BRAIN ACETYLCHOLINESTERASE PROMOTES AMYLOID-BETA-PEPTIDE AGGREGATION BUT DOES NOT HYDROLYZE AMYLOID PRECURSOR PROTEIN-PEPTIDES

It has been suggested that acetylcholinesterase (AChE) has both a puta tive proteolytic activity against the amyloid precursor protein (APP), and a capacity to accelerate the assembly of amyloid-beta-peptide (A beta) into Alzheimer's fibrils. Here, we have studied the ability of b ovine brain AChE to share both activities. Results indicate that AChE purified through acridinium was able to process the APP peptides, howe ver after further purification by an edrophonium column, the protease activity was lost. Under both conditions the capacity of the enzyme to promote amyloid formation was maintained. Kinetic studies of the A be ta aggregation process using edrophonium-AChE, indicated that the lag phase of the aggregation process was smaller than the one observed wit h the esterase purified by acridinium alone. Considering that the tota l amount of amyloid formed, measured by thioflavine-T fluorescence, wa s similar for both AChE preparations, our results suggest that the edr ophonium-AChE possesses an higher intrinsic capacity to stimulate the aggregation of A beta(1-40) peptide.