Acetylcholinesterase and butyrylcholinesterase glycoforms are biomarkers of Alzheimer's disease

The identification of a biochemical marker in cerebrospinal fluid (CSF) that can discriminate between Alzheimer's disease (AD) and other dementia-causing diseases would be a major advance. Our previous studies have shown that the glycosylation of acetylcholinesterase (AChE) is altered in the post mortem brain and cerebrospinal fluid of AD patients. We have also found that the glycosylation of AChE is altered in lumbar CSF collected ante mortem. The change in glycosylation of AChE is very specific for AD and is not seen in many other neurological diseases including other dementias. The sensitivity of detection of AD using AChE glycosylation (60-80%) is lower than that considered necessary for a satisfactory diagnostic marker. However, more recently we have found that the glycosylation of the related enzyme butyrylcholinesterase (BuChE) is also altered in AD CSF. By combining the analysis of AChE glycosylation with that of BuChE glycosylation, improved sensitivity of detection is obtained. We propose that AChE and BuChE glycosylation may be of diagnostic value, especially when used in combination with other CSF markers such as Aβ or tau.