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Precision Medicine in Neurodegenerative Disorders
Part I
- 1st Edition, Volume 192 - February 14, 2023
- Editor: Alberto J. Espay
- Language: English
- Hardback ISBN:9 7 8 - 0 - 3 2 3 - 8 5 5 3 8 - 9
- eBook ISBN:9 7 8 - 0 - 3 2 3 - 9 0 0 6 4 - 5
Precision Medicine in Neurodegenerative Disorders, Part One, Volume 192 in the Handbook of Clinical Neurology deals with the "Why" in the approach to slow the progression of a… Read more
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Request a sales quotePrecision Medicine in Neurodegenerative Disorders, Part One, Volume 192 in the Handbook of Clinical Neurology deals with the "Why" in the approach to slow the progression of accelerated brain aging. This volume is intended to provide a scholarly background on the framework, basic science and conceptual pitfalls related to disease-modifying efforts in Parkinson's, Alzheimer's and other neurodegenerative disorders. Among topics covered are different models of precision medicine, the lumping-versus-splitting tension in biomarker development and therapeutics, and the rationale for replacing the convergence of the prevailing autopsy-based nosology of neurodegenerative diseases with the divergence of a systems biology approach to human diseases.
Specific chapters are dedicated to the promise of genetic subtypes and the lessons in disease modification offered by the fields of oncology and cystic fibrosis that can be adapted to the field of neurodegeneration. Matching a biology-correcting therapy with those biologically suitable to benefit from such therapy represents the vision and mission of precision medicine, the highest level of personalized medicine.
- Summarizes theory and research on precision medicine in neurodegenerative disorders
- Covers basic biology, clinical trials and therapeutics
- Includes disease mechanisms, genetic subtypes, and more
Clinical neurologists
- Cover image
- Title page
- Table of Contents
- Copyright
- Handbook of Clinical Neurology 3rd Series
- Foreword
- In Memoriam–Michael Parkinson
- Preface
- Contributors
- Part 1: Conceptual framework
- Chapter 1: The definition of precision medicine in neurodegenerative disorders and the one disease-many diseases tension
- Abstract
- Introduction
- Precision Medicine in the Fields of Oncology vs Neurodegeneration
- One Disease-Many Diseases Tension
- Heterogeneity and the One Disease-Many Diseases Tension
- Moving From Heterogeneity to Precision Medicine and Successful DMT
- Conclusion
- References
- Chapter 2: Models of precision medicine for neurodegeneration
- Abstract
- From the Clinicopathologic Model to Individualized Biological Subtyping
- Is the Model for Symptomatic Treatments Also Helpful for Precision Medicine?
- The Big Picture
- Logistical Implications of the Clinicopathologic Model of Disease
- Why Is There Resistance to Change Away From the Clinicopathology Model?
- Toward a New Model of Precision Medicine
- Conclusions
- Acknowledgment
- Declaration of competing interest
- Disclosures
- Funding
- References
- Chapter 3: Pathology vs pathogenesis: Rationale and pitfalls in the clinicopathology model of neurodegeneration
- Abstract
- Introduction
- Synucleinopathies vs Synucleinopenia
- Tau-Based Disorders: Tauopathies vs Tauopenia
- The Amyloidosis of Alzheimer's Disease
- TDP-43 Proteinopathies and/or TDP-43 Proteinopenia
- Pathology Is Not Pathogenesis
- Conclusions and Future Remarks
- References
- Chapter 4: Mixed pathology as a rule, not exception: Time to reconsider disease nosology
- Abstract
- Introduction
- Neuroinflammation in the PD Brain
- Conclusions
- Acknowledgment
- References
- Chapter 5: Neurodegenerative disorders: From clinicopathology convergence to systems biology divergence
- Abstract
- Introduction
- From GWAS to Disease Pathways
- Systems Medicine for Multifactorial Diseases
- Omics, Multiomics, and Functional Enrichment
- Complex Diseases and Disease Networks
- A Systems Biology View on Parkinson's Disease
- A Systems Biology View on Alzheimer's Disease
- Neurodegeneration Mechanisms From a Systems Biology Point of View
- Concluding Remarks and Perspectives
- References
- Chapter 6: The emergence of genotypic divergence and future precision medicine applications
- Abstract
- A History of Wrong Divergences and Convergences
- Descriptive and Convergent Use of Genetic Variation
- Oligo- and Digenic Genetic Inheritance Causal Quests: First Divergent Steps in Precision Medicine?
- Gain- and Loss-of-Function Genotypes: Truly Divergent Precision Medicine
- Layers of Genotypic Divergence, Penetrance Modifiers, and Somatic Mosaicism
- Are We Approaching the Limit?
- References
- Chapter 7: Lessons from other fields of medicine, Part 1: Breast cancer
- Abstract
- Introduction to Breast Cancer
- Molecular Subtypes and Evolution of Biomarkers
- Surgical Evolution and Multimodal Influences
- Genetics
- Single Gene Prognostic Markers
- Multigene Prognostic Markers
- Future Directions
- Conclusion
- Financial disclosure
- References
- Chapter 8: Lessons from other fields of medicine, Part 2: Cystic fibrosis
- Abstract
- Introduction
- Genetics, Pathophysiology, and Classification
- Novel Therapeutics and Transformation of CF Therapy
- Turning Back the Clock: Pushing the Age Frontier for CFTR Modulator Therapy
- Translational Read-Through and CFTR mRNA Therapies
- CFTR Biomarkers
- Evolution of Cell-Based Assays and CFTR Modulator Theratyping
- Organizational Support
- Future of CF Care and Challenges Ahead
- Conclusions
- References
- Chapter 9: Lessons learned from evolving frameworks in adult glioblastoma
- Abstract
- Introduction
- Medical Imaging of GBMs
- Histopathology
- Genomic Testing, Diagnosis, and Standard of Care
- Clinical Trials and Future Perspectives
- Conclusions
- References
- Further reading
- Part 2: Pitfalls in definitions, cohorts, and measures of progression
- Chapter 10: Finding the falsification threshold of the toxic proteinopathy hypothesis in neurodegeneration
- Abstract
- Background
- Where is the Threshold of Hypothesis Falsification?
- Why and How to Falsify a Hypothesis
- An Alternative to the Toxic Proteinopathy Hypothesis
- Conclusions
- References
- Chapter 11: The theoretical problems of “prodrome” and “phenoconversion” in neurodegeneration
- Abstract
- Introduction
- Suggestions for Future Research
- Conclusions
- Conflict of Interest Disclosures
- References
- Chapter 12: The dilemma between milestones of progression versus clinical scales in Parkinson's disease
- Abstract
- Introduction
- The Natural History of Parkinson's Disease
- Clinical Scales
- Milestones
- Discussion
- Conclusion
- Acknowledgments
- References
- Chapter 13: Biomarkers of diagnosis, prognosis, pathogenesis, response to therapy: Convergence or divergence? Lessons from Alzheimer's disease and synucleinopathies
- Abstract
- Introduction
- Alzheimer's Disease
- Synucleinopathies
- References
- Chapter 14: Challenges in the study of individuals at risk for Parkinson disease
- Abstract
- Introduction
- References
- Chapter 15: The challenging quest of neuroimaging: From clinical to molecular-based subtyping of Parkinson disease and atypical parkinsonisms
- Abstract
- Introduction
- Structural Imaging
- Functional Imaging
- Molecular Imaging
- Future Directions: What Will the Landscape Look Like in 5 Years?
- Acknowledgments
- Conflict of interests
- Conclusions
- References
- Index
- No. of pages: 288
- Language: English
- Edition: 1
- Volume: 192
- Published: February 14, 2023
- Imprint: Elsevier
- Hardback ISBN: 9780323855389
- eBook ISBN: 9780323900645
AE
Alberto J. Espay
Dr. Alberto Espay is Professor and Endowed Chair of the James J. and Joan A. Gardner Center for Parkinson’s disease at the University of Cincinnati. He has published over 300 peer-reviewed research articles and 8 books, including Common Movement Disorders Pitfalls, which received the Highly Commended BMA Medical Book Award in 2013 and Brain Fables, the Hidden History of Neurodegenerative Diseases and a Blueprint to Conquer them, coauthored with Parkinson patient and advocate Benjamin Stecher, selected by the Association of American Publishers for the PROSE Award honoring the best scholarly work in Neuroscience published in 2020. He has served as Chair of the Movement Disorders Section of the American Academy of Neurology, Associate Editor of the Movement Disorders journal, and on the Executive Committee of the Parkinson Study Group. Among other honors, he has received the Cincinnati Business Courier’s Health Care Hero award, the Spanish Society of Neurology’s Cotzias award, and honorary membership in the Mexican Academy of Neurology. He currently serves as President-Elect of the Pan-American Section of the International Parkinson and Movement Disorders Society. With colleagues at the University of Cincinnati, he launched the first biomarker study of aging (CCBPstudy.com), designed to match people with neurodegenerative disorders to available therapies from which they are most biologically suitable to benefit, regardless of their clinical diagnoses.
Affiliations and expertise
Professor of Neurology, Endowed Chair, James J. and Joan A. Gardner Family Center for Parkinson’s Disease and Movement Disorders, University of Cincinnati, Cincinnati, OH, United StatesRead Precision Medicine in Neurodegenerative Disorders on ScienceDirect