Abstract

Previous studies have indicated that acetylcholinesterase (AChE) promotes amyloid-beta -peptide (A beta) fibril formation and AChE-A beta complexes increase A beta -dependent neurotoxicity. Here we present evidence for the: i) identification of the AChE motif that promotes amyloid formation, ii) in vivo effect of AChE on brain plaque formation, and iii) connection between AChE-A beta neurotoxicity and the Wnt signal transduction pathway. Computer modeling, stereotaxic infusions and cell biological techniques were used to study the above problems. Results indicated that a 3.4 kDa AChE peptide promotes A beta fibril formation. AChE infusion into rat hippocampus determines the appearance of anti-A beta and thioflavine-S positive plaques, and AChE-A beta toxicity on hippocampal cultures was blocked by lithium, an activator of the Wnt cascade. We suggest that AChE-A beta /A beta dependent neurotoxicity may result in loss of function of Wnt signaling components, and open the possibility that lithium may be considered as a candidate for therapeutic intervention in Alzheimers disease pathology.