic systems, we measured dopamine-beta-hydroxylase and homovanillic acid, but both levels were static. These results suggest that Org2766 did not interact with the transmitter systems, which are thought to be disturbed in Alzheimer's disease.

Activities and kinetic properties of lumbar cerebrospinal fluid cholinesterases in relation to clinical diagnosis, severity, and progression of Alzheimer's disease.

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities of lumbar cerebrospinal fluid (CSF) have been measured in seventeen patients with a clinical diagnosis of probable Alzheimer's disease (Prob AD), possible Alzheimer's disease (Poss AD), or dementia of non-Alzheimer aetiology (Non-AD). The three diagnostic groups did not differ with regard to the Km or saturation kinetic properties of AChE and BChE. The CSF AChE activity was significantly higher in Prob AD than in Non-AD patients. The groups did not differ significantly in BChE activity. The ratio of AChE to BChE activity was significantly higher in both the Prob AD and Poss AD groups than in the Non-AD group, and the ranges of values in the Prob AD and Non-AD groups did not overlap. Among patients in the Prob AD group, severity of dementia was correlated with both AChE activity and the AChE/BChE ratio, and progression of dementia over time was also correlated with AChE/BChE. The AChE/BChE ratio correlated more strongly than AChE with severity and progression of dementia in Prob AD patients, and also better distinguished them from Non-AD patients, suggesting that AChE/BChE may be the more useful marker for diagnosis of AD. It is not clear from the results whether AChE/BChE is useful for diagnosis of the complex dementia cases in the Poss AD group.

The significance of the activity of CSF cholinesterases in dementias.

This article reviews the significance of changes in the level of cerebrospinal fluid acetylcholinesterase or cholinesterase in patients with Alzheimer's disease or other dementias. Evidence has shown that the methodology of assaying cerebrospinal fluid acetylcholinesterase or cholinesterase is reliable and the activity of the enzyme is stable. Low acetylcholinesterase or cholinesterase levels presenting in cerebrospinal fluid of a demented individual may confirm the clinical diagnosis of Alzheimer's disease or other organic dementia. A low activity of acetylcholinesterase or cholinesterase existing in cerebrospinal fluid of a non-demented individual may indicate a brain at risk, or that the person is in the preclinical stage of dementia. Recognition of the presence of the preclinical stage may be very beneficial for explaining the real meaning of the 'overlap' in the biochemistry and pathology between dementia and non-dementia, and also very important for prevention and treatment. Therefore, the strategy of prevention and of treatment should no longer be designed to inhibit acetylcholinesterase activity. In contrast, it should be designed to enhance the neuronal acetylcholinesterase activity or to delay the degeneration of brain acetylcholinesterase system.

A comparison of cholinesterase activity of plasma, erythrocytes, and cerebrospinal fluid of sheep, calves, dogs, swine, and rabbits.

Cerebrospinal fluid cholinesterase activity was determined in 5 species of domestic animals. Suitable samples of cerebrospinal fluid could be obtained repeatedly from sheep, calves, and dogs without killing, but not from pigs and rabbits. The cholinesterase activity among erythrocytes, plasma, and cerebrospinal fluid of these species was also compared statistically.

[Electrophoresis of cholinesterases of the cerebrospinal fluid in the Guillain-Barré syndrome]. / Electrophorèse des cholinestérases du liquide céphalorachidien dans le syndrome de Guillain-Barré.

Polyacrylamide gel electrophoresis of cholinesterase from cerebrospinal fluid was performed in 22 patients with Guillain-Barré syndrome. Fifteen of these patients had an abnormal cerebrospinal fluid with emergence of a second electrophoretic migration band corresponding to non-specific cholinesterase. Among 182 patients with a variety of diseases who served as controls, only one presented with this abnormality. From these data the sensitivity and specificity of cerebrospinal fluid cholinesterase electrophoresis were calculated at 68 and 99 percent respectively. The second migration band seems to appear early in the course of the disease and disappears when the patient is cured. Moreover, the occurrence of this band is correlated with the severity of the condition, as shown by a greater number of patients under artificial ventilation and by a longer stay in intensive care unit. Cerebrospinal fluid electrophoresis could be used as a prognosis factor.

[Etiology and pathogenesis of epilepsy in children]. / K voprosu ob étiologii i patogeneze épilepsii u detei.

Under examination there were 420 children suffering from epilepsy. In 230 of them the convulsive seizures appeared during the first year of the life: in most of these children (71%) this was in the presence of perinatal pathology. A genealogical analysis of 112 families, from which 135 epileptic children descended, is presented. Various types of hereditary epilepsy were revealed. An examination of some enzymes contained in the cerebrospinal fluid of the epileptic patients revealed shifts in their metabolism in cases of both hereditary and sporadic epilepsy. This reflects common features of the pathogenesis of those forms.

[Role of the acetylcholine--cholinesterase system in the development of epilepsy]. / O roli sistemy atsetilkholin--kholinésteraza v razvitii épilepsii.

The report pertains to some data on the cholinesterase activity in the blood serum and CSF of 62 patients with epilepsy, in correlation with different clinical characteristics (the severity of the disease, the character of the EEG, frequency of seizures, treatment efficacy, etc). In 86,8% of the cases there was a significant increase in the activity of serum cholinesterase. Increased cholinesterase activity correlated only with pronounced pathological changes in the EEG (reverse correlation) and the efficacy of treatment (direct correlation). After surgical treatment of 9 cases there was a drop in the cholinesterase activity of the blood serum and CSF, which correlated with an improvement in the general state of the patients. On the basis of personal experience, as well as literary data, it is assumed that an increase in the cholinesterase activity in epileptic patients is not related to the main etiological factors of this disease but is rather a secondary change, a peculiar "symptom" of the disease.

Effects of cholinesterase inhibitors on the activities and protein levels of cholinesterases in the cerebrospinal fluid of patients with Alzheimer's disease: a review of recent clinical studies.

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cognitive decline associated with a deficit in cholinergic function. Inhibitors of acetylcholinesterase (AChE) and/or butyrylcholinesterase (BuChE), such as donepezil, galantamine or rivastigmine, are widely prescribed as symptomatic treatments for AD. These agents exhibit a wide variation in their pharmacological properties. Here we review clinical data from 1998 to 2009 investigating the effect of different cholinesterase inhibitor treatments on the levels and activities of cholinesterases in the cerebrospinal fluid (CSF) of AD patients. These studies suggest that treatment with rapidly-reversible cholinesterase inhibitors (e.g. donepezil, galantamine, tacrine) are associated with marked and significant upregulation of AChE activities and protein levels in the CSF of AD patients. In contrast, pseudo-irreversible cholinesterase inhibition (e.g. rivastigmine) is associated with a significant decrease in both CSF AChE and BuChE activities, with no upregulation of CSF protein levels. Additionally, donepezil is associated with a decrease in the level of the AChE-R isoform relative to the synaptic AChE-S isoform, whereas rivastigmine seems to increase this ratio. These findings suggest that these agents exert different effects on CSF cholinesterases. The clinical effects of these pharmacological differences are yet to be fully established.