Treatment with the selective muscarinic m1 agonist talsaclidine decreases cerebrospinal fluid levels of A beta 42 in patients with Alzheimer's disease.

The amyloid p-peptides Aβ40 and Aβ42 are highly amyloidogenic constituents of brain Pamyloid plaques in Alzheimer's disease (AD). Lowering their formation may be achieved by modulating the activities of proteases that cleave the amyloid precursor protein (AβPP), including α-β-, and γ-secretases. Talsaclidine is a functionally selective muscarinic ml agonist that stimulates non-amyloidogenic a-secretase processing in vitro. We compared cerebrospinal fluid (CSF) levels of Aβ40 and Aβ42 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 Aβ42 by a median of 19% (p < 0.001) as compared to baseline. The mean diflerence between CSF levels of Aβ42 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 Aβ40 increased during ...