Changes in CSF acetyl- and butyrylcholinesterase activity after long-term treatment with AChE inhibitors in Alzheimer's disease.
OBJECTIVE
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).


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.
Parnetti
L
L
Clinica Neurologica, Ospedale S. Maria della Misericordia, Università degli studi di Perugia, Perugia, Italy. parnetti@unipg.it
Chiasserini
D
D
Andreasson
U
U
Ohlson
M
M
Hüls
C
C
Zetterberg
H
H
Minthon
L
L
Wallin
A K
AK
Andreasen
N
N
Talesa
V N
VN
Blennow
K
K
D000110:Acetylcholinesterase / Q000097:blood / Q000134:cerebrospinal fluid*; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000134:cerebrospinal fluid* / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D002091:Butyrylcholinesterase / Q000097:blood / Q000134:cerebrospinal fluid*; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D018709:Statistics, Nonparametric; D016875:tau Proteins / Q000134:cerebrospinal fluid
D016229:Amyloid beta-Peptides; D002800:Cholinesterase Inhibitors; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase