Cerebrospinal Fluid Acetylcholinesterase Research Articles

Phenotypic Displays of Cholinergic Enzymes Associate With Markers of Inflammation, Neurofibrillary Tangles, and Neurodegeneration in Pre- and Early Symptomatic Dementia Subjects

BackgroundCholinergic drugs are the most commonly used drugs for the treatment of Alzheimer’s disease (AD). Therefore, a better understanding of the cholinergic system and its relation to both AD-related biomarkers and cognitive functions is of high importance.ObjectivesTo evaluate the relationships of cerebrospinal fluid (CSF) cholinergic enzymes with markers of amyloidosis, neurodegeneration, neurofibrillary tangles, inflammation and performance on verbal episodic memory in a memory clinic cohort.MethodsIn this cross-sectional study, 46 cholinergic drug-free subjects (median age = 71, 54% female, median MMSE = 28) were recruited from an Icelandic memory clinic cohort targeting early stages of cognitive impairment. Enzyme activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) was measured in CSF as well as levels of amyloid-β1–42 (Aβ42), phosphorylated tau (P-tau), total-tau (T-tau), neurofilament light (NFL), YKL-40, S100 calcium-binding protein B (S100B), and glial fibrillary acidic protein (GFAP). Verbal episodic memory was assessed with the Rey Auditory Verbal Learning (RAVLT) and Story tests.ResultsNo significant relationships were found between CSF Aβ42 levels and AChE or BuChE activity (p > 0.05). In contrast, T-tau (r = 0.46, p = 0.001) and P-tau (r = 0.45, p = 0.002) levels correlated significantly with AChE activity. Although neurodegeneration markers T-tau and NFL did correlate with each other (r = 0.59, p < 0.001), NFL did not correlate with AChE (r = 0.25, p = 0.09) or BuChE (r = 0.27, p = 0.06). Inflammation markers S100B and YKL-40 both correlated significantly with AChE (S100B: r = 0.43, p = 0.003; YKL-40: r = 0.32, p = 0.03) and BuChE (S100B: r = 0.47, p < 0.001; YKL-40: r = 0.38, p = 0.009) activity. A weak correlation was detected between AChE activity and the composite score reflecting verbal episodic memory (r = −0.34, p = 0.02). LASSO regression analyses with a stability approach were performed for the selection of a set of measures best predicting cholinergic activity and verbal episodic memory score. S100B was the predictor with the highest model selection frequency for both AChE (68%) and BuChE (73%) activity. Age (91%) was the most reliable predictor for verbal episodic memory, with selection frequency of both cholinergic enzymes below 10%.ConclusionsResults indicate a relationship between higher activity of the ACh-degrading cholinergic enzymes with increased neurodegeneration, neurofibrillary tangles and inflammation in the stages of pre- and early symptomatic dementia, independent of CSF Aβ42 levels.

Cerebrospinal fluid cholinergic biomarkers are associated with postoperative delirium in elderly patients undergoing Total hip/knee replacement: a prospective cohort study

BackgroundPostoperative delirium (POD) is a frequent complication after surgery and its occurrence is associated with poor outcomes. The neuropathology of this complication is unclear, but it is important to evaluate relevant biomarkers for postoperative status. The purpose of this study is to explore the relationship between expression levels of cholinergic biomarkers in cerebrospinal fluid (CSF) and the occurrence and development of POD in elderly patients.MethodsFour hundred and ninety-two elderly patients aged 65 years old or older with elective total hip/knee replacement received combined spinal-epidural anesthesia. Preoperative baseline cognitive function was assessed using the Mini-Mental State Examination (MMSE) before surgery. Each patient was interviewed in post-anesthesia care unit (PACU) and on the first, second, third and seventh (or before discharge) postoperative days. POD was diagnosed using the Confusion Assessment Method (CAM), and POD severity was measured using the Memorial Delirium Assessment Scale (MDAS). Preoperative CSF and plasma choline acetyltransferase (ChAT), acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels were determined by ELISA. The levels of ChAT, AChE and BuChE activities were determined by spectrophotometry.ResultsPOD was detected in 11.4% (51/447) of the patients. AChE, BuChE, ChAT, TNF-α and IL-6 concentrations in CSF and plasma have higher consistency. In preoperative CSF and preoperative and postoperative plasma, down-regulation of the concentration and activity of AChE and BuChE as well as up-regulation of the concentration and activity of ChAT and the concentrations of IL-6 and TNF-α were observed in patients who developed POD, and the decrease in BuChE was the most obvious. Logistic analysis showed the activities of ChAT, AChE and BuChE in CSF were still related to POD after adjusting for related factors such as sex, age, years of education, height, weight, body mass index (BMI), and American Society of Anesthesiologists (ASA) class. Receiver Operating Characteristic (ROC) curve analysis was conducted to determine the Area Under Curve (AUC) of AChE, BuChE and ChAT activity in CSF was 0.679 (P < 0.01), 0.940 (P < 0.01) and 0.819 (P < 0.01) respectively and found that BuChE activity had the most accurate diagnostic value.ConclusionThe changes in preoperative activity of AChE, BuChE and ChAT in CSF were associated with the development of POD in elderly patients, and BuChE activity had the greatest diagnostic value, which may be related to central cholinergic degradation. These cholinergic biomarkers might participate in the neuropathology of POD, pending further investigations.Trial registrationThis study was registered at Chictr.org.cn (NO. ChiCTR1900023729) June 9th, 2019. (Retrospectively registered).

CSF Cholinergic Index, a New Biomeasure of Treatment Effect in Patients With Alzheimer's Disease.

Alzheimer’s disease (AD) is a progressive disease with early degeneration of the central cholinergic neurons. Currently, three of four AD drugs act by inhibiting the acetylcholine (ACh) degrading enzyme, acetylcholinesterase (AChE). Efficacy of these drugs depends on available amount of ACh, which is biosynthesized by choline acetyltransferase (ChAT). We investigated whether treatment with a cholinesterase-inhibitor, galantamine, alters the relative levels of AChE to ChAT in cerebrospinal fluid (CSF) and whether levels of these CSF biomarkers correlate with in vivo AChE activity and nicotinic binding sites in the brain assessed by positron emission tomography (PET). Protein concentrations and activities of ChAT and AChE were measured in CSF of 18 patients with mild AD prior to and after 3 months of treatment with galantamine (n = 12) or placebo (n = 6), followed by nine additional months of galantamine treatment in all patients. A Cholinergic index was defined as the ratio of ChAT to AChE in CSF and was evaluated in relation to the in vivo AChE activity, the nicotinic binding sites and different measures of cognition. Besides an expected inhibition of AChE activity, galantamine treatment was accompanied by a mild increase in CSF ChAT activity. Thereby, the Cholinergic index was significantly increased in the Galantamine group (60% ± 14) after 3 months compared to baseline (p < 0.0023) or (p < 0.0004). This index remained high in the Galantamine group compared to baseline (54% ± 11) at 12 months follow-up, while it showed an increase in the Placebo group when they switched to active galantamine treatment (44% ± 14 vs. baseline, 61% ± 14 vs. 3 months, all p-values < 0.05). Furthermore, the in vivo brain AChE activity (assessed by PET) correlated with the CSF Cholinergic index at 12 months (r = 0.98, p < 0.001). The CSF Cholinergic index also correlated with ADAS-Cog and some other neuropsychological tests at 12 months. This is the first study assessing a CSF Cholinergic index in relation to treatment with a cholinesterase inhibitor. The treatment-specific increase in CSF ChAT activity suggests that cholinesterase-inhibitors may also increase the ACh-biosynthesis capacity in the patients. Additional studies are warranted to evaluate the utility of the CSF Cholinergic index as a biomeasure of therapeutic effect in AD.

Studying of Oxidative Stress and Activity of Some Enzymes in Cerebrospinal Fluid from Children with Hydrocephalus Disease

This research include studying the oxidative stress state and the activity of some enzymes in the cerebrospinal fluid (CSF) from children with hydrocephalus by the determination of (15) Biochemical parameters which include: Acetylcholinesterase (AChE), Pseudocholinesterase (PChE), Monoamin oxidase A (MAOA), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), Creatinine kinase (CK), Lactate dehydrogenase (LDH), Superoxide dismutase (SOD), Uric acid (UA), Vitamin D, Total protein (Tp), Albumin (Alb), Ceruloplasmin (Cp), Malonadialdehyde (MDA), The study was done on (176) child with hydrocephalus (110) were male , (66) female and (67) healthy child as control group (39) were male and (28) female ,the age of children with hydrocephalus and control group ranged from 1-14 month for both sexes. The results showed that there was a significant increase in the activity of AChE, PChE, MAOA, AST, ALT, ALP, CK and LDH in CSF for children with hydrocephalus compared with healthy group for both sexes, these result were indicated that these parameters may be good biochemical markers for this disease . Beside of that, the results showed there was a highly oxidative stress in the patients for both sexes, so there was a significant increase in the activity of SOD, Tp, Alb and oxidant indicator of MDA, with a significant decrease in vit. D, uric acid and Cp levels in CSF patients compared with healthy group for both sexes,

Cholinesterase Inhibitor Therapy in Alzheimer's Disease: The Limits and Tolerability of Irreversible CNS-Selective Acetylcholinesterase Inhibition in Primates.

Irreversible acetylcholinesterase (AChE) inhibition accumulates to high levels in the central nervous system (CNS) because AChE turnover in the brain is much slower than in peripheral tissues. As expected from this CNS selectivity, the irreversible AChE inhibitor methanesulfonyl fluoride (MSF) produces significant cognitive improvement in Alzheimer's disease patients without the gastrointestinal toxicity that plagues other AChE inhibitors. However, without dose-limiting gastrointestinal toxicity, one shortcoming of the prior human studies of MSF is that the upper limits of CNS AChE inhibition that might be tolerated could not be tested. Therefore, in this study, monkeys were treated with escalating intramuscular (IM) doses of MSF that culminated with several weeks of 1.5 mg/kg dosing, more than eight times the prior human clinical dose, still without signs of toxicity. Brain biopsies showed that ∼80% AChE inhibition had been produced and that the new synthesis of cortical AChE had a half-time (t1/2) of ∼12 days. A single IM dose of 1.5 mg/kg MSF produced ∼59% inhibition in cerebrospinal fluid (CSF) AChE as measured one day later. This corresponds to a peak of ∼80% inhibition in CSF AChE at the time of the injection, recovering with a t1/2 of 2.4 days. Computational analyses suggest that MSF at clinically relevant doses could theoretically produce a steady-state AChE inhibition between 65% and 85% in the CNS. These data suggest that the full therapeutic advantage of AChE inhibition therapy can be realized without interference from dose-limiting gastrointestinal toxicity if an irreversible inhibitor is employed.

Cognitive Dysfunction and its Determinants in Patients with Neurocysticercosis.

Introduction:Neurocysticercosis (NCC) is the most common parasitic infection of man. In addition to a headache, seizures, and focal deficits, this is associated with significant cognitive dysfunction. Many studies revealed that the number and location of lesions are not always responsible for cognitive dysfunction. Cholinesterase and pseudocholinesterase are found in the walls of the cysticercus which could contribute to cholinergic depletion and thus cognitive dysfunction.Patients and Methods:A total of 43 patients who presented with NCC were evaluated for cognitive deficits, as well as cholinesterase levels in cerebrospinal fluid (CSF) with control CSF from patients undergoing spinal anesthesia. Blood levels of interleukin-10 and tumor necrosis factor alpha were also estimated and correlated with cognitive deficits.Results:There is a mild increase in the acetylcholinesterase in CSF of patients compared to controls, but it did not correlate with cognitive deficits. There is an increase in interleukins to a significant level which correlates with vesicular stage of the organism and cognitive impairment. The number of lesions also correlated with cognitive impairment even though the location did not. The domains of cognitive deficits seen are sustained attention, category fluency, verbal working memory, planning, set shifting, verbal learning, visual memory, and construction.Discussion and Conclusion:NCC is associated with multi-domain cognitive impairment correlates with vescicular stage, proinflammatory cytokines and number of lesions but not location, vesicular stage, and proinflammatory cytokines.

Cerebrospinal Fluid (CSF) 25-Hydroxyvitamin D Concentration and CSF Acetylcholinesterase Activity Are Reduced in Patients with Alzheimer's Disease

BackgroundLittle is known of vitamin D concentration in cerebrospinal fluid (CSF) in Alzheimer´s disease (AD) and its relation with CSF acetylcholinesterase (AChE) activity, a marker of cholinergic function.MethodsA cross-sectional study of 52 consecutive patients under primary evaluation of cognitive impairment and 17 healthy controls. The patients had AD dementia or mild cognitive impairment (MCI) diagnosed with AD dementia upon follow-up (n = 28), other dementias (n = 12), and stable MCI (SMCI, n = 12). We determined serum and CSF concentrations of calcium, parathyroid hormone (PTH), 25-hydroxyvitamin D (25OHD), and CSF activities of AChE and butyrylcholinesterase (BuChE). FindingsCSF 25OHD level was reduced in AD patients (P < 0.05), and CSF AChE activity was decreased both in patients with AD (P < 0.05) and other dementias (P < 0.01) compared to healthy controls. None of the measured variables differed between BuChE K-variant genotypes whereas the participants that were homozygous in terms of the apolipoprotein E (APOE) ε4 allele had decreased CSF AChE activity compared to subjects lacking the APOE ε4 allele (P = 0.01). In AD patients (n=28), CSF AChE activity correlated positively with CSF levels of total tau (T-tau) (r = 0.44, P < 0.05) and phosphorylated tau protein (P-tau) (r = 0.50, P < 0.01), but CSF activities of AChE or BuChE did not correlate with serum or CSF levels of 25OHD.ConclusionsIn this pilot study, both CSF 25OHD level and CSF AChE activity were reduced in AD patients. However, the lack of correlations between 25OHD levels and CSF activities of AChE or BuChE might suggest different mechanisms of action, which could have implications for treatment trials.

Acetylcholinesterase activity in the cerebrospinal fluid of dogs with seizures

Recent studies in animal models have focused on the role of cholinergic elements, mainly acetylcholinesterase (AChE) and the ‘readthrough’ acetylcholinesterase isoform (AChE-R), in seizures. A prospective double-masked study was conducted to assess the activity of AChE and AChE-R in cerebrospinal fluid (CSF) of 26 dogs post-seizure, 28 dogs with intervertebral disc disease (IVDD) and 16 healthy dogs. AChE was also measured in the serum in the post-seizure and IVDD groups. The results showed no significant differences in CSF AChE among the three groups. AChE-R was not detected in any dog and AChE in the serum was similar between groups. This preliminary study provides new information on AChE and AChE-R in the CSF and sera of dogs following naturally-occurring seizures.

A Highly Sensitive Gold‐Nanoparticle‐Based Assay for Acetylcholinesterase in Cerebrospinal Fluid of Transgenic Mice with Alzheimer's Disease

A highly sensitive, selective, and dual-readout (colorimetric and fluorometric) assay for acetylcholinesterase (AChE) based on Rhodamine B-modified gold nanoparticle is reported. Due to its good sensitivity and selectivity, the assay can be used for monitoring AChE levels in the cerebrospinal fluid of transgenic mice with Alzheimer's disease.

Changes in CSF acetyl- and butyrylcholinesterase activity after long-term treatment with AChE inhibitors in Alzheimer’s disease

To measure cerebrospinal fluid (CSF) activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in patients with Alzheimer's disease (AD) participating in randomized clinical trials from three European centers, before and after long-term treatment with different AChE inhibitors (AChEIs). Of the 144 patients included in the study, 104 were treated with donepezil, 15 with galantamine, 16 with rivastigmine, and nine with placebo. CSF AChE and BChE activities were measured at baseline and after 1- year treatment. Donepezil and galantamine groups showed a significant increase in CSF AChE activity at follow-up, while no changes for BChE activity were observed; in donepezil group, a positive correlation between plasma concentration and AChE activity was documented. Conversely, in rivastigmine group, a decrease in CSF activity of both enzymes was observed. CSF AChE and BChE activities were not correlated with the clinical outcome in any group considered. CSF biomarkers did not show any change after treatment. AChEIs differently influence the activity of target enzymes in CSF independent of their pharmacodynamic effects.

Effects of Cholinesterase Inhibitors on the Activities and Protein Levels of Cholinesterases in the Cerebrospinal Fluid of Patients with Alzheimers 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.

Different Cholinesterase Inhibitor Effects on CSF Cholinesterases in Alzheimer Patients

The current study aimed to compare the effects of different cholinesterase inhibitors on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities and protein levels, in the cerebrospinal fluid (CSF) of Alzheimer disease (AD) patients. AD patients aged 50-85 years were randomized to open-label treatment with oral rivastigmine, donepezil or galantamine for 13 weeks. AChE and BuChE activities were assayed by Ellman's colorimetric method. Protein levels were assessed by enzyme-linked immunosorbent assay (ELISA). Primary analyses were based on the Completer population (randomized patients who completed Week 13 assessments). 63 patients were randomized to treatment. Rivastigmine was associated with decreased AChE activity by 42.6% and decreased AChE protein levels by 9.3%, and decreased BuChE activity by 45.6% and decreased BuChE protein levels by 21.8%. Galantamine decreased AChE activity by 2.1% and BuChE activity by 0.5%, but increased AChE protein levels by 51.2% and BuChE protein levels by 10.5%. Donepezil increased AChE and BuChE activities by 11.8% and 2.8%, respectively. Donepezil caused a 215.2% increase in AChE and 0.4% increase in BuChE protein levels. Changes in mean AChE-Readthrough/Synaptic ratios, which might reflect underlying neurodegenerative processes, were 1.4, 0.6, and 0.4 for rivastigmine, donepezil and galantamine, respectively. The findings suggest pharmacologically-induced differences between rivastigmine, donepezil and galantamine. Rivastigmine provides sustained inhibition of AChE and BuChE, while donepezil and galantamine do not inhibit BuChE and are associated with increases in CSF AChE protein levels. The clinical implications require evaluation.

Amyloid beta protein precursors with kunitz-type inhibitor domains and acetylcholinesterase in cerebrospinal fluid from patients with dementia of the Alzheimer type.

We used the ELISA to measure the concentration of amyloid protein precursor with Kunitz type trypsin inhibitor domains (APPI) in CSF of dementia of the Alzheimer type (DAT) and examined the correlation of APPI with acetylcholinesterase (AChE) and somatostatin (SRIF). We found the APPI concentration in CSF of DAT to be significantly elevated compared with that of multi-infarct dementia and controls. We could significantly correlate APPI with AChE, but not correlate APPI with SRIF. The present results suggest that measurement of CSF APPI levels may be useful for diagnosis of DAT and the change of APPI may closely be associated with abnormality of acetylcholine system in DAT that has been reported.

Association between acetylcholinesterase and β-amyloid peptide in Alzheimer's cerebrospinal fluid

The altered expression of acetylcholinesterase (AChE) in the brains of patients with Alzheimer's disease (AD) has raised much interest of late. Despite an overall decrease in the AD brain, the activity of AChE increases around β-amyloid plaques and indeed, the β-amyloid peptide (Aβ) can influence AChE levels. Such evidence stimulated our interest in the possibility that the levels of AChE and amyloid might vary together in AD. We previously found that the different AChE forms present in both the brain and in the cerebrospinal fluid (CSF) of AD patients varied in conjunction with abnormal glycosylation. Thus, the alterations in glycosylation are correlated with the accumulation of a minor subspecies of AChE monomers. We also recently analysed whether long-term exposure to the cholinesterase inhibitor (ChE-I) donepezil influences the AChE species found in AD CSF. The marked increase in CSF-AChE activity in AD patients following long-term treatment with donepezil was not paralleled by a rise in this subset of light variants. Hence, the correlation with the levels of CSF-Aβ is unique to these AChE species in patients receiving such treatment. The aim of this report is to review the links between AChE and β-amyloid, and to discuss the significance of the responses of the distinct AChE species to ChE-I during the treatment of AD.

Phenomenological Distinctions Needed in DSM-V: Delirium, Subsyndromal Delirium, and Dementias

Phenomenological Distinctions Needed in DSM-V: Delirium, Subsyndromal Delirium, and Dementias

Cerebrospinal fluid acetylcholinesterase changes after treatment with donepezil in patients with Alzheimer’s disease

We analyzed whether donepezil differently influences acetylcholinesterase (AChE) variants from cerebrospinal fluid (CSF) in patients with Alzheimer's disease (AD) after long-term treatment. Overall CSF-AChE activity in AD patients before treatment was not different from controls, but the ratio between the major tetrameric form, G(4), and the smaller G(1) and G(2) species was significantly lower. AChE levels at study outset were found to correlate positively with beta-amyloid (1-42) (Abeta42). When patients were re-examined after 12 months treatment with donepezil, there was a remarkable increase in both the G(4) and the lighter species of CSF AChE. As compared with placebo, donepezil caused decreases in the percentage of AChE that failed to bind to the lectin concanavalin A and the antibody AE1. These non-binding species comprised primarily a small subset of G(1) and G(2) forms. In treated patients, these light variants were the only subset of CSF AChE that correlated with CSF-Abeta42 levels. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis showed that a 77-kDa band, attributed in part to inactive AChE, was lower in AD patients than in controls. Unlike enzyme activity, the intensity of this band did not increase after donepezil treatment. The varying responses of different AChE species to ChE-I treatment suggest different modes of regulation, which may have therapeutic implications.

Decreased Cerebrospinal Fluid Acetylcholinesterase in Patients with Subcortical Ischemic Vascular Dementia

The main objective was to investigate the acetylcholinesterase E (AChE) activity in the cerebrospinal fluid (CSF) of patients with three common dementia disorders. We also wanted to investigate the influence of apolipoprotein E (ApoE) Ε4 allele possession and CSF-τ level on the CSF-AChE activity in these patients. The study included 17 consecutive patients with subcortical vascular dementia (SVD), 39 with Alzheimer’s disease (AD), 14 with frontotemporal dementia (FTD) and 12 controls. CSF was obtained by lumbar puncture and CSF-AChE activity was measured by an enzyme antigen immunoassay. CSF-AchE activity was significantly decreased compared to controls only in the SVD group (p = 0.010). The CSF-τ level was increased in the AD group compared to the control (p < 0.01) and FTD groups (p < 0.05). No influence of ApoE Ε4 allele possession on CSF-AChE activity was found. It is suggested that abnormal CSF-AChE activity in patients with SVD reflects a disturbance in the cholinergic system.

Changes in molecular isoform distribution of acetylcholinesterase in rat cortex and cerebrospinal fluid after intracerebroventricular administration of amyloid β-peptide

Previous studies have shown that an abnormal salt-soluble form of G 1 acetylcholinesterase (AChE) is increased in the Alzheimer's disease (AD) brain. The aim of the present study was to examine changes in AChE activity in an in vivo model of β-amyloid peptide (Aβ) administration. Rats received intracerebroventricular injections of Aβ 25–35 (20 μg/day for seven days). Levels of AChE were measured in cerebral cortex and cerebrospinal fluid (CSF) after two months. Aβ 25–35 administration did not alter total AChE activity in the cerebral cortex or CSF. However, analysis of salt-extractable AChE isoforms revealed an increase in the proportion of G 1 in both cortex and CSF, similar to that previously observed in AD patients. The results support the view that changes in AChE isoform pattern in the AD brain are a direct consequence of Aβ accumulation.

Cerebrospinal fluid acetylcholinesterase activity after long-term treatment with donepezil and rivastigmina

At present acetylcholinesterase (AChE) inhibitors (AChEIs) represent the only reliable therapeutic resource for symptomatic treatment of Alzheimer Disease (AD). This study was designed to assess the effects of 6–12 month treatment with AChEIs donepezil and rivastigmine on cerebrospinal fluid (CSF) AChE and butyrylcholinesterase (BuChE) activity in AD patients. The pattern of AChE isoforms (G4, G1, G2) before and after treatment was investigated as well. In AD patients treated with donepezil a significant increase of CFS AChE activity was observed, whereas treatment with rivastigmine induced a significant decrease of AChE activity. Both drugs did not change BuChE activity and tended to restore the physiological pattern of AChE isoform. The possible significance of the influence of AChEIs on CSF AChE activity and isoforms is discussed.

Differential increase in cerebrospinal fluid-acetylcholinesterase after treatment with acetylcholinesterase inhibitors in patients with Alzheimer's disease

The clinical significance and the effects of pharmacological treatment of patients with Alzheimer's disease (AD) were evaluated by measurement of acetylcholinesterase (AChE) in the cerebrospinal fluid (CSF). CSF–AChE of AD patients was lower, not significantly, compared with controls. However, CSF–AChE was significantly increased after treatment of AD patients with AChE inhibitors (donepezil and galantamine). The increase was higher in patients treated with donezepil than in those treated with galantamine, which might be related to different mechanisms for the substances. The increase was also dose-dependent, and was especially marked in patients showing a clinical response. These data suggest that CSF biomarkers are capable not only of identifying a biochemical effect of drugs, but also of differentiating between different compounds in a dose-dependent manner.