The wheat germ agglutinin‐fractionated proteome of subjects with Alzheimer's disease and mild cognitive impairment hippocampus and inferior parietal lobule: Implications for disease pathogenesis and progression

Lectin affinity chromatography is a powerful separation technique that fractionates proteins by selectively binding to specific carbohydrate moieties characteristic of protein glycosylation type. Wheat germ agglutinin (WGA) selectively binds terminal N‐acetylglucosamine (O‐GlcNAc) and sialic acid moieties characteristic of O‐linked glycosylation. The current study utilizes WGA affinity chromatography to fractionate proteins from hippocampus and inferior parietal lobule (IPL) from subjects with Alzheimer's disease (AD) and arguably its earliest form, mild cognitive impairment (MCI). Proteins identified by proteomics that were fractionated from MCI and AD hippocampus by WGA affinity chromatography with altered levels compared with age‐matched controls included GP96, γ‐enolase, glutamate dehydrogenase, glucosidase IIα, 14‐3‐3ϵ, 14‐3‐3γ, 14‐3‐3ζ, tropomyosin‐2, calmodulin 2, gelsolin, β‐synuclein, α1‐antichymotrypsin, and dimethylguanosine tRNA methyltransferase. Proteins identified by proteomics that were fractionated from MCI and AD IPL by WGA affinity chromatography showing altered levels compared with age‐matched controls included protein disulfide isomerase, calreticulin, and GP96. The proteins described in this study are involved in diverse processes, including glucose metabolism, endoplasmic reticulum (ER) functions, chaperoning, cytoskeletal assembly, and proteolysis, all of which are affected in AD. This study, the first to use proteomics to identify WGA‐fractionated proteins isolated from brains from subjects with MCI and AD, provides additional information about the active proteome of the brain throughout AD progression. © 2010 Wiley‐Liss, Inc.

[1]  T. Lefebvre,et al.  Dysregulation of the nutrient/stress sensor O-GlcNAcylation is involved in the etiology of cardiovascular disorders, type-2 diabetes and Alzheimer's disease. , 2010, Biochimica et biophysica acta.

[2]  D. Butterfield,et al.  Multifunctional roles of enolase in Alzheimer’s disease brain: beyond altered glucose metabolism , 2009, Journal of neurochemistry.

[3]  J. Wegiel,et al.  Gelsolin Levels are Increased in the Brain as a Function of Age During Normal Development in Children That are Further Increased in Down Syndrome , 2009, Alzheimer disease and associated disorders.

[4]  K. Green.  Calcium in the initiation, progression and as an effector of Alzheimer’s disease pathology , 2009, Journal of cellular and molecular medicine.

[5]  Stephen Abela,et al.  Dementia in Malta: Experiences of dementia patients and their caregivers , 2009, Alzheimer's & Dementia.

[6]  W. Scheper,et al.  The unfolded protein response is activated in pretangle neurons in Alzheimer's disease hippocampus. , 2009, The American journal of pathology.

[7]  D. Butterfield,et al.  Proteomics-determined differences in the concanavalin-A-fractionated proteome of hippocampus and inferior parietal lobule in subjects with Alzheimer's disease and mild cognitive impairment: implications for progression of AD. , 2009, Journal of proteome research.

[8]  T. Issad,et al.  O-GlcNAc modification of transcription factors, glucose sensing and glucotoxicity , 2008, Trends in Endocrinology & Metabolism.

[9]  Jeffrey L. Brodsky,et al.  One step at a time: endoplasmic reticulum-associated degradation , 2008, Nature Reviews Molecular Cell Biology.

[10]  Gerald W. Hart,et al.  Cycling of O-linked β-N-acetylglucosamine on nucleocytoplasmic proteins , 2007, Nature.

[11]  H. Paudel,et al.  14-3-3ζ Facilitates GSK3β-catalyzed tau phosphorylation in HEK-293 cells by a mechanism that requires phosphorylation of GSK3β on Ser9 , 2007, Neuroscience Letters.

[12]  J. Keller,et al.  Oxidative inactivation of the proteasome in Alzheimer's disease , 2007, Free radical research.

[13]  D. Butterfield,et al.  REVIEW: Pin1 in Alzheimer's disease , 2006, Journal of neurochemistry.

[14]  Takashi Uehara,et al.  S-Nitrosylated protein-disulphide isomerase links protein misfolding to neurodegeneration , 2006, Nature.

[15]  W. Markesbery,et al.  Decreased RNA, and Increased RNA Oxidation, in Ribosomes from Early Alzheimer’s Disease , 2006, Neurochemical Research.

[16]  F. Baas,et al.  The unfolded protein response affects neuronal cell cycle protein expression: Implications for Alzheimer's disease pathogenesis , 2006, Experimental Gerontology.

[17]  Z. Qin,et al.  Quality control system of the endoplasmic reticulum and related diseases. , 2006, Acta biochimica et biophysica Sinica.

[18]  D. Butterfield,et al.  Proteomic identification of proteins specifically oxidized by intracerebral injection of amyloid β-peptide (1–42) into rat brain: Implications for Alzheimer’s disease , 2005, Neuroscience.

[19]  Frank T Peters,et al.  Toward High-Throughput Drug Screening Using Mass Spectrometry , 2005, Therapeutic drug monitoring.

[20]  F. Baas,et al.  The unfolded protein response is activated in Alzheimer’s disease , 2005, Acta Neuropathologica.

[21]  A. Ritchie,et al.  A new promoter polymorphism in the alpha-1-antichymotrypsin gene is a disease modifier of Alzheimer’s disease , 2005, Neurobiology of Aging.

[22]  Lance Wells,et al.  Quantitative analysis of both protein expression and serine / threonine post‐translational modifications through stable isotope labeling with dithiothreitol , 2005, Proteomics.

[23]  S. Kaushal,et al.  Quality control of integral membrane proteins. , 2004, Trends in biochemical sciences.

[24]  A. Ritchie,et al.  Allele-specific overexpression in astrocytes of an Alzheimer's disease associated alpha-1-antichymotrypsin promoter polymorphism. , 2004, Brain research. Molecular brain research.

[25]  D. Selkoe,et al.  Cell biology of protein misfolding: The examples of Alzheimer's and Parkinson's diseases , 2004, Nature Cell Biology.

[26]  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.

[27]  Y. Takahashi.  The 14-3-3 Proteins: Gene, Gene Expression, and Function , 2003, Neurochemical Research.

[28]  Mark S. Boguski,et al.  Biomedical informatics for proteomics , 2003, Nature.

[29]  Lance Wells,et al.  Mapping Sites of O-GlcNAc Modification Using Affinity Tags for Serine and Threonine Post-translational Modifications* , 2002, Molecular & Cellular Proteomics.

[30]  Visith Thongboonkerd,et al.  Proteomic analysis of normal human urinary proteins isolated by acetone precipitation or ultracentrifugation. , 2002, Kidney international.

[31]  C. Schutt,et al.  Tropomyosin and Gelsolin Cooperate in Controlling the Microfilament System* , 2002, The Journal of Biological Chemistry.

[32]  Michael B Yaffe,et al.  How do 14‐3‐3 proteins work? – Gatekeeper phosphorylation and the molecular anvil hypothesis , 2002, FEBS letters.

[33]  J. George,et al.  The synucleins , 2001, Genome Biology.

[34]  R. Cole,et al.  Cytosolic O‐glycosylation is abundant in nerve terminals , 2001, Journal of neurochemistry.

[35]  J. Trojanowski,et al.  Altered expression of the synuclein family mRNA in Lewy body and Alzheimer’s disease , 2001, Brain Research.

[36]  Dottie M. Clower,et al.  The Inferior Parietal Lobule Is the Target of Output from the Superior Colliculus, Hippocampus, and Cerebellum , 2001, The Journal of Neuroscience.

[37]  G. Hart,et al.  O-Glycosylation of Nuclear and Cytosolic Proteins , 2000, The Journal of Biological Chemistry.

[38]  J. Trojanowski,et al.  Synucleins Are Developmentally Expressed, and α-Synuclein Regulates the Size of the Presynaptic Vesicular Pool in Primary Hippocampal Neurons , 2000, The Journal of Neuroscience.

[39]  W. V. Van Nostrand,et al.  Plasmin cleavage of the amyloid beta-protein: alteration of secondary structure and stimulation of tissue plasminogen activator activity. , 1999, Biochemistry.

[40]  J. Serratosa,et al.  The Ca2+/calmodulin signaling system in the neural response to excitability. involvement of neuronal and glial cells , 1999, Progress in Neurobiology.

[41]  P. Csermely,et al.  Associate Editor: D. Shugar The 90-kDa Molecular Chaperone Family: Structure, Function, and Clinical Applications. A Comprehensive Review , 1998 .

[42]  W. Markesbery.  Neuropathological Criteria for the Diagnosis of Alzheimer’s Disease , 1997, Neurobiology of Aging.

[43]  K. Meguro,et al.  Decreased cortical glucose metabolism correlates with hippocampal atrophy in Alzheimer's disease as shown by MRI and PET. , 1997, Journal of neurology, neurosurgery, and psychiatry.

[44]  D. Butterfield,et al.  α1-Antichymotrypsin interaction with Aβ(1–42) does not inhibit fibril formation but attenuates the peptide toxicity , 1996, Neuroscience Letters.

[45]  B K Hayes,et al.  O-GlcNAcylation of key nuclear and cytoskeletal proteins: reciprocity with O-phosphorylation and putative roles in protein multimerization. , 1996, Glycobiology.

[46]  D. Butterfield,et al.  α-1-Antichymotrypsin interaction with Aβ (1–40) inhibits fibril formation but does not affect the peptide toxicity , 1996, Neuroscience Letters.

[47]  M. Quadroni,et al.  Isolation of phosphorylated calmodulin from rat liver and identification of the in vivo phosphorylation sites. , 1994, The Journal of biological chemistry.

[48]  S. Stamm,et al.  Brain-specific tropomyosins TMBr-1 and TMBr-3 have distinct patterns of expression during development and in adult brain. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[49]  J. Williams,et al.  Phosphorylation by casein kinase II alters the biological activity of calmodulin. , 1992, The Biochemical journal.

[50]  W. Welch,et al.  Characterization and purification of the 94-kDa glucose-regulated protein. , 1991, The Journal of biological chemistry.

[51]  P. Mcgeer,et al.  Activation of the classical complement pathway in brain tissue of Alzheimer patients , 1989, Neuroscience Letters.

[52]  Z. Khachaturian.  Introduction and Overview , 1989, Annals of the New York Academy of Sciences.

[53]  G. Koch,et al.  Perturbation of cellular calcium induces secretion of luminal ER proteins , 1989, Cell.

[54]  D. Selkoe,et al.  Immunochemical identification of the serine protease inhibitor α 1-antichymotrypsin in the brain amyloid deposits of Alzheimer's disease , 1988, Cell.

[55]  L Sikorski,et al.  Calmodulin , 2020, Definitions.

[56]  A. Means,et al.  Control of microtubule assembly-disassembly by calcium-dependent regulator protein. , 1978, Proceedings of the National Academy of Sciences of the United States of America.

[57]  G. O'Neill,et al.  Tropomyosin-based regulation of the actin cytoskeleton in time and space. , 2008, Physiological reviews.

[58]  G. Hart,et al.  Cycling of O-linked beta-N-acetylglucosamine on nucleocytoplasmic proteins. , 2007, Nature.

[59]  H. Paudel,et al.  14-3-3zeta facilitates GSK3beta-catalyzed tau phosphorylation in HEK-293 cells by a mechanism that requires phosphorylation of GSK3beta on Ser9. , 2007, Neuroscience letters.

[60]  D. Butterfield,et al.  Redox proteomics identification of oxidatively modified brain proteins in Alzheimer's disease and mild cognitive impairment: insights into the progression of this dementing disorder. , 2007 .

[61]  S. Hoyer.  Causes and consequences of disturbances of cerebral glucose metabolism in sporadic Alzheimer disease: therapeutic implications. , 2004, Advances in experimental medicine and biology.

[62]  G. Lubec,et al.  Aberrant expression of signaling‐related proteins 14‐3‐3 gamma and RACK1 in fetal Down Syndrome brain (trisomy 21) , 2002, Electrophoresis.

[63]  S. Masters,et al.  14-3-3 proteins: structure, function, and regulation. , 2000, Annual review of pharmacology and toxicology.

[64]  N. Cairns,et al.  Increased levels of 14-3-3 gamma and epsilon proteins in brain of patients with Alzheimer's disease and Down syndrome. , 1999, Journal of neural transmission. Supplementum.

[65]  G. Hart,et al.  Dynamic O-linked glycosylation of nuclear and cytoskeletal proteins. , 1997, Annual review of biochemistry.

[66]  D. Butterfield,et al.  Alpha 1-antichymotrypsin interaction with A beta (1-42) does not inhibit fibril formation but attenuates the peptide toxicity. , 1996, Neuroscience letters.

[67]  D. Butterfield,et al.  alpha-1-antichymotrypsin interaction with A beta (1-40) inhibits fibril formation but does not affect the peptide toxicity. , 1996, Neuroscience letters.

[68]  G. Perry,et al.  Immunochemical demonstration of tropomyosin in the neurofibrillary pathology of Alzheimer's disease. , 1990, The American journal of pathology.

[69]  H. Potter,et al.  Alpha 1-antichymotrypsin in brain aging and disease. , 1989, Progress in clinical and biological research.

[70]  H. Potter,et al.  The protease inhibitor, alpha 1-antichymotrypsin, is a component of the brain amyloid deposits in normal aging and Alzheimer's disease. , 1989, Annals of medicine.

[71]  H. Potter,et al.  The Protease Inhibitor, α1-Antichymotrypsin, Is a Component of the Brain Amyloid Deposits in Normal Aging and Alzheimer's Disease , 1989 .

[72]  B. González,et al.  Ca2+-calmodulin tubulin kinase system and its role in mediating the Ca2+ signal in brain. , 1982, Progress in brain research.