STABLE COMPLEXES INVOLVING ACETYLCHOLINESTERASE AND AMYLOID-BETA PEPTIDE CHANGE THE BIOCHEMICAL-PROPERTIES OF THE ENZYME AND INCREASE THE NEUROTOXICITY OF ALZHEIMERS FIBRILS

Brain acetylcholinesterase (AChE) forms stable complexes with amyloid- beta peptide (A beta) during its assembly into filaments, in agreement with its colocalization with the A beta deposits of Alzheimer's brain . The association of the enzyme with nascent A beta aggregates occurs as early as after 30 min of incubation. Analysis of the catalytic acti vity of the AChE incorporated into these complexes shows an anomalous behavior reminiscent of the AChE associated with senile plaques, which includes a resistance to low pH, high substrate concentrations, and l ower sensitivity to AChE inhibitors. Furthermore, the toxicity of the AChE-amyloid complexes is higher than that of the A beta aggregates al one. Thus, in addition to its possible role as a heterogeneous nucleat or during amyloid formation, AChE, by forming such stable complexes, m ay increase the neurotoxicity of A beta fibrils and thus may determine the selective neuronal loss observed in Alzheimer's brain.