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Treatment With the Selective Muscarinic m1 Agonist Talsaclidine Decreases Cerebrospinal Fluid Levels of A Beta 42 in Patients With Alzheimer's Disease

Treatment With the Selective Muscarinic m1 Agonist Talsaclidine Decreases Cerebrospinal Fluid Levels of A Beta 42 in Patients With Alzheimer's Disease

Christoph Hock, Alessia Maddalena, Andreas Raschig, Franz Müller-Spahn, Gerhard Eschweiler, Klaus Hager, Isabella Heuser, Harald Hampel, Thomas Müller-Thomsen, Wolfgang Oertel, Marion Wienrich, Andri Signorell, etc.

Amyloid. 2003 Mar;10(1):1-6.

PMID: 12762134

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP147025534	Talsaclidine		147025-53-4	Price

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