Treatment with the selective muscarinic ml agonist talsaclidine decreases cerebrospinal fluid levels of Aβ42in patients with Alzheimer's disease
| Autor: | Alessia Maddalena, Andri Signorell, Andreas Raschig, Isabella Heuser, Christoph Hock, Harald Hampel, Gerhard W. Eschweiler, Roger M. Nitsch, Klaus Hager, Wolfgang H. Oertel, Franz Müller-Spahn, Charo Gonzalez-Agosti, Marion Wienrich, Thomas Müller-Thomsen |
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| Rok vydání: | 2003 |
| Předmět: |
Agonist
medicine.medical_specialty biology business.industry medicine.drug_class Alpha (ethology) Talsaclidine Cerebrospinal fluid Endocrinology Alpha secretase Internal medicine Muscarinic acetylcholine receptor Internal Medicine Amyloid precursor protein biology.protein Medicine business Beta (finance) |
| Zdroj: | Amyloid. 10:1-6 |
| ISSN: | 1744-2818 1350-6129 |
| DOI: | 10.3109/13506120308995249 |
| Popis: | The amyloid beta-peptides A beta 40 and A beta 42 are highly amyloidogenic constituents of brain beta-amyloid plaques in Alzheimer's disease (AD). Lowering their formation may be achieved by modulating the activities of proteases that cleave the amyloid precursor protein (A beta PP), including alpha- beta-, and gamma-secretases. Talsaclidine is a functionally selective muscarinic m1 agonist that stimulates non-amyloidogenic alpha-secretase processing in vitro. We compared cerebrospinal fluid (CSF) levels of A beta 40 and A beta 42 measured by ELISA before and at the end of 4 weeks of treatment with talsaclidine. The medication was administered in a double-blind, placebo-controlled, and randomized clinical study to 40 patients with AD. Talsaclidine (n = 34) decreased CSF levels of A beta 42 by a median of 19% (p < 0.001) as compared to baseline. The mean difference between CSF levels of A beta 42 before and after treatment with talsaclidine (n = 34) was -46 +/- 73 (SD) pg/ml as compared to 0 +/- 8 (SD) pg/ml with placebo (n = 6) (p < 0.05). CSF levels of A beta 40 increased during treatment with placebo (n = 6) while they remained stable during treatment with talsaclidine (n = 31) (1.118 +/- 1.710 ng/ml, and -0.170 +/- 0.967 ng/ml, respectively; p < 0.05). These data show that treatment with the m1 agonist talsaclidine reduced A beta peptides, and particularly A beta 42, in AD patients, suggesting it as a potential amyloid lowering therapy of AD. |
| Databáze: | OpenAIRE |
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