Overview
- Editors:
-
-
Ezio Giacobini
-
School of Medicine, Southern Illinois University, Springfield, USA
-
Robert E. Becker
-
School of Medicine, Southern Illinois University, Springfield, USA
Access this book
Other ways to access
Table of contents (81 papers)
-
Neurotoxic Drugs, Transgenic Animals, and Aging Primates as Models of AD Treatment
-
- Lea Oron, Vladimir Dubovik, Mira Perlman, Larisa Novitsky, Daniel M. Michaelson
Pages 395-401
-
Use of Imaging Techniques (SPECT, MRI, PET) to Monitor the Effect of Drugs in AD Treatment
-
Front Matter
Pages 403-403
-
-
- Bertrand Tavitian, Sabina Pappata, Antoinette Jobert, Christian Crouzel, Luigi Di Giamberardino, Anna M. Planas
Pages 413-416
-
- Philippe Robert, Michel Benoit, Guy Darcourt, Octave Migneco, Jacques Darcourt, Francoise Bussiere
Pages 417-423
-
- Randolph W. Parks, Carter S. Young, Robert F. Rippey, Valerie Danz, Cathy Vohs, Jane R. Matthews et al.
Pages 424-427
-
Clinical Testing of Efficacy of New Drugs in AD
-
Front Matter
Pages 429-429
-
- Serge Gauthier, Howard Feldman, Erich Mohr
Pages 431-435
-
-
- Richard C. Mohs, Deborah B. Marin, Cynthia R. Green, Kenneth L. Davis
Pages 441-443
-
- Ronald F. Zec, Edward S. Landreth, Eden Bird, Rosemary B. Harris, Randall Robbs, Stephen J. Markwell et al.
Pages 444-449
-
- Dennis Q. McManus, Rosemary B. Harris, Larry F. Hughes
Pages 450-455
-
Socio-Economic Aspects in the Treatment of Alzheimer’s Disease
-
Front Matter
Pages 457-457
-
- Marco Trabucchi, Stefano Govoni, Angelo Bianchetti
Pages 459-463
-
-
- E. J. Souêtre, W. Qing, I. Vigoureux, H. Lozet, J. F. Dartigues, L. Lacomblez et al.
Pages 470-478
-
Alzheimer Disease Treatment: The Future
-
Front Matter
Pages 479-479
-
-
- Lars-Olof Wahlund, Richard F. Cowburn, Bengt Winblad, Lars Lannfelt
Pages 485-492
-
About this book
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.