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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 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 disordersCovers basic biology, clinical trials and therapeuticsIncludes disease mechanisms, genetic subtypes, and more
Foreword
In Memoriam–Michael Parkinson
Preface
Contributors
Conceptual framework
The definition of precision medicine in neurodegenerative disorders and the one disease-many diseases tension
Models of precision medicine for neurodegeneration
Pathology vs pathogenesis: Rationale and pitfalls in the clinicopathology model of neurodegeneration
Mixed pathology as a rule, not exception: Time to reconsider disease nosology
Neurodegenerative disorders: From clinicopathology convergence to systems biology divergence
The emergence of genotypic divergence and future precision medicine applications
Lessons from other fields of medicine, Part 1: Breast cancer
Lessons from other fields of medicine, Part 2: Cystic fibrosis
Lessons learned from evolving frameworks in adult glioblastoma
Pitfalls in definitions, cohorts, and measures of progression
Finding the falsification threshold of the toxic proteinopathy hypothesis in neurodegeneration
The theoretical problems of “prodrome” and “phenoconversion” in neurodegeneration
The dilemma between milestones of progression versus clinical scales in Parkinson's disease
Biomarkers of diagnosis, prognosis, pathogenesis, response to therapy: Convergence or divergence? Lessons from Alzheimer's disease and synucleinopathies
Challenges in the study of individuals at risk for Parkinson disease
The challenging quest of neuroimaging: From clinical to molecular-based subtyping of Parkinson disease and atypical parkinsonisms
Index