Treatment with the selective muscarinic agonist talsaclidine decreases cerebrospinal fluid levels of total amyloid beta-peptide in patients with Alzheimer's disease

Ann N Y Acad Sci. 2000:920:285-91. doi: 10.1111/j.1749-6632.2000.tb06937.x.

Abstract

Brain amyloid load in Alzheimer's disease (AD) is, at least in genetic forms, associated with overproduction of amyloid beta-peptides (A beta). Thus, lowering A beta production is a central therapeutic target in AD and may be achieved by modulating such key enzymes of amyloid precursor protein (APP) processing as beta-, gamma-, and alpha-secretase activities. Talsaclidine is a selective muscarinic M1 agonist that stimulates the nonamyloidogenic alpha-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 A beta were quantitated before and after 4 weeks of drug treatment. We observed that talsaclidine decreases CSF levels of A beta 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 A beta production and may thus be further evaluated as a potential amyloid-lowering therapy of AD.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / drug therapy*
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Double-Blind Method
  • Humans
  • Muscarinic Agonists / therapeutic use*
  • Placebos
  • Quinuclidines / therapeutic use*

Substances

  • Amyloid beta-Peptides
  • Muscarinic Agonists
  • Placebos
  • Quinuclidines
  • talsaclidine fumarate