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Treatment with the Selective Muscarinic Agonist Talsaclidine Decreases Cerebrospinal Fluid Levels of Total Amyloid β‐Peptide in Patients with Alzheimer's Disease
Author(s) -
HOCK C.,
MADDALENA A.,
HEUSER I.,
NABER D.,
OERTEL W.,
KAMMER H.,
WIENRICH M.,
RASCHIG A.,
DENG M.,
GROWDON J. H.,
NITSCH R. M.
Publication year - 2000
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2000.tb06937.x
Subject(s) - cerebrospinal fluid , agonist , beta (programming language) , amyloid (mycology) , endocrinology , amyloid beta , medicine , alzheimer's disease , senile plaques , amyloid precursor protein , placebo , pharmacology , chemistry , disease , receptor , pathology , computer science , programming language , alternative medicine
A bstract : Brain amyloid load in Alzheimer's disease (AD) is, at least in genetic forms, associated with overproduction of amyloid β‐peptides (Aβ). Thus, lowering Aβ production is a central therapeutic target in AD and may be achieved by modulating such key enzymes of amyloid precursor protein (APP) processing as β‐, γ‐, and α‐secretase activities. Talsaclidine is a selective muscarinic M1 agonist that stimulates the nonamyloidogenic α‐secretase pathway in model systems. Talsaclidine was administered double‐blind, placebo‐controlled, and randomized to 24 AD patients and cerebrospinal fluid (CSF) levels of total Aβ were quantitated before and after 4 weeks of drug treatment. We observed that talsaclidine decreases CSF levels of Aβ significantly over time within the treatment group ( n =20 ) by a median of 16% as well as compared to placebo ( n =4 ) by a median of 27%. We conclude that treatment with selective M1 agonists may reduce Aβ production and may thus be further evaluated as a potential amyloid‐lowering therapy of AD.