Cerebrospinal Fluid Acetylcholinesterase Research Articles

Cerebrospinal Fluid as a Reflector of Central Cholinergic and Amino Acid Neurotransmitter Activity in Cerebellar Ataxia

Cerebrospinal fluid (CSF) amino acid neurotransmitters, related compounds, and their precursors, choline levels, and acetylcholinesterase activity were measured in the CSF of patients with cerebellar ataxia during a randomized, double-blind, crossover, placebo-controlled clinical trial of physostigmine salicylate. The CSF gamma-aminobutyric acid, methionine, and choline levels, adjusted for age, were significantly lower in patients with cerebellar ataxia compared with controls. Physostigmine selectively reduced the level of CSF isoleucine and elevated the levels of phosphoethanolamine. No change occurred in CSF acetylcholinesterase activity and in the levels of plasma amino compounds in patients with cerebellar ataxia when compared with controls. Median ataxia scores did not statistically differ between placebo and physostigmine nor did functional improvement occur in any of the patients.

Cerebrospinal fluid acetylcholinesterase and choline measurements in Huntington's disease

The caudate nucleus has the highest acetylcholinesterase (AChE) activity in the brain and it has been shown that autopsied brain tissue of patients with Huntington's disease (HD) have reduced levels of acetylcholine. Because of these findings, the cholinergic function in HD was studied by measuring cerebrospinal fluid (CSF) choline levels and AChE activity during a randomized, double-blind, cross-over, placebo-controlled clinical trial of isoniazid. While mean choline levels adjusted for age were lower compared with controls (P = 0.0007), AChE activity did not differ between HD patients and normal controls. Treatment with isoniazid had no significant effect on CSF choline levels or CSF AChE activity. CSF AChE activity showed a statistically significant increase with advancing age. The reduced level of choline in CSF of HD patients may reflect either a defect in choline transport into the brain or a decrease of choline-phospholipid output from the brain.

Levels of cerebrospinal fluid acetylcholinesterase in tuberculous and pyogenic meningitis in children

Levels of cerebrospinal fluid acetylcholinesterase in tuberculous and pyogenic meningitis in children

CSF choline and acetylcholinesterase in early-onset vs. late-onset Alzheimer's disease patients.

Cerebrospinal fluid acetylcholinesterase (AChE) activity levels and choline (Ch) levels were studied in 52 dementia of Alzheimer type (DAT) patients and 20 age-matched controls. The AChE activity was significantly lower and Ch levels were significantly higher in DAT patients than the age-matched controls. There was no significant difference in AChE activity and Ch levels between early-onset (less than or equal to 65 years) patients and late-onset (greater than 65 years) patients. However, the AChE activity was significantly lower in early-onset patients compared with their age-matched controls but no difference was observed in late-onset patients compared with their age-matched controls. None of the biological measures (AChE, Ch) were significantly correlated with the degree of cognitive impairment, duration of the illness or the sex of these patients.

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.

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.

Cerebrospinal fluid neurochemistry in the myoclonic subtype of Alzheimer's disease

Monoamine metabolites, biopterin, acetylcholinesterase (AChE) activity, and somatostatin-like immunoreactivity (SLI) were determined in the lumbar cerebrospinal fluid (CSF) of 24 patients with dementia of the Alzheimer type (DAT) without myoclonus or extrapyramidal signs, in 8 patients with DAT and myoclonus, and in 14 age-matched healthy control subjects. In patients with DAT with myoclonus as compared with both DAT patients without myoclonus and control subjects, the concentrations of homovanillic acid and biopterin were significantly decreased. 5-Hydroxyindoleacetic acid was significantly lower in patients with myoclonic DAT as compared to patients with nonmyoclonic DAT, but not significantly lower than in control subjects. CSF AChE and SLI were significantly reduced in patients with DAT with or without myoclonus, as compared with control subjects, but AChE and SLI were not significantly different between dementia groups. These results suggest that DAT patients with myoclonus represent a distinct clinical and neurochemical DAT subtype.

No effect of haloperidol on cerebrospinal fluid acetylcholinesterase in patients with schizophrenia

No effect of haloperidol on cerebrospinal fluid acetylcholinesterase in patients with schizophrenia

Cerebrospinal fluid cholinesterases in aging and in dementia of the Alzheimer type.

Protein concentration and acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities were assayed in the cerebrospinal fluid (CSF) of 26 healthy normal subjects (20-86 years old), 27 patients with dementia of the Alzheimer type (DAT), and 10 patients with dementia of the Alzheimer type with extrapyramidal signs (EDAT). In normal subjects, there was an age-related increase in CSF protein and AChE activity and a significant correlation (p less than 0.001) between CSF protein and BChE activity. In the DAT and EDAT groups, CSF AChE activities (mean +/- SD = 17.5 +/- 3.6 and 15.3 +/- 4.4 nmol/min/ml, respectively) were significantly lower (p less than 0.05) than in 13 age-matched control subjects (21.5 +/- 5.6 nmol/min/ml). In contrast, neither CSF protein concentration, BChE activity, nor the ratio of AChE/BChE differed significantly between groups. In patients with DAT, CSF AChE activity was significantly lower (p less than 0.05) in subjects with an early onset compared to those with a late onset (16.4 +/- 3.4 and 19.7 +/- 2.8 nmol/min/ml, respectively), and activity in the latter group did not differ significantly from control values. CSF AChE activity was not related to dementia severity and did not change significantly over an 18-month period. Although these results confirm a cholinergic deficit in patients with DAT, the considerable overlap of CSF AChE activity between groups and the nonsignificant correlation between AChE activity and dementia severity limit the usefulness of CSF AChE as a diagnostic marker of this disorder.

Increased monoamine metabolite concentrations and cholinesterase activities in cerebrospinal fluid of patients with acute stroke.

Twenty-one patients with acute brain infarction, 8 with transient ischemic attack and 20 controls were investigated for lumbar cerebrospinal fluid (CSF) monoamine metabolites and cholinesterases. The diseased patients were lumbar punctured on 2 occasions, mean Days 1 (0-3) and 5 (3-9) after debut of symptoms. Monoamine concentrations were determined by reverse phase liquid chromatography with electrochemical detection and the cholinergic enzymes were measured photometrically. Increased concentrations of 3-methoxytyramine (3-MT), homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HI-AA) and increased activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in lumbar cerebrospinal fluid was found in patients with acute brain infarction when compared to control values, while the levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) were not altered. No change of any neurotransmitter metabolite concentration/enzyme activity were found between Day 1 and Day 5 in the diseased patients. These data suggest an increased release of these neurotransmitter markers from necrotic brain areas into the cerebrospinal fluid and/or altered barriers between blood, brain and CSF and/or a dysfunction of the arachnoid villi to clear substances from the CSF. We therefore concluded that CSF neurotransmitters may be useful as specific brain markers in acute stroke.

Molecular forms of acetylcholinesterase and butyrylcholinesterase in human plasma and cerebrospinal fluid.

The measurement of cholinesterase activities in either plasma or cerebrospinal fluid (CSF) may ultimately prove to be relevant in the diagnosis of neurological and neuropsychiatric disorders. However, studies to date have examined only total enzyme activities. Therefore in the present study we have examined the distribution of the individual molecular forms of both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in plasma and CSF using sucrose density gradient centrifugation. Although the total activities of AChE were of the same order of magnitude in plasma and CSF, there was a considerable difference (120-500-fold) between total BChE activity in the CSF and the BChE-rich plasma. The analysis of the individual molecular forms revealed that the predominant molecular species of AChE and BChE in the CSF--both lumbar and ventricular--was the G4 form. The G4 form also constituted the majority of the plasma BChE activity and, on average, over half (56%) of the plasma AChE activity. The significance of the AChE and BChE molecular form compositions of both plasma and CSF and their possible relationship to pathological states are discussed.

Acetylcholinesterase and butyrylcholinesterase activity in the cerebrospinal fluid of patients with neurodegenerative diseases involving cholinergic systems.

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were assayed in the cerebrospinal fluid (CSF) of subjects with neurodegenerative diseases (dementing and non-dementing, with and without known cholinergic lesions), to determine whether CSF AChE is a valid marker of central cholinergic activity. The relative proportions of the different forms of each enzyme and of AChE to BChE were similar in CSF and brain. AChE decreased in Huntington's chorea (degeneration of striatal cholinergic interneurons) but also in multiple sclerosis (not known to affect cholinergic systems). BChE paralleled AChE, although the enzymes were dissociated in some patients. It is concluded that CSF AChE activity may globally reflect brain AChE, but pathology-induced changes may not be directly reflected.

Cholinesterases in cerebrospinal fluid. A longitudinal study in Alzheimer disease.

We measured acetylcholinesterase (AChE) and butyrylcholinesterase activities in the lumbar cerebrospinal fluid (CSF) of 39 patients with dementia of Alzheimer type and 21 age-matched controls. The mean lumbar CSF AChE activity in our patients did not differ significantly from that of controls. The 7S and 11S molecular forms were also unchanged. When CSF was analyzed at six-month intervals, there was no significant decline in AChE activity over a span of 12 months. Our results and those of previous studies demonstrate that CSF AChE is not a useful diagnostic marker of Alzheimer disease.

Cerebrospinal fluid levels of angiotensin- converting enzyme, acetylcholinesterase, and dopamine metabolites in dementia associated with Alzheimer's disease and Parkinson's disease: A correlative study

Mean levels of the two hydrolases angiotensin-converting enzyme (ACE) and acetylcholinesterase (AChE), the dopamine metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and total protein concentration were examined in cerebrospinal fluid (CSF) samples from a group of patients with dementia of the Alzheimer's type, a group of comparably demented patients with Parkinson s disease, and a neurologically healthy elderly control group. Both pathological groups exhibited a significant decrease in the mean levels of ACE activity and DOPAC per milliliter and were distinguishable from one another based on mean CSH HVA levels. Unlike the Parkinson's disease group, whose mean concentration of HVA was lower than, but not significantly different from, that of the control group, the mean HVA concentration of the Alzheimer's disease group was significantly elevated. In contrast, comparisons of the mean CSF AChE activity (expressed per milliliter or per milligram of protein) and CSF total protein concentration did not reveal significant differences for any of the groups. Independent of CSF protein concentration, ACE activity per milliliter exhibited a positive correlation with AChE activity per milliliter within the control and Parkinson's disease groups, whereas a statistically significant correlation for these CSF hydrolases was not observed within the Alzheimer's disease group. Thus, the CSF profiles for patients with mild dementias associated with Alzheimer's or Parkinson's disease differed by at least two neurochemical criteria. Based on the levels of ACE activity, DOPAC, and HVA per milliliter of CSF, two discriminant functions were derived and resulted in the correct classification of 71% of all subjects ( n = 38) into Alzheimer's disease, Parkinson's disease, and neurologically healthy control groups.

The effects of physostigmine on acetylcholinesterase activity of CSF, plasma and brain. A comparison of intravenous and intra ventricular administration in beagle dogs

The effects of various doses of physostigmine (Phy) on the activity of acetylcholinesterase (AChE) in plasma, cerebrospinal fluid (CSF) and brain were studied in beagle dogs. Two routes of administration were compared: intravenous (i.v.) and intracerebroventricular (i.c.v.). With intracerebroventricular administration, over 90% inhibition of the activity of AChE in CSF was reached within 5min of injection at all doses (10–120μg). Even at the smallest dose (10 μg), 50% inhibition of activity of the enzyme in CSF was still present at 90 min. The activity of AChE in plasma was only minimally inhibited by intraventricular administration of physostigmine. A different response was obtained following intravenous administration of physostigmine (250–1000 μg). The activity of AChE in plasma was inhibited but the activity of AChE in CSF was increased (36–80% at 180 min). This increase was dose-dependent and was blocked by pretreatment with atropine (1.5mg i.v.) which suggests the involvement of a muscarinic receptor mechanism. The time course of the accumulation and regional distribution of [ 3H]physostigmine in brain also varied with the route of administration. At 5 min, with intravenous administration, physostigmine (1000 μg) reached greater concentrations and caused greater inhibition of AChE in the cortex. With intraventricular administration, physostigmine (80 μg) reached greater concentrations in two regions adjacent to the ventricular surface: the striatum and hippocampus. These regions also showed greater inhibition of the activity of AChE. Moderate to severe symptoms of cholinergic hyperactivity were seen only with the largest intraventricular dose (120 μg). This study suggests that intraventricular administration of physostigmine, a reversible inhibitor of cholinesterase (ChE), may offer distinct advantages over intravenous administration. Inhibition of acetylcholinesterase in CSF was more pronounced and persisted longer when physostigmine was administered directly into the CSF than when given intravenously. The implications of this study for a cholinergic therapy of Alzheimer's disease are discussed.

Acetylcholinesterase activity in cerebrospinal fluid of patients with Alzheimer's disease and senile dementia

Acetylcholinesterase (AChE) in the cerebrospinal fluid (CSF) from patients with Alzheimer-type dementia and control subjects was analyzed by centrifugation on a sucrose density gradient, and by column chromatography on Sephadex G-200. The sedimentation coefficient and molecular weight of CSF AChE were calculated as 10S and 380 000, respectively, which corresponded to those of G4 isozyme in the brain. Other isozymes of AChE were not detected in the CSF of either patients with Alzheimer-type dementia or the controls. Sufficient activity of AChE was observed in the CSF of a patient with familial pseudocholinesterase deficiency, although the pseudocholinesterase activity was not found either in the serum or in the CSF. CSF AChE activity in control subjects increased with advancing age ( P < 0.02). AChE activity in the CSF was significantly lower in patients with presenile dementia (Alzheimer's disease), compared with age-matched control subjects ( P < 0.001). However, AChE activity in the CSF showed a wide variation among patients of Alzheimer-type dementia with a late onset (senile dementia).

6-Hydroxydopamine-induced turning behaviour in the rat: The significance of acetylcholinesterase in cerebrospinal fluid

In the substantia nigra, acetylcholinesterase may have a novel function related not to cholinergic transmission, but to the homeostasis of dopaminergic nigrostriatal neurones. The initial aim of this study was thus to see whether, in the rat, release of the enzyme into cerebrospinal fluid would reflect turning behaviour following unilateral 6-hydroxydopamine lesions of varying severity. It was found that acetylcholinesterase levels, lower than those in the cerebrospinal fluid of control rats, were accompanied by marginal circling behaviour and a small loss of striatal dopamine: on the other hand, elevated acetyl-cholinesterase activity was observed in the cerebrospinal fluid of rats displaying vigorous turning behaviour and with large depletion of striatal dopamine. It has already been demonstrated that exogenous acetylcholinesterase, applied locally to nigral neurones, has both electrophysiological and behavioural effects reminiscent of dopamine agonists. Hence it is possible that exogenous acetylcholinesterase could modify turning behaviour resulting from unilateral striatal dopamine depletion. Purified acetylcholinesterase, administered by cisternal puncture, attenuated circling behaviour for up to 7 days. The possible mechanisms are discussed by which endogenous acetylcholinesterase in cerebrospinal fluid could serve as an index of dopamine depletion in the nigrostriatal pathway and how exogenous enzymes might alleviate the accompanying motor dysfunction.

A semi-automated fluorimetric method for measuring acetylcholinesterase activity in small volumes of cerebrospinal fluid and tissue extracts using acetylcholine as substrate

A fluorimetric method for the assay of acetylcholinesterase (AChE; EC 3.1.1.7) in tissue extracts and cerebrospinal fluid, using acetylcholine as the substrate, is described. The method is based on the measurement of hydrogen peroxide, formed by the oxidation of choline resulting from the action of AChE on acetylcholine, by means of horseradish peroxidase and 4-hydroxy-3-methoxyphenylacetic acid (HVA) to yield a fluorescent derivative. Choline, if present in any sample to be analysed, is first removed by a modification of the peroxidase reaction during preincubation.

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.

Cerebral ventricular size and cerebrospinal fluid acetylcholinesterase levels in senile dementia of the Alzheimer type

Computed tomography (CT) was performed in 16 patients with a diagnosis of senile dementia of the Alzheimer type (SDAT). CT scans were rated without knowledge of clinical and laboratory data, and lateral ventricle-brain ratios (VBRs) calculated. Cerebrospinal fluid (CSF) acetylcholinesterase (AChE) activity was measured by radioenzymatic assay in all patients, and degree of dementia quantified using the Mini-Mental State Examination (MMSE). There were significant correlations between cerebral atrophy as assessed by VBR and CSF AChE activity. Cognitive impairment on MMSE also correlated significantly with VBR. These correlations were not accounted for by age, dilutional effects, or duration of illness. The relationship between VBR and AChE activity demonstrates an association between two independently determined pre-mortem measures of illness.