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) In Journal of Neural Transmission 113(11). p.1791-1801- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/685852
- author
- Darreh-Shori, T. ; Meurling, L. ; Pettersson, T. ; Hugosson, K. ; Hellstrom-Lindahl, E. ; Andreasen, N. ; Minthon, Lennart LU and Nordberg, A.
- organization
- publishing date
- 2006
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- cerebrospinal fluid (CSF), cholinesterase inhibitors, variants, acetylcholinesterase splice, Alzheimer's disease, acetylcholinesterase, chronic treatment, blood cells (RBC), red, donepezil
- in
- Journal of Neural Transmission
- volume
- 113
- issue
- 11
- pages
- 1791 - 1801
- publisher
- Springer
- external identifiers
-
- wos:000241611700021
- scopus:33750472319
- ISSN
- 0300-9564
- DOI
- 10.1007/s00702-006-0526-2
- language
- English
- LU publication?
- yes
- id
- d4747db0-a9c2-4e52-a516-33ac09a90753 (old id 685852)
- date added to LUP
- 2016-04-01 16:13:54
- date last changed
- 2022-03-22 17:16:51
@article{d4747db0-a9c2-4e52-a516-33ac09a90753,
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.}},
author = {{Darreh-Shori, T. and Meurling, L. and Pettersson, T. and Hugosson, K. and Hellstrom-Lindahl, E. and Andreasen, N. and Minthon, Lennart and Nordberg, A.}},
issn = {{0300-9564}},
keywords = {{cerebrospinal fluid (CSF); cholinesterase inhibitors; variants; acetylcholinesterase splice; Alzheimer's disease; acetylcholinesterase; chronic treatment; blood cells (RBC); red; donepezil}},
language = {{eng}},
number = {{11}},
pages = {{1791--1801}},
publisher = {{Springer}},
series = {{Journal of Neural Transmission}},
title = {{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}},
url = {{http://dx.doi.org/10.1007/s00702-006-0526-2}},
doi = {{10.1007/s00702-006-0526-2}},
volume = {{113}},
year = {{2006}},
}