Molecular isoform distribution and glycosylation of acetylcholinesterase are altered in brain and cerebrospinal fluid of patients with Alzheimer's disease

The glycosylation of acetylcholinesterase (AChE) in CSF was analyzed by lec tin binding. AChE from Alzheimer's disease (AD) patients was found to bind differently to two lectins, concanavalin A and wheat germ agglutinin, than AChE from controls. As multiple isoforms of AChE are present in both CSF an d brain, we examined whether the abnormal glycosylation of AD AChE was due to changes in a specific molecular isoform. Globular amphiphilic dimeric (G (2)(a))and monomeric (G(1)(a)) isoforms of AChE were found to be differenti ally glycosylated in AD CSF, Glycosylation of AChE was also altered in AD f rontal colter but not in cerebellum and was also associated with an increas e in the proportion of light (G(2) and G(1)) isoforms. This study demonstra tes that the glycosylation of AChE is altered in the AD brain and that chan ges in AChE glycosylation in AD CSF may reflect changes in the distribution of brain isoforms. The study also suggests that glycosylation of AChE may be a useful diagnostic marker for AD.