Ezio Giacobini - Böcker

This volume reviews the new potential treatments and research in the area of Alzheimer's disease. Special attention is given to international developments in all fields relevant to new drug development. Topics discussed include: progress in the international harmonization of drug development guidelines for dementia drugs; bioethics and law; development of rating instruments; behavioural treatments; and the activities of the Reagan Foundation. The text integrates basic and clinical research findings, and provides evaluation of new approaches to therapy by world leaders in the field. The potential benefit for Alzheimer patients and families resulting from these research programmes, from molecular biology to clinical pharmacology, is reviewed and evaluated.

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.

One of the most impressive advances in the field of neuroscience over the last decade has been the accumulation of data on plasticity and regeneration in the nervous system of mammals. The book represents the contribution of a qroup of neuroscientists to this rapidly expanding field, through a Conference organized by the Institute of Developmental Neuroscience and Aging (IDNA). The meeting was held in Torino, Italy during April 1990 in honor of a great pioneer in the field of Neuroembryology, Professor Guido Filogamo. His introduction of the concept of neuroplasticity has had a significant impact on the study of neurobiology. This volume is divided into six sections, each focusing on one of the subject areas covered during the meeting Molecular and Cellular Aspects of Central and Peripheral Nervous System Development; Hormones,* Growth Factors, Heurotransmi tters, Xenobiotics and Development; In Vivo and in Vitro models of Development; Development and Regulation of Glia; Regeneration; and Aging.