This two-volume work contains the full text of the oral and poster presentations and the general discussion at the round table discussion of the Second International Conference on Alzheimer's and Parkinson's Diseases: Basic and Therapeutic Strategies, held at the Kyoto Park Hotel in Kyoto, Japan, on November 6-10, 1989. The First Conference was held at the Aviya Sonesta Hotel in Eilat, Israel, on March 24-27, 1985. The record of this First Conference was published by Plenum Press in 1986 as Volume 29 in Advances in Behavioral Biology, under the title "Alzheimer's and Parkinson's Diseases: Strategies for Research and Development." We are happy that the comprehensive texts of the oral and poster presentations of the Second Conference could again be published within the framework of this series. Since the First Conference in 1985, rapid progress has been made in both basic and 'therapeutic aspects of these diseases. About 700 scientists from allover the world participated in the Second Conference, and 300 papers were presented in oral and poster sessions. Many people and organizations have helped to organize this multi disciplinary international conference and hence have contributed to the scientific quality of these two volumes. We thank the members of the organizing committee, the organizations that provided financial support, and the contributing scientists for their enthusiastic participation. These two volumes follow the same publishing philosophy as the volume derived from the First Conference. They span a broad spectrum of topics and bridge preclinical and clinical concepts related to these diseases.
Table of ContentsPlenary Lectures.- Functional Principles Implied in Neurological Symptoms.- The Neurobiology of Alzheimer’s Disease.- Role of Brain Monoamines and Other Neurotransmitters in Normal and Pathological Aging.- Amyloid.- Molecular Genetics of Alzheimer’s Disease.- Proteins and Proteolysis in the Pathogenesis of Alzheimer’s Disease.- Amyloid ? Protein Precursors Having Proteinase Inhibitor Regions Are Highly Expressed in Alzheimer’s Disease Brains.- Differential Expression of Three Types of Amyloid Protein Precursor mRNA in Alzheimer’s Disease Brain.- Protease Inhibitor and Cholinergic System in Alzheimer’s Disease.- Structure and Expression of mRNA for the Mouse Homolog of Alzheimer Amyloid Beta Protein Precursor.- Molecular Cloning and Structural Analysis of the Human Amyloid ? Protein Precursor Gene.- Protease Nexin 1 Immunoreactivity in Senile Plaques in Alzheimer Disease and Aged Brain.- Monoclonal Antibodies Against Senile Plaque Amyloid in Alzheimer’s Disease.- Identification of Putative Amyloid A4-Splitting Enzymes with Two Endopeptidases Widely Distributed in Mammalian Cells.- Proteolytic Processing of ?-Protein Precursor-Related Synthetic Peptides.- Degeneration of Neuronal Processes in Rats Induced by the Protease Inhibitor Leupeptin.- ?1-Antichymotrypsin Influences the Survival of Neurons.- Evidence for a Neuronal Origin of Senile Plaques in Down’s Syndrome Brains.- Serum Amyloid P Immunoreactivity in Cortical Tangles, Plaques and Vessels in Alzheimer’s Disease: Implications for Dysfunction of the Blood-Brain Barrier ?.- Monoamine Oxidase B Activity in Senile Plaque.- Light and Electron Microscopic Observations of Diffuse Plaque and Its Related Conditions.- ?-Amyloid Plaques and Dementia: An Immunohistochemical Study.- Diagnosis of Cerebral Amyloid Angiopathy with Cerebral Hemorrhage by Enzyme-Linked Immunosorbent Assay (ELISA) of Cystatin C in Cerebrospinal Fluid.- Cystatin C (?-Trace) and ?-Protein Coexist in the Cerebral Amyloid Angiopathy Causing Cerebral Hemorrhage and Consequential Vascular Dementia.- The Neuronal Breakdown-1 (Alzheimer).- The Regulation of Cytoskeletal Elements in Differentiating Human Neuroblastoma and Rat Pheochromocytoma PC-12 Cells.- Some Findings on Intermediate Filaments in Alzheimer’s Disease.- A Unifying Hypothesis on the Etiology of Alzheimer’s Disease.- Abnormal Phospholipid Metabolism in Neurodegenerative Diseases: Elevations in Glycerophosphocholine and Glycerophosphoethanolamine Levels in Brain of Alzheimer’s Disease but Not in Down Syndrome Patients.- Alterations in Catecholamine and Peptide Neurons in the Locus Coeruleus in Dementias of Alzheimer’s and Parkinson’s Disease.- The Role of Neuronal Membranes Deterioration in the Pathogenesis of Alzheimer’s Disease: An Ultrastructural Perspective.- Experimental Synaptic Degeneration as a Model for the Pathogenesis of Alzheimer’s Disease: Monoclonal Antibodies and a Protein Kinase Inhibitor Block Synapse Formation and Maintenance between Cultured CNS Neurons.- Pathobiochemical Aspects of Parkinson’s Disease and Dementia of Alzheimer Type.- Characterization of Alzheimer Neurofibrillary Tangle (NFT) Epitopes and the Binding Site for the Regulatory Subunit (RII) of cAMP-Dependent Protein Kinase II in Human Microtubule-Associated Protein 2 (MAP-2).- Identification and Characterization of Modified Forms of Tau in Brains with Alzheimer’s Disease.- Phosphorylation of Tau Protein with a Novel Tau Protein Kinase Forming Paired Helical Filament Epitopes on Tau.- Aberration of Vimentin Array in Fibroblast from Familial Alzheimer’s Disease.- Regional Phospholipid Profile of Alzheimer’s Brain: 31P and Proton NMR Spectroscopic Studies of Membrane Lipid Extracts.- Age-Related Changes in the Rate and Composition of the Slow Axonal Transport.- Astroglial Gene Expression in the Hippocampus following Partial Deafferentation in the Rat and in Alzheimer’s Disease.- Blood-Brain Barrier Disturbance in Patients with Alzheimer’s Disease Is Related to Vascular Factors.- An Early Change of Neurofibrillary Tangle Formation.- Monoclonal Antibodies against Paired Helical Filament in Alzheimer’s Disease and Parkinsonism-Dementia Complex of Guam.- Neuronal Breakdown-2 (Parkinson).- Patterns of Vulnerability of Mesostriatal Neurons.- Complex I Deficiency in Parkinson’s Disease and MPTP-Induced Experimental Parkinsonism.- Biochemical Reactions Leading to Parkinsonian Symptoms Elicited by MPTP.- Enzymological Aspects of the Actions of the Parkinsonism-Inducing Neurotoxin MPTP.- Biochemical Studies on Predisposition to Parkinson’s Disease.- Parkinsonism Produced by an Endogenous Substance, Tetrahydroisoquinoline, in Monkeys and Mice.- Tetrahydroisoquinoline Alkaloids in Neurodegenerative Disorders Influence of Drug Treatment.- Chronic L-Dopa Therapy in Parkinson’s Disease: Can It Accelerate Degeneration of Nigrostriatal Dopaminergic Neurons ?.- Iron-Melanin Interaction in Substantia Nigra as the Neurotoxic Component of Parkinson’s Disease.- Dopamine Immunocytochemistry in the Nigrostriatal System of Pre- and Postnatal Mice.- The Effects of N-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP) Administration to Maternal Mice on the Catecholamine System in the Brain of Postnatal Mice.- Mitochondrial Abnormalities in the Nigral Neurons of Crab-Eating Monkeys with Experimental Parkinsonism.- L-Dopa-Induced Facilitation of Dopamine Release Via Presynaptic ?-Adrenoceptors in Striatal Slices from MPTP-Treated C57BL Mice: Evaluation of the Action of L-Dopa in Animal Model for Parkinsonism.- Functional Alterations in Striatal Cholinergic and Striato-Nigral GABA-Ergic Neurons following 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP) Administration.- Hemiparkinsonism in Monkeys after Unilateral Striatum Infusion of 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP).- Cyclosporin A Enhances Neurotoxicity of N-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP) in Mice.- Effects of Various Drugs on Behavior and Striatal Dopamine Contents in MPTP-Treated Mice Exposed to Stress.- Acute Effects of 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP) on Body Temperature of Various Strains of Mice.- Effect of MPP+ and TIQ on Cultured Rat Midbrain Dopaminergic Neurons.- Assay System for Neurotoxicants Causing Parkinson’s Disease: 1-Methyl-4-Phenylpyridinium Ion (MPP+) Inhibits Survival of Cultured Neurons from Substantia Nigra of Fetal Monkey (Macaca fascicularis).- The Effect of Tetrahydroisoquinoline on the Mitochondrial Respiration.- Detection of Tetrahydroisoquinoline, a Parkinsonism-Related Compound, in Parkinsonian Brains and Foods by Gas Chromatography-Mass Spectrometry.- Biosynthesis of N-Methylisoquinolinium Ion, a Potent Inhibitor of Catecholamine Metabolism, from 1,2,3,4-Tetrahydroisoquinoline through N-Methyl-1,2,3,4-Tetrahydroisoquinoline in Human Brain.- Importance of 1-Methyltetrahydroisoquinoline (1MeTIQ) in Parkinson’s Disease.- Formation of a Novel and Neurotoxic Tetrahydroisoquinoline Derivative, 1,3-Dimethyltetrahydroisoquinoline (1,3DiMeTIQ), a Condensation Product of Amphetamines and Acetaldehyde in Vivo.- Tryptophan Metabolites in Parkinson’s Brain.- A Parallel Relationship between Parkinson’s Disease and an Excess of S-Adenosylmethionine-Dependent Biological Methylation in the Brain.- Dopa and Dopamine Cause the Destruction of Cultured Nerve Cells in the Presence of Iron: Possible Mechanism of the Nigral Degeneration in Parkinson’s Disease.- Food-Derived Heterocyclic Amines as Potent Inhibitors of Catecholamine Metabolism.- Pathology and Histology.- Senile Changes in the Human Olfactory Bulbs.- Large Neurons in the Neostriatum and Basal Nucleus of Meynert: Simultaneous Decrease in Alzheimer’s Disease.- A Comparison of “Pure” Alzheimer’s Disease and Alzheimer’s Disease Plus Vascular Lesions (Mixed Dementia) in the Elderly.- Choline Acetyltransferase and Substance P Level in Alzheimer’s Disease and Multi-Infarct Dementia.- A Study on Postmortem Changes in Vasopressin mRNA in Rat Brain Using a Non-Isotopic Method.- Topographical Distribution, Fine Structure of Component Fibrils, and Immunoreactivity of Neuronal Inclusions in Alzheimer’s, Parkinson’s, and Pick’s Diseases.- Neuronal Loss in the Substantia Nigra and Ventral Tegmental Area in Parkinson’s Disease and Alzheimer’s Disease.- Characteristics of Reactive Microglia in Alzheimer’s and Parkinson’s Disease Brain Tissue.- Alzheimer Parkinson Disease Spectrum and Diffuse Lewy Body Disease.- Acetylcholinesterase Histochemical Changes in the Cerebral Cortex of Alzheimer’s Disease.- Basement Membrane Components in Alzheimer’s Disease.- Regulation of Cerebral Cortical and Hippocampal Blood Flow by Cholinergic Fibers Originating in the Nucleus Basalis of Meynert and Septal Complex.- Immune System Reaction to Model Lesions of Rat Brain.- Computer-Aided Quantitative Analysis of the Distribution of Catecholamine-Containing Fibers in the Primate Prefrontal Cortex.- Nigrostriatal Loop Disruption in Parkinson’s Disease and Striatonigral Degeneration.- Immunocytochemical Studies of Substance P and Met-Enkephalin in the Globus Pallidus of Progressive Supranuclear Palsy.- Heterogeneous Distribution of L-Dopa Immunoreactivity in Dopaminergic Neurons of the Rat Midbrain.- Transmitter.- Cholinergic Systems in Alzheimer’s Disease, Parkinson’s Disease and Progressive Supranuclear Palsy.- Neurochemical Aspects of Parkinson’s Disease and the Dementing Brain Disorders: Relation to Brain Ageing.- Neuropharmacology and Functional Anatomy of the Basal Ganglia: Experimental Models for Parkinson’s and Alzheimer’s Disease.- Neurotransmitter Changes in Alzheimer-Type Dementia and Therapeutic Strategies.- In Vitro Experimental Approach for Determination of the Central Cholinergie Neuronal Activity.- Pharmacological Profile of Brain Glucose Utilization Obtained by Monitoring of Lactate Release in Vivo under the Free Moving Condition.- Behavioral and Neurochemical Evaluation of Stroke-Prone Spontaneously Hypertensive Rats for Vascular Dementia-Animal Model.- Acetylcholinesterase of Cerebral Microvessels Changes in Alzheimer’s Disease.- Genes of Human Catecholamine-Synthesizing Enzymes.- Gene Activity and Neurodegeneration in the Extrapyramidal System: A Progress Report on Molecular and Morphological Correlates.- Analysis of Dopamine and Neuropeptides in 6-OHDA-Lesioned Rats.- Enhancement of in Vivo Dopamine Release from the Rat Striatum by 6R-L-Erythro-5,6,7,8-Tetrahydrobiopterin as Studied by Brain Dialysis.- Preparation of Antigen and Antibody to 3-Methoxy-4-Hydroxyphenyl Glycol (MHPG).- Study of Central Putative Neurotransmitters in Rodent Models of Parkinsonism.- Possible Factors Responsible for Adverse Effects of Long-Term L-Dopa Therapy: Simultaneous Determinations of Dopamine Parameters in Rats.- Generating and Controlling Multiparameter Data Bases for Biochemical Correlates of Disorders.- NEUBA ® A Multicolumn, Multidetector Liquid Chromatograph with Electrochemical Detection for Use in the Identification and Determination of Neurochemicals and Related Species.- Examination of Central Nervous System Effects of Amphetamine Using NEUBA ®.- Application of Multi-Dimensional Liquid Chromatography (NEUBA ® to the Determination of Neuronal Changes in an Organism.- Patterns of Tyrosine and Tryptophan Metabolites in Controls and Various Degenerative Disorders.- Receptor.- Dementia in Parkinson’s Disease and Central Cholinergic Function.- Subtypes of Nicotinic Receptors in Human Cortex: Selective Changes in Alzheimer Disease.- Alterations in Muscarinic Cholinergic Receptors and the Second Messenger System in the Cerebral Cortex in Alzheimer-Type Dementia.- Expression of Nicotinic Acetylcholine Receptor mRNA in the Rat Cerebral Cortex after Lesioning of the Nucleus Basalis Magnocellularis.- Studies of Central Nervous System Cholinergic Receptors in Alzheimer’s Disease (AD).- Cerebellar Excitatory Amino Acid Binding Sites Are Differentially Altered in Alzheimer’s Disease.- Pre- and Postsynaptic Cortical Glutamatergic Binding Sites in Alzheimer’s Disease.- Reduced N-Methyl-D-Aspartate (NMDA) Receptor-Ion Channel Complex in Alzheimer’s Disease Frontal Cortex.- The Influence of Priming on the Behavioral Expression of Dopamine Receptor Supersensitivity in Basal Ganglia.- M1 Receptors Stimulate Dopamine Release Via Protein Kinase C in the Striatum of Freely Moving Rat Studied by Brain Dialysis.- Effect of MPTP on Dopamine D2 Receptors in the Aging Mouse Striatum.- Age-Dependent Effects of 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP) in the Rat.- More Rapid Development of Supersensitivity of D-2 Receptors than D-1 Receptors as Examined by Rotational Behavior.- Features of the Dopaminergic Neurotoxicity of Methamphetamine: A Comparison with MPTP.- Alteration of [3H]Ins(1,4,5)P3 and [3H]PDBu Binding Sites in Brains of Patients with Parkinson’s Disease and Multiple System Atrophy.- NGF and Physiology.- The Mechanism of Action of Nerve Growth Factor.- Nerve Growth Factor Promotes Survival of Cultured Cholinergic Neurons from Nucleus Basalis of Meynert of 2-Week-Old Rats.- Alterations in Nerve Growth Factor Receptor Containing Neurons in Parkinson’s Disease.- A Striatal-Derived DA Neuron Growth Factor: Implication in Parkinson’s Disease.- Co-Localization of Cholinergic and GABAergic Traits in in Vitro Septohippocampal Neurons from Developing Rats.- A Hippocampal Cell Line Expresses a Membrane-Associated Cholinergic Trophic Activity Not Attributable to Nerve Growth Factor.- Interleukin-6 as a Neurotrophic Factor for Promoting Survival of Septal Cholinergic Neurons and Mesencephalic Catecholaminergic Neurons from Postnatal Rats.- Distribution of NGF Receptors in Control and Alzheimer’s Disease Basal Forebrain.- Trophic Effects of Hippocampus Cell Membrane Fragments on Cultured Medial Septal Cholinergic Neurons.- Changes in Basal Forebrain Cholinergic Systems Following Excitotoxic Cell Death in the Hippocampus and Cerebral Neocortex.- Interleukin-3 Promotes Neurite Outgrowth and Elevates Choline Acetyltransferase Activity.- Memory Impairment in Rats Induced by an Active Fragment of Nerve Growth Factor Antibody.- Brain’s Calculating Principle.- Screening for Psychotherapeutic Chemicals by Analysis of Conscious Activity in the Mouse.- Regulation of Neocortical Electrical Activity by Cholinergic and Noradrenergic Systems.- Ascending Cholinergic and Monoaminergic Systems in the Brainstem: Do They Constitute a Reticular Activating System ?.- Role of the Medial Limbic System in the Memory Process: A Hypothesis Based on a Radioactive 2-Deoxyglucose Study.- Effect of Magnetism on Learning Function.- Model.- Morphological Changes of the Brain in Senescence Accelerated Mouse (SAM)-P/8, a Newly Developed Memory-Deficient Strain.- Age-Related Changes in Blood-Brain Barrier (BBB).- Effect of Aging on NADPH-Diaphorase Neurons in Laterodorsal Tegmental Nucleus and Striatum of Senescence Accelerated Mouse (SAM).- Senescence-Accelerated Mouse SAM-P/8 Shows Spontaneous Age-Related Impairment of Ability of Acquisition of Learning and Memory: An Animal Model of Disturbances in Recent Memory with Aging.- An Experimental Animal Model for the Study of Cholinergic and Serotonergic Neuronal Activity in Aging Brain.- Aging Effects on Schedule-Control Discrimination Learning Test in Aged Rats as a Model of Alzheimer’s Disease.- Effect of the Basal Forebrain Lesions on Memory and Learning Performance in Mice.- Effects of Destruction of Nucleus Basalis Meynert on Operant Study and Neurotransmitters in Rats.- Characteristic of Learning Deficit Induced by Ibotenic Acid Lesion of the Frontal Cortex Related with the Nucleus Basalis of Meynert in Rats.- A New Animal Model of Alzheimer’s Disease by Selective Destruction of the Cholinergic Neurons in the Basal Forebrain.- Impairment of Avoidance Behavior Produced by Destruction of the Cholinergic Projection from the Pedunculopontine Nucleus to the Medial Thalamus.- Impaired Spatial Learning in Rats With a Trimethyltin-Induced Hippocampal Lesion and the Effect of Fetal Septal Grafting on the Impairment.- Some Effects of CNS Cholinergic Neurons on Memory and ACh Release.- Carbon Monoxide (CO)-Induced Delayed Amnesia and Delayed Neuronal Death.- Graft.- Modifications in the Levels of Antibodies in the CSF of Parkinson’s Disease Patients following Adrenal-to-Brain Transplantation.- Autotransplantation of Parasympathetic Cholinergic Neurons into Alzheimer Model Rat Brain.- Use of MPTP-Hemiparkinsonian (HP) Monkeys to Evaluate Efficacy of Tissue Implants as a Treatment for Parkinson’s Disease.- Autotransplantation of Sympathetic Ganglion into the Brain of Parkinsonian Monkey.- Long-Term Survival of Grafted Cells, Dopamine Synthesis/Release, Receptor Activity, and Functional Recovery after Grafting of Fetal Nigral Cells in Model Animals of Hemi-Parkinson’s Disease.- Intra-Accumbens Dopaminergic Grafts Restore Methamphetamine-Induced Locomotor Hyperactivity Response and the Release and Metabolism of Dopamine in Rats Having 6-OHDA Lesions in the Ventral Tegmental Area.- Investigation of MHC Antigens on Neural Graft in Mouse Parkinson’s Models.