Cerebrospinal fluid levels of biomarkers and activity of acetylcholinesterase (AChE) and butyrylcholinesterase in AD patients before and after treatment with different AChE inhibitors.
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 butyrylcholinesterase (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.
Parnetti
L
L
Department of Neuroscience, Perugia University, Perugia, Italy.
Amici
S
S
Lanari
A
A
Romani
C
C
Antognelli
C
C
Andreasen
N
N
Minthon
L
L
Davidsson
P
P
Pottel
H
H
Blennow
K
K
Gallai
V
V
D000110:Acetylcholinesterase / Q000134:cerebrospinal fluid*; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000188:drug therapy* / Q000201:enzymology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002091:Butyrylcholinesterase / Q000134:cerebrospinal fluid*; D002219:Carbamates / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000077265:Donepezil; D004797:Enzyme-Linked Immunosorbent Assay; D005702:Galantamine / Q000494:pharmacology; D006801:Humans; D007189:Indans / Q000494:pharmacology; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D048448:Phenylcarbamates; D010766:Phosphorylation; D010880:Piperidines / Q000494:pharmacology; D000068836:Rivastigmine; D016875:tau Proteins / Q000134:cerebrospinal fluid*
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D002219:Carbamates; D002800:Cholinesterase Inhibitors; D007189:Indans; D010446:Peptide Fragments; D048448:Phenylcarbamates; D010880:Piperidines; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D005702:Galantamine; D000077265:Donepezil; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D000068836:Rivastigmine