Alzheimer Disease

1. Front Matter

   Pages i-xiv

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2. Introductions

   1. Front Matter

      Pages xv-xv

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   2. Development of Drugs for Alzheimer Therapy: A Decade of Progress

      • Ezio Giacobini, Robert Becker

      Pages 1-7

   3. Epidemiology of AD: Impact on the Treatment

      • Luigi Amaducci, Laura Fratiglioni

      Pages 8-13

3. Neuropathologic and Genetic Basis of AD Treatment

   1. Front Matter

      Pages 15-15

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   2. Neuropathological Bases of Alzheimer Disease, Implications for Treatment

      • Henryk M. Wisniewski, Jerzy Wegiel

      Pages 17-22

   3. Amyloid Deposition as the Central Event in the Etiology and Pathogenesis of Alzheimer’s Disease

      • John Hardy, Karen Duff

      Pages 23-27

   4. Role of Abnormal Phosphorylation of Tau in Neurofibrillary Degeneration: Implications for Alzheimer Therapy

      • Khalid Iqbal, Inge Grundke-Iqbal

      Pages 28-33

   5. Olfactory Bulb Involvement in AD: An Early Change

      • Robert G. Struble, Mona Ghobrial, Larry F. Hughes

      Pages 34-40

   6. Alzheimer Disease -- A Spirochetosis?

      • Judit Miklossy

      Pages 41-45

4. Therapeutical Strategies to Arrest Production and Processing of Amyloid

   1. Front Matter

      Pages 47-47

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   2. Beta Amyloid (Aβ) as a Therapeutic Target in Alzheimer’s Disease

      • Ivan Lieberburg

      Pages 49-53

   3. Regulation of APP Processing by First Messengers

      • Roger M. Nitsch, John H. Growdon, Steven A. Farber, Meihua Deng, Richard J. Wurtman

      Pages 54-61

   4. In Vitro Production of Amyloid β-Protein: A Route to the Mechanism and Treatment of Alzheimer’s Disease

      • Dennis J. Selkoe

      Pages 62-64

   5. Apolipoprotein E and Alzheimer’s Disease: Therapeutic Implications

      • Warren J. Strittmatter, David Y. Huang, Ann Saunders, Donald Schmechel, Margaret Pericak-Vance, Allen D. Roses et al.

      Pages 65-71

   6. Apolipoprotein E4 and Cholinergic Dysfunction in Alzheimer’s Disease

      • 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

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   2. Butyrylcholinesterase in Alzheimer’s Disease

      • M.-Marsel Mesulam

      Pages 79-83

   3. Modulating Cholinergic Neurotransmission Through Transgenic Overexpression of Human Cholinesterases

      • Hermona Soreq, Rachel Beeri, Shlomo Seidman, Rina Timberg, Yael Loewenstein, Meira Sternfeld et al.

      Pages 84-87

   4. Structure-Function Relationships in The Binding of Reversible Inhibitors in the Active-Site Gorge of Acetylcholinesterase

      • I. Silman, M. Harel, J. Eichler, J. L. Sussman, A. Anselmet, J. L. Massoulié

      Pages 88-92

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.

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

• School of Medicine, Southern Illinois University, Springfield, USA

  Ezio Giacobini, Robert E. Becker

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