Alzheimer’s disease (AD) is the most common cause of dementia. No effective pharmaceutical agents exist to halt or slow down the disease progression. There is a tremendous imperative to gain a better understanding of the pathogenesis of AD and to develop effective treatments. This book brings together an international team of experts to provide a comprehensive and up-to-date overview of AD. The most current information on several critical aspects of AD are presented, providing the readers with a broad picture of the underlying neuropathology, genetics, proteomics, risk factors, novel biomarkers, and potential interventions. Chapters 1–5 discuss the underlying AD pathogenesis using genomic and proteomic approaches, linking diverse pathways that can lead to complex metabolic dysfunction. Chapter 6 reviews the potential role of trace metals in AD, while Chapter 7 examines the diversity of Aβ species involved in AD pathology. Chapter 8 discusses the contributions of white matter degeneration in AD. Chapter 9 examines the potential intriguing role of the brain-gut-microbiota axis in mediating AD. Chapters 10 and 11 discuss potential biomarkers for AD, such as deficits in ocular exploration and early language impairments, respectively. Chapters 12–15 examine possible novel preventative and/or therapeutic methodologies such as exercise, optimizing depression therapy, and diverse psychosocial interventions. The book will be of value to clinicians and health professionals caring for patients with AD, and will provide a comprehensive and thought-provoking introduction to young investigators interested in translational aspects of the AD and related dementias.

Contents

• Foreword
• Preface
• List of Contributors
• 1. A New Perspective on Alzheimer’s Disease as a Brain Expression of a Complex Metabolic Disorder
  Baruh Polis and Abraham O. Samson.
  • INTRODUCTION
  • EARLY- AND LATE-ONSET AD ARE TWO DIFFERENT ENTITIES
  • LOAD AS A SYSTEMIC METABOLIC DISORDER
  • A CONTRIBUTION OF THE UREA CYCLE AND POLYAMINE METABOLIC PATHWAY IN THE DEVELOPMENT OF AD
  • A PUTATIVE ROLE OF BCCAS IN THE DEVELOPMENT OF AD
  • CONCLUSION
  • REFERENCES
• 2. Gene Ontology: A Resource for Analysis and Interpretation of Alzheimer’s Disease Data
  Barbara Kramarz and Ruth C. Lovering.
  • INTRODUCTION
  • GENE ONTOLOGY
  • CONCLUSION
  • REFERENCES
• 3. Using Proteomics to Understand Alzheimer’s Disease Pathogenesis
  Eleanor Drummond and Thomas Wisniewski.
  • INTRODUCTION
  • THE BENEFITS OF USING PROTEOMICS TO STUDY PROTEIN CHANGES IN AD BRAIN TISSUE
  • AD PROTEOMIC STUDIES USING BULK TISSUE HOMOGENATES
  • THE USE OF PROTEOMICS TO UNDERSTAND SELECTIVE VULNERABILITY IN AD
  • PROTEOMICS OF NEUROPATHOLOGICAL FEATURES PRESENT IN AD
  • PROTEOMICS OF SYNAPTIC FRACTIONS IN AD
  • ANALYSIS OF THE Aβ OR TAU INTERACTOME IN AD
  • CONCLUSION
  • REFERENCES
• 4. Common Proteomic and Genomic Contribution to Ischemic Brain Damage and Alzheimer’s Disease
  Ryszard Pluta, Marzena Ułamek-Kozioł, Sławomir Januszewski, and Stanisław J. Czuczwar.
  • INTRODUCTION
  • AMYLOID STAINING AND BLOOD LEVEL AFTER BRAIN ISCHEMIA
  • TAU PROTEIN STAINING, PHOSPHORYLATION, AND BLOOD LEVEL AFTER BRAIN ISCHEMIA
  • mRNAs ASSOCIATED WITH THE AMYLOID PROTEIN PRECURSOR AFTER BRAIN ISCHEMIA
  • EXPRESSION OF GENES INVOLVED IN THE PRODUCTION OF AMYLOID AFTER BRAIN ISCHEMIA
  • EXPRESSION OF THE TAU PROTEIN GENE IN THE CA1 AREA AFTER BRAIN ISCHEMIA
  • EXPRESSION OF GENES INVOLVED IN THE DIRECT DEATH OF NEURONS AFTER BRAIN ISCHEMIA
  • THE RELATIONSHIP BETWEEN IRON DYSHOMEOSTASIS AND AMYLOIDOGENESIS
  • CONCLUSION
  • REFERENCES
• 5. Contributing Factors of Neurodegeneration in Alzheimer’s Disease
  Breeya Tailor, Alexander Pilozzi, and Xudong Huang.
  • INTRODUCTION
  • AMYLOID PRECURSOR PROTEIN
  • β-SITE OF APP CLEAVING ENZYME 1
  • GENETIC RISK FACTORS OF ALZHEIMER DISEASE PATHOLOGY
  • THE NEUROIMMUNE SYSTEM
  • BLOOD–BRAIN BARRIER
  • METALS
  • CONCLUSION
  • REFERENCES
• 6. The Role of Trace Metals in Alzheimer’s Disease
  Chiara A. De Benedictis, Antonietta Vilella, and Andreas M. Grabrucker.
  • INTRODUCTION
  • METAL INTERACTIONS WITH APP
  • METAL INTERACTIONS WITH AMYLOID-BETA (Aβ)
  • METAL INTERACTIONS WITH TAU
  • OTHER METAL-BINDING PROTEINS AND THEIR ROLE IN AD
  • METAL DETECTION FOR AD DIAGNOSIS
  • METALS HOMEOSTASIS AS A THERAPEUTIC STRATEGY FOR AD
  • CONCLUSIONS AND FUTURE PERSPECTIVES
  • REFERENCES
• 7. N-Terminally Truncated Aβ Peptide Variants in Alzheimer’s Disease
  Oliver Wirths, Silvia Zampar, and Sascha Weggen.
  • INTRODUCTION
  • HETEROGENEITY OF N-TRUNCATED Aβ SPECIES IN AD BRAIN
  • N-TERMINALLY TRUNCATED Aβ SPECIES IN TRANSGENIC MOUSE MODELS OF AD
  • MAJOR N-TERMINAL TRUNCATED Aβ SPECIES DETECTED IN HUMAN BRAIN
  • CONCLUSION
  • REFERENCES
• 8. Insulin Resistance and Oligodendrocyte/Microvascular Endothelial Cell Dysfunction as Mediators of White Matter Degeneration in Alzheimer’s Disease
  Suzanne M. de la Monte and Paula Grammas.
  • INTRODUCTION
  • AD-ASSOCIATED WM PATHOLOGY
  • ASTROCYTES, MICROGLIA, AND OLIGODENDROCYTES
  • BIOCHEMICAL AND CELLULAR BASIS OF WM PATHOLOGY IN AD
  • POTENTIAL ROLE OF OLIGODENDROCYTE DYSFUNCTION AS A MEDIATOR OF WM DEGENERATION
  • VASCULOPATHY, VASCULAR DEGENERATION, AND ISCHEMIC INJURY IN AD
  • INSULIN AND INSULIN-IGF SIGNALING IMPAIRMENTS AS MEDIATORS OF WM GLIAL-VASCULAR DEGENERATION IN AD
  • CONCLUSION
  • REFERENCES
• 9. Relationship between Alzheimer’s Disease and the Human Microbiome
  Yusuke Fujii, Anushka Khasnobish, and Hidetoshi Morita.
  • INTRODUCTION
  • AD AND DIABETES
  • AD AND PERIODONTAL DISEASE
  • AD AND OBESITY
  • MICROBIOTA AND AMYLOID ACCUMULATION
  • EFFECTS OF DAIRY PRODUCTS AND PROBIOTICS IN AD
  • AD AND GUT MICROBIOTA
  • GUT MICROBIOTA AND BEHAVIOR
  • CONCLUSION
  • REFERENCES
• 10. Ocular Exploration in the Diagnosis and Follow-Up of the Alzheimer’s Dementia
  Elena Salobrar-Garcia, Rosa de Hoz, Ana I. Ramírez, Juan J. Salazar, Pilar Rojas, Inés López-Cuenca, Jose Fernández-Albarral, and José M. Ramírez.
  • INTRODUCTION
  • EYE AND BRAIN: SYMBIOTIC RELATIONSHIP
  • VISUAL FUNCTIONAL TESTS IN THE EXPLORATION OF AD
  • OPHTHALMOLOGICAL METHODS FOR RETINAL ANALYSIS
  • FUNCTIONAL CHANGES IN AD
  • STRUCTURAL CHANGES IN AD
  • CHANGES IN THE EARLY AD AND THEIR PROGNOSTIC VALUE IN THE DETECTION AND FOLLOW-UP
  • CONCLUSION
  • REFERENCES
• 11. The Deterioration of Semantic Networks in Alzheimer’s Disease
  Israel Martínez-Nicolás, Juan Carro, Thide E. Llorente, and Juan José García Meilán.
  • INTRODUCTION
  • LANGUAGE IMPAIRMENTS IN ALZHEIMER’S DISEASE
  • SEMANTIC IMPAIRMENTS: PRECLINICAL CHANGES
  • CHARACTERISTICS OF THE DETERIORATION OF THE SEMANTIC NETWORK IN AD
  • DEGRADED NETWORK OR FAILURE TO RETRIEVE?
  • THE ORGANIZATION OF THE SEMANTIC NETWORK
  • CONCLUSION
  • REFERENCES
• 12. Alzheimer’s Disease: Memory Interference and the Role of Exercise
  Lindsay Crawford and Paul D. Loprinzi.
  • INTRODUCTION
  • RISK FACTORS
  • EARLY-ONSET ALZHEIMER’S DISEASE
  • TREATMENT
  • MEMORY
  • EXERCISE AND ALZHEIMER’S DISEASE
  • CONCLUSION
  • REFERENCES
• 13. Sense of Self among Persons with Advanced Dementia
  Astrid Norberg.
  • INTRODUCTION
  • SYMPTOMS OF DEMENTIA
  • SELFHOOD
  • PERSONS WITH ADVANCED DEMENTIA
  • SPIRITUAL AND CONSOLING CARE AT THE END OF LIFE
  • CONCLUSION
  • REFERENCES
• 14. Depression in Alzheimer’s Disease: The Roles of Cholinergic and Serotonergic Systems
  Enver Ahmet Demir, Okan Tutuk, Hatice Dogan, and Cemil Tumer.
  • INTRODUCTION
  • HOW DO WE RECOGNIZE DEPRESSION?
  • COGNITIVE DYSFUNCTION MAY LOOK ALIKE DEPRESSION
  • THE COINCIDENCE OF DEPRESSION AND ALZHEIMER’S DISEASE
  • WHAT DOES LIE BEHIND COINCIDING ALZHEIMER’S DISEASE AND DEPRESSION?
  • CONCLUSION
  • REFERENCES
• 15. A Collaborative Approach to Treatment of Alzheimer’s Disease from a Psychological Perspective
  Anna Maria Jadwiga Wegierek, Katarzyna Lesniak, Shan Patel, and Yuliya Bogdanovskaya.
  • INTRODUCTION
  • WHAT IS NEUROPSYCHOLOGY?
  • NEUROPSYCHOLOGICAL TESTING FOR POSSIBLE OR PROBABLE AD
  • DEPRESSION AND AD
  • WHAT DO NEUROPSYCHOLOGISTS HAVE TO OFFER MEDICAL DOCTORS AND HOW IMPORTANT IS THEIR COLLABORATION
  • THE ROLE OF ALCOHOL CONSUMPTION IN DEMENTIA
  • AD AND DECISION-MAKING CAPACITY
  • AD AND OTHER MENTAL HEALTH PROBLEMS
  • AD AND TECHNOLOGY
  • AD AND MARIJUANA USE
  • AD AND THE N-648
  • CONCLUSION
  • REFERENCES

Alzheimer’s Disease

ISBN: 978-0-6468096-8-7

DOI: http://dx.doi.org/10.15586/alzheimersdisease.2019

Edited by

Thomas Wisniewski, MD, New York University Alzheimer’s Disease Center, New York University School of Medicine, New York, USA

Published by

Codon Publications

Brisbane, Australia

Copyright© 2019 Codon Publications

Copyright of individual chapters belongs to the respective authors. The authors grant unrestricted publishing and distribution rights to the publisher. The electronic versions of the chapters are published under Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). https://creativecommons.org/licenses/by-nc/4.0/. Users are allowed to share and adapt the chapters for any non-commercial purposes as long as the authors and the publisher are explicitly identified and properly acknowledged as the original source. The book in its entirety is subject to copyright by the publisher. The reproduction, modification, republication and display of the book in its entirety, in any form, by anyone, for commercial purposes are strictly prohibited without the written consent of the publisher.

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The views and opinions expressed in this book are believed to be accurate at the time of publication. The publisher, editors or authors cannot be held responsible or liable for any errors, omissions or consequences arising from the use of the information contained in this book. The publisher makes no warranty, implicit or explicit, with respect to the contents of this book, or its use.

First Published in November 2019

Printed in Australia