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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

Darreh-Shori, T. ; Meurling, L. ; Pettersson, T. ; Hugosson, K. ; Hellstrom-Lindahl, E. ; Andreasen, N. ; Minthon, Lennart LU and Nordberg, A. (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)
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author
; ; ; ; ; ; and
organization
publishing date
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
2020-12-08 04:24:08
@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 (&gt;= 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 (&lt;= 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},
  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},
}