Nc. Inestrosa et al., Acetylcholinesterase-amyloid-beta-peptide interaction and Wnt signaling involvement in A beta neurotoxicity, ACT NEUR SC, 102, 2000, pp. 53-59
Previous studies have indicated that acetylcholinesterase (AChE) promotes a
myloid-beta -peptide (A beta) fibril formation and AChE-A beta complexes in
crease 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 t
o study the above problems. Results indicated that a 3.4 kDa AChE peptide p
romotes A beta fibril formation. AChE infusion into rat hippocampus determi
nes the appearance of anti-A beta and thioflavine-S positive plaques, and A
ChE-A beta toxicity on hippocampal cultures was blocked by lithium, an acti
vator of the Wnt cascade. We suggest that AChE-A beta /A beta dependent neu
rotoxicity may result in loss of function of Wnt signaling components, and
open the possibility that lithium may be considered as a candidate for ther
apeutic intervention in Alzheimers disease pathology.