Molecular Isoform Distribution and Glycosylation of Acetylcholinesterase Are Altered in Brain and Cerebrospinal Fluid of Patients with Alzheimer’s Disease

Authors


  • Lippincott Williams & Wilkins, Inc., Philadelphia

  • Abbreviations used: Aβ, β-amyloid protein; AChE, acetylcholinesterase; AD, Alzheimer’s disease; AF, amphiphilic fraction; ChE, cholinesterase; C/W ratio, percentage of acetylcholinesterase that does not bind to concanavalin A divided by percentage of acetylcholinesterase that does not bind to wheat germ agglutinin; DP, diffuse plaque; Ga, globular amphiphilic isoform; Gna, globular nonamphiphilic isoform; HF, hydrophilic fraction; ND, other neurological disease; PMI, postmortem interval; SS, salt-soluble supernatant; TS, Triton X-100-soluble supernatant; TSB, Tris-saline buffer; and agglutinins from Canavalia ensiformis (concanavalin A), Con A; Triticum vulgaris (wheat germ), WGA; Ricinus communis, RCA120; Lens culinaris, LCA; Dolichus biflorus, DBA; Ulex europaeus, EUAI; Glycine max (soybean), SBA; and Arachis hypogaea, PNA.

Address correspondence and reprint requests to Dr. D. H. Small at Department of Pathology, University of Melbourne, Parkville, Victoria 3052, Australia.

Abstract

Abstract: The glycosylation of acetylcholinesterase (AChE) in CSF was analyzed by lectin 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 and brain, we examined whether the abnormal glycosylation of AD AChE was due to changes in a specific molecular isoform. Globular amphiphilic dimeric (G2a) and monomeric (G1a) isoforms of AChE were found to be differentially glycosylated in AD CSF. Glycosylation of AChE was also altered in AD frontal cortex but not in cerebellum and was also associated with an increase in the proportion of light (G2 and G1) isoforms. This study demonstrates that the glycosylation of AChE is altered in the AD brain and that changes 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.

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