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- Darreh-Shori, T., et al.
(författare)
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Changes in the activity and protein levels of CSF acetylcholinesterases in relation to cognitive function of patients with mild Alzheimer's disease following chronic donepezil treatment
- 2006
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Ingår i: Journal of Neural Transmission. - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 113:11, s. 1791-1801
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. To evaluate long-term changes in acetylcholinesterase (AChE) activity in CSF and blood following donepezil treatment in relation to the concentration of donepezil and cognition in AD patients. Methods. CSF or blood (or both) samples of a total of 104 patients with mild AD were used [MMSE score 23 +/- 0.4; age 75 +/- 1 years (mean +/- SEM); n = 53 for CSF and n = 51 for plasma/red blood cell (RBC) samples]. The patients were treated with 5 or 10 mg/day donepezil and clinically followed for 2 years. The CSF and RBC AChE activities were measured by the Ellman's direct colorimetric assay. Protein levels of two variants of AChE ("read-through" AChE-R and synaptic AChE-S) were determined by an ELISA-like method. Results. The plasma donepezil concentration was dose-dependent (between 30 and 60 ng/mL in the 5-mg and 10-mg group, respectively). The CSF donepezil concentration was 10 times lower than the plasma level and showed dose- and time-dependent kinetics. The RBC AChE inhibition was moderate (19-29%). CSF AChE-S inhibition was estimated to 30-40% in the 5-mg and 45-55% in the 10-mg group. Positive correlations were observed between the CSF AChE inhibition, an increased protein level of the AChE-R variant and MMSE examination. Patients with high AChE inhibition (>= 45%) showed a stabilized MMSE test result after up to two years, while a significant decline was observed in AD patients with lower AChE inhibition (<= 30%). Conclusions. An increase in the protein level of the AChE-R variant corresponded to a high AChE inhibition in CSF and favored less cognitive deterioration.
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- Mattsson, Niklas, 1979, et al.
(författare)
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Age and diagnostic performance of Alzheimer disease CSF biomarkers.
- 2012
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Ingår i: Neurology. - : American Academy of Neurology (AAN). - 1526-632X .- 0028-3878. ; 78:7, s. 468-76
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Tidskriftsartikel (refereegranskat)abstract
- Core CSF changes in Alzheimer disease (AD) are decreased amyloid β(1-42), increased total tau, and increased phospho-tau, probably indicating amyloid plaque accumulation, axonal degeneration, and tangle pathology, respectively. These biomarkers identify AD already at the predementia stage, but their diagnostic performance might be affected by age-dependent increase of AD-type brain pathology in cognitively unaffected elderly.
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- Olsson, A, et al.
(författare)
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Measurement of alpha- and beta-secretase cleaved amyloid precursor protein in cerebrospinal fluid from Alzheimer patients
- 2003
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Ingår i: Experimental Neurology. - 0014-4886. ; 183, s. 74-
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Tidskriftsartikel (refereegranskat)abstract
- One of the major histopathological hallmarks of Alzheimer's disease (AD) is redundant senile plaques mainly composed of beta-amyloid (Abeta) aggregates. Alternative cleavage of the amyloid precursor protein (APP), occurring in both normal and AD subjects, results in the generation and secretion of soluble APP (sAPP) and Abeta. We examined the cerebrospinal fluid (CSF) for alpha- and beta-secretase cleaved sAPP (alpha-sAPP and beta-sAPP) in 81 sporadic AD patients, 19 patients with mild cognitive impairment, and 42 healthy controls by using newly developed sandwich enzyme-linked immunosorbent assay methods. We found that neither the level of CSF-alpha-sAPP nor CSF-beta-sAPP differed between sporadic AD patients and healthy controls. These findings further support the conclusion that there is no change in APP expression in sporadic AD. However, the level of CSF-beta-sAPP was significantly increased in patients with mild cognitive impairment compared to controls. We also investigated the relationship between the CSF level of alphabeta-sAPP and Abeta(42) and the apoE epsilon4 (apoFA.) allele. Significantly lower levels of CSF-alpha-sAPP were found in AD patients possessing one or two apoE4 alleles than in those not possessing the apoE4 allele. Neither the levels of CSF-beta-sAPP nor CSF-Abeta(42) differed when comparing ApoE4 allele-positive with allele-negative individuals. (C) 2003 Elsevier Science (USA). All rights reserved.
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- Parnetti, L, et al.
(författare)
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Cerebrospinal fluid levels of biomarkers and activity of acetylcholinesterase (AChE) and butyrylcholinesterase in AD patients before and after treatment with different AChE inhibitors
- 2002
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Ingår i: Neurological Sciences. - : Springer Science and Business Media LLC. - 1590-1874 .- 1590-3478. ; 23, s. 95-96
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Tidskriftsartikel (refereegranskat)abstract
- In order to evaluate the biochemical effects of long-term treatment with inhibitors of acetylcholinesterase (AChE) in patients with Alzheimer's disease (AD), we measured the activities of AChE and butyry1cholinesterase (BuChe) and the concentrations of beta-amyloid (1-42), tau and phosphorylated tau proteins in the cerebrospinal fluid (CSF). A total of 91 patients suffering from probable AD of mild to moderate degree were treated for 6 months with donepezil (n=59), galantamine (n=15), rivastigmine (n=10), or placebo (n=7). AChE activity in CSF was significantly increased after treatment with donepezil and galantamine; the opposite was observed in the rivastigmine-treated group. Untreated patients did not show any AChE activity variation. BuChE did not show any change in any of the groups studied. Mean values of beta-amyloid(1-42), total tau and phosphorylated tau also did not vary significantly. We conclude that AChE inhibitors induce different effects on CSF AChE activity, while other CSF biomarkers are not significantly affected by treatment.
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- Parnetti, L, et al.
(författare)
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Changes in CSF acetyl- and butyrylcholinesterase activity after long-term treatment with AChE inhibitors in Alzheimer's disease.
- 2011
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Ingår i: Acta neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 124:2, s. 122-129
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Tidskriftsartikel (refereegranskat)abstract
- Objectives - 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). Materials and methods - 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. Results - 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. Conclusions - AChEIs differently influence the activity of target enzymes in CSF independent of their pharmacodynamic effects.
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