Abstract

The major protein constituent of amyloid deposits in Alzheimer's disease (AD) is the amyloid-β-peptide (Aβ). Amyloid deposits contain "chaperone molecules" which play critical roles in amyloid formation and toxicity. In the present work, we test an analog of hyperforin (IDN 5706) which releases the AChE from both the Aβ fibrils and the AChE-Aβ burdens in transgenic mice. Hyperforin is an acylphloroglucinol compound isolated from Hypericum perforatum (St. John's Wort), which is able to prevent the Aβ-induced spatial memory impairments and Aβ neurotoxicity. Altogether this gathered evidence indicates the important role of AChE in the neurotoxicity of Aβ plaques and finding new compounds which decrease the AChE-Aβ interaction may be a putative therapeutic agent to fight the disease. © 2008 Elsevier Ireland Ltd. All rights reserved.