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Alzheimer Disease

Therapeutic Strategies

  • Ezio Giacobini
  • Robert E. Becker

Part of the Advances in Alzheimer Disease Therapy book series (AADT)

Table of contents

  1. Front Matter
    Pages i-xiv
  2. Introductions

    1. Front Matter
      Pages xv-xv
    2. Luigi Amaducci, Laura Fratiglioni
      Pages 8-13
  3. Neuropathologic and Genetic Basis of AD Treatment

    1. Front Matter
      Pages 15-15
    2. Henryk M. Wisniewski, Jerzy Wegiel
      Pages 17-22
    3. Robert G. Struble, Mona Ghobrial, Larry F. Hughes
      Pages 34-40
    4. Judit Miklossy
      Pages 41-45
  4. Therapeutical Strategies to Arrest Production and Processing of Amyloid

    1. Front Matter
      Pages 47-47
    2. Roger M. Nitsch, John H. Growdon, Steven A. Farber, Meihua Deng, Richard J. Wurtman
      Pages 54-61
    3. Warren J. Strittmatter, David Y. Huang, Ann Saunders, Donald Schmechel, Margaret Pericak-Vance, Allen D. Roses et al.
      Pages 65-71
    4. Judes Poirier, Isabelle Aubert, Philippe Bertrand, Rémi Quirion, Serge Gauthier, Josephine Nalbantoglu
      Pages 72-76
  5. The Cholinergic System of Human Brain

    1. Front Matter
      Pages 77-77
    2. M.-Marsel Mesulam
      Pages 79-83
    3. Hermona Soreq, Rachel Beeri, Shlomo Seidman, Rina Timberg, Yael Loewenstein, Meira Sternfeld et al.
      Pages 84-87
    4. I. Silman, M. Harel, J. Eichler, J. L. Sussman, A. Anselmet, J. L. Massoulié
      Pages 88-92
    5. Steven T. DeKosky, Scot D. Styren, Mark E. O’Malley
      Pages 93-96
  6. Cholinesterase Inhibitors in AD Treatment

    1. Front Matter
      Pages 97-97
    2. Nicola Canal, Massimo Franceschi, Italian Eptastigmine Investigators
      Pages 108-112
    3. Xi Can Tang, Zhi Qi Xiong, Bo Chu Qian, Zhi Fang Zhou, Ci Lu Zhang
      Pages 113-119
    4. Mark R. Emmerling, Vlad E. Gregor, Roy D. Schwarz, Jeff D. Scholten, Michael J. Callahan, Chitase Lee et al.
      Pages 120-124
    5. Jean-Marie Hornsperger, Jean-Noël Collard, Daniel Schirlin, James Dow, Jean-Georges Heydt, Bertrand Duléry
      Pages 131-136
    6. Margo M. Schleman, Stephen S. Songer, Olo J. Szylleyko, Randall D. Seifert, Neal R. Cutler
      Pages 137-139
    7. Helmut Kewitz, Gordon Wilcock, Bonnie Davis
      Pages 140-144
    8. Stephen I. Gracon, Margaret J. Knapp
      Pages 145-149
    9. Klaudius Siegfried, Rich Civil
      Pages 150-154
    10. Robert E. Becker, Pamela Moriearty, Rita Surbeck, Latha Unni, Andrew Varney, Sandra K. Vicari
      Pages 172-178
  7. Nicotinic Agonists as Drugs for AD Treatment

    1. Front Matter
      Pages 179-179
    2. Hannsjörg Schröder, Andrea Wevers, Christina Birtsch, Mona Ghobrial, Ezio Giacobini, Alfred Maelicke
      Pages 181-185
    3. Patrick M. Lippiello, William S. Caldwell, Michael J. Marks, Allan C. Collins
      Pages 186-190
    4. Paul A. Newhouse, Alexandra Potter, June Corwin, Robert Lenox
      Pages 191-195
    5. Stephen P. Arneric, James P. Sullivan, Michael W. Decker, Jorge D. Brioni, Clark A. Briggs, Diana Donnelly-Roberts et al.
      Pages 196-200
    6. Jeffrey A. Gray, Grigory A. Grigoryan, Chuly Lee, Stephen N. Mitchell, Helen Hodges
      Pages 201-205
    7. Roger L. Papke, Christopher M. de Fiebre, William Kem, Edwin M. Meyer
      Pages 206-211
    8. Paavo J. Riekkinen Jr., Minna K. Riekkinen, Jouni S. Sirviö
      Pages 212-216
  8. Muscarinic Agonists: Preclinical and Clinical Approaches

    1. Front Matter
      Pages 217-217
    2. Abraham Fisher, Eliahu Heldman, David Gurwitz, Rachel Haring, Yishai Karton, Haim Meshulam et al.
      Pages 219-223
    3. Roy D. Schwarz, Michael J. Callahan, Robert E. Davis, Juan C. Jaen, William Lipinski, Charlotte Raby et al.
      Pages 224-228
    4. Harlan E. Shannon, Frank P. Bymaster, David O. Calligaro, Beverley Greenwood, Charles H. Mitch, John S. Ward et al.
      Pages 229-233
    5. N. C. Bodick, A. F. DeLong, P. L. Bonate, T. Gillespie, D. P. Henry, J. H. Satterwhite et al.
      Pages 234-238
  9. Drugs to Enhance Acetylcholine Synthesis and Release

    1. Front Matter
      Pages 245-245

About these proceedings

Introduction

Since the apoE4 allele is a risk factor or susceptibility gene in late-onset familial and sporadic AD, the mechanism of disease expression may involve metabolic effects that are isoform specific. Isoform-specific interactions of apoE therefore become critical in the mechanism of AD pathogenesis. Detailed characterization of the binding of the apoE isoforms with proteins and peptides relevant to the pathology of the disease may be critical in understanding disease pathogenesis. These critical isoform-specific interactions of apoE may involve interactions with proteins and pep tides in the defining neuropathologic lesions of the disease, the neurofibrillary tangle and senile plaque. Other possible critical isoform-specific interactions include the mechanism of internalization, intracellular trafficking, and subsequent metabolism. In addition, differential post-translational modifications of apoE isoforms may determine differences in metabolism contributing to the pathogenesis of the disease. Oxidation of apoE may confer several isoform-specific, biochemically distinct properties. Since {3A peptide binds apoE in the lipoprotein binding domain of the protein and not in the receptor-binding domain, apoE could target bound {3A4 peptide to neurons via the LRP receptor. Internalization of the apoEI {3A peptide complex into the cell, by the same route as the apoE-containing lipoproteins, would result in incorporation into primary lysosomes and pH dependent dissociation. The demonstration of apoE in the cytoplasm of neurons, with isoform-specific interactions of apoE with the microtubule-binding protein tau demonstrated in vitro, suggest additional, testable hypotheses of disease pathogenesis.

Keywords

Alzheimer's disease Alzheimer´s disease cell diagnosis gene management metabolism neurons pathology peptides pharmacology protein proteins therapy treatment

Editors and affiliations

  • Ezio Giacobini
    • 1
  • Robert E. Becker
    • 1
  1. 1.School of MedicineSouthern Illinois UniversitySpringfieldUSA

Bibliographic information