ACETYLCHOLINESTERASE IS INCREASED IN THE BRAINS OF TRANSGENIC MICE EXPRESSING THE C-TERMINAL FRAGMENT (CT100) OF THE BETA-AMYLOID PROTEIN-PRECURSOR OF ALZHEIMERS-DISEASE

Acetylcholinesterase (AChE) expression is markedly affected in Alzheim er's disease (AD). AChE activity is lower in most regions of the AD br ain, but it is increased within and around amyloid plaques. We have pr eviously shown that AChE expression in P19 cells is increased by the a myloid beta protein (A beta), The aim of this study was to investigate AChE expression using a transgenic mouse model of A beta overproducti on. The beta- actin promoter was used to drive expression of a transge ne encoding the 100-amino acid C-terminal fragment of the human amyloi d precursor protein (APP CT100), Analysis of extracts from transgenic mice revealed that the human sequences of full-length human APP CT100 and A beta were overexpressed in the brain. Levels of salt-extractable AChE isoforms were increased in the brains of APP CT100 mice. There w as also an increase in amphiphilic monomeric form (G(1)(A)) of AChE in the APP CT100 mice, whereas other isoforms were not changed. An incre ase in the proportion of G(1)(A) AChE was also detected in samples of frontal cortex from AD patients. Analysis of AChE by lectin binding re vealed differences in the glycosylation pattern in APP CT100 mice simi lar to those observed in frontal cortex samples from AD. The results a re consistent with the possibility that changes in AChE isoform levels and glycosylation patterns in the AD brain may be a direct consequenc e of altered APP metabolism.