Altered glycosylation of acetylcholinesterase in Creutzfeldt–Jakob disease

Changes in the glycosylation pattern of brain proteins have been associated with Creutzfeldt–Jakob disease (CJD). We have investigated the glycosylation status of acetylcholinesterase (AChE) by lectin binding assay. Our data show that in lumbar CSF from definite and probable sporadic CJD cases AChE activity is lower compared with that in age‐matched controls. We also show, for the first time, that AChE glycosylation is altered in CJD CSF and brain. Unlike Alzheimer's disease, in which an alteration in both the glycosylation and levels of AChE molecular forms is observed, the abnormal glycosylation of AChE in CJD appears to be unrelated to changes in molecular forms of this enzyme. These findings suggest that altered AChE glycosylation in CJD may be a consequence of the general perturbation of the glycosylation machinery that affects prion protein, as well as other proteins. The diagnostic potential of these changes remains to be explored.

[1]  S. Prusiner,et al.  Glycosylation differences between the normal and pathogenic prion protein isoforms. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[2]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[3]  D. Small,et al.  Altered glycosylation of acetylcholinesterase in lumbar cerebrospinal fluid of patients with Alzheimer's disease , 2000, Journal of neurology, neurosurgery, and psychiatry.

[4]  C. Geula,et al.  Anatomy of cholinesterase inhibition in Alzheimer's disease: Effect of physostigmine and tetrahydroaminoacridine on plaques and tangles , 1987, Annals of neurology.

[5]  Y. Ashani,et al.  Structure of glycan moieties responsible for the extended circulatory life time of fetal bovine serum acetylcholinesterase and equine serum butyrylcholinesterase. , 1997, Biochemistry.

[6]  Yutaka Kirino,et al.  Cleavage of Alzheimer’s Amyloid Precursor Protein (APP) by Secretases Occurs after O-Glycosylation of APP in the Protein Secretory Pathway , 1998, The Journal of Biological Chemistry.

[7]  A. Gnatt,et al.  Molecular cloning and construction of the coding region for human acetylcholinesterase reveals a G + C-rich attenuating structure. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[8]  Robert H. Perry,et al.  Molecular forms of acetylcholinesterase in senile dementia of Alzheimer type: Selective loss of the intermediate (10S) form , 1983, Neuroscience Letters.

[9]  P. Codogno,et al.  Evolving views in prion glycosylation: functional and pathological implications. , 2003, Biochimie.

[10]  S. Brimijoin,et al.  Acetylcholinesterase promotes beta-amyloid plaques in cerebral cortex , 2003, Neurobiology of Aging.

[11]  D. Small,et al.  Non-classical actions of cholinesterases: Role in cellular differentiation, tumorigenesis and Alzheimer's disease , 1996, Neurochemistry International.

[12]  T. Bergman,et al.  Increased levels of insulin and insulin-like growth factor-1 hybrid receptors and decreased glycosylation of the insulin receptor alpha- and beta-subunits in scrapie-infected neuroblastoma N2a cells. , 2004, The Biochemical journal.

[13]  F. Vallette,et al.  Molecular and cellular biology of cholinesterases , 1993, Progress in Neurobiology.

[14]  J. Wade,et al.  The clinical diagnosis of Alzheimer's disease. , 1987, Archives of neurology.

[15]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease , 1984, Neurology.

[16]  C. Masters,et al.  Glycosylation of acetylcholinesterase as diagnostic marker for Alzheimer's disease , 1997, The Lancet.

[17]  N. Robinson.  Creutzfeldt-Jakob's disease: a histochemical study. , 1969, Brain : a journal of neurology.

[18]  S. Kitazume,et al.  Alzheimer's β-secretase, β-site amyloid precursor protein-cleaving enzyme, is responsible for cleavage secretion of a Golgi-resident sialyltransferase , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[19]  G. Hart,et al.  O-GlcNAcylation regulates phosphorylation of tau: a mechanism involved in Alzheimer's disease. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[20]  B. Crain,et al.  Interlaboratory Comparison of Neuropathology Assessments in Alzheimer's Disease: A Study of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) , 1994, Journal of neuropathology and experimental neurology.

[21]  T. Arendt,et al.  Changes in acetylcholinesterase and butyrylcholinesterase in Alzheimer's disease resemble embryonic development—A study of molecular forms , 1992, Neurochemistry International.

[22]  S. Bernard,et al.  Interactions with lectins indicate differences in the carbohydrate composition of the membrane-bound enzymes acetylcholinesterase and 5'-nucleotidase in different cell types. , 1984, Biochimie.

[23]  E. Zenteno,et al.  Altered Glycosylation Pattern of Proteins in Alzheimer Disease , 1998, Journal of neuropathology and experimental neurology.

[24]  J. Kornhuber,et al.  Decreased β-amyloid1-42 in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease , 2000, Neurology.

[25]  Pauline M Rudd,et al.  Glycosylation and prion protein. , 2002, Current opinion in structural biology.

[26]  A. Shafferman,et al.  N-glycosylation of human acetylcholinesterase: effects on activity, stability and biosynthesis. , 1993, The Biochemical journal.

[27]  T. Arendt.  Alzheimer’s disease as a loss of differentiation control in a subset of neurons that retain immature features in the adult brain , 2000, Neurobiology of Aging.

[28]  S. Kitazume,et al.  Alzheimer's beta-secretase, beta-site amyloid precursor protein-cleaving enzyme, is responsible for cleavage secretion of a Golgi-resident sialyltransferase. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[29]  Claudia Linker,et al.  Acetylcholinesterase Accelerates Assembly of Amyloid-β-Peptides into Alzheimer's Fibrils: Possible Role of the Peripheral Site of the Enzyme , 1996, Neuron.

[30]  P. Agostinho,et al.  Involvement of oxidative stress in the enhancement of acetylcholinesterase activity induced by amyloid beta-peptide , 2003, Neuroscience Research.

[31]  P. Layer.  Nonclassical roles of cholinesterases in the embryonic brain and possible links to Alzheimer disease. , 1995, Alzheimer disease and associated disorders.

[32]  P. Layer.  Non-classical actions of cholinesterases: Role in cellular differentiation, tumorigenesis and Alzheimer's disease , 1996, Neurochemistry International.

[33]  I. Alafuzoff,et al.  Glycosylation changes in Alzheimer’s disease as revealed by a proteomic approach , 2004, Neuroscience Letters.

[34]  H. Budka,et al.  Analysis of EEG and CSF 14-3-3 proteins as aids to the diagnosis of Creutzfeldt–Jakob disease , 2000, Neurology.

[35]  H. Soreq,et al.  Acetylcholinesterase — new roles for an old actor , 2001, Nature Reviews Neuroscience.

[36]  D. Small,et al.  Molecular Isoform Distribution and Glycosylation of Acetylcholinesterase Are Altered in Brain and Cerebrospinal Fluid of Patients with Alzheimer’s Disease , 1999, Journal of neurochemistry.

[37]  H. Deng,et al.  Scrapie strain infection in vitro induces changes in neuronal cells , 1994, Molecular Neurobiology.

[38]  D. Small,et al.  Wheat germ agglutinin‐binding glycoproteins are decreased in Alzheimer's disease cerebrospinal fluid , 2001, Journal of neurochemistry.

[39]  S. Sorbi,et al.  Choline acetyltransferase and acetylcholinesterase abnormalities in senile dementia: Importance of biochemical measurements in human post-mortem brain specimens , 1979, The Italian Journal of Neurological Sciences.

[40]  J. Kornhuber,et al.  Decreased beta-amyloid1-42 in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease. , 2000, Neurology.

[41]  C. Masters,et al.  The Amyloid β‐Protein of Alzheimer's Disease Increases Acetylcholinesterase Expression by Increasing Intracellular Calcium in Embryonal Carcinoma P19 Cells , 1997, Journal of neurochemistry.

[42]  S. Brimijoin,et al.  Amyloid‐beta increases acetylcholinesterase expression in neuroblastoma cells by reducing enzyme degradation , 2003, Journal of neurochemistry.

[43]  H. Wiśniewski,et al.  Brain glutamate decarboxylase and cholinergic enzyme activities in scrapie , 1985, Journal of the Neurological Sciences.

[44]  C. Masters,et al.  Acetylcholinesterase Is Increased in the Brains of Transgenic Mice Expressing the C‐Terminal Fragment (CT100) of the β‐Amyloid Protein Precursor of Alzheimer's Disease , 1998, Journal of neurochemistry.