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 (>or=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 (<or=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.
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 ADpatients. 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 (>or=45%) showed a stabilized MMSE test result after up to two years, while a significant decline was observed in ADpatients with lower AChE inhibition (<or=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.
Authors: M Shapira; I Tur-Kaspa; L Bosgraaf; N Livni; A D Grant; D Grisaru; M Korner; R P Ebstein; H Soreq Journal: Hum Mol Genet Date: 2000-05-22 Impact factor: 6.150
Authors: Valtteri Kaasinen; Kjell Någren; Tarja Järvenpää; Anne Roivainen; Meixiang Yu; Vesa Oikonen; Timo Kurki; Juha O Rinne Journal: J Clin Psychopharmacol Date: 2002-12 Impact factor: 3.153
Authors: R M Nitsch; S Rossner; C Albrecht; M Mayhaus; J Enderich; R Schliebs; M Wegner; T Arendt; H von der Kammer Journal: J Physiol Paris Date: 1998 Jun-Aug
Authors: Alberto Lleó; Enrica Cavedo; Lucilla Parnetti; Hugo Vanderstichele; Sanna Kaisa Herukka; Niels Andreasen; Roberta Ghidoni; Piotr Lewczuk; Andreas Jeromin; Bengt Winblad; Magda Tsolaki; Barbara Mroczko; Pieter Jelle Visser; Isabel Santana; Per Svenningsson; Kaj Blennow; Dag Aarsland; José Luis Molinuevo; Henrik Zetterberg; Brit Mollenhauer Journal: Nat Rev Neurol Date: 2014-12-16 Impact factor: 42.937