Main description:

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.

Contents:

Part 1 Conceptual Framework 1. The definition of precision medicine in neurodegenerative disorders and the one disease-many-diseases tension 2. Models of precision medicine for neurodegeneration 3. Pathology vs pathogenesis: Rationale and pitfalls in the clinicopathology model of neurodegeneration 4. Mixed pathology as a rule, not exception: Time to reconsider disease nosology? 5. Neurodegenerative disorders: From clinicopathology convergence to systems biology divergence 6. The emergence of genotypic divergence and future precision medicine applications 7. Lessons from other fields of medicine, Part 1: Breast cancer 8. Lessons from other fields of medicine, Part 2: Cystic fibrosis 9. Lessons learned from evolving frameworks in adult glioblastoma

Part 2 Pitfalls in Definitions, Cohorts, and Measures of Progression 10. Finding the falsification threshold of the toxic proteinopathy hypothesis in neurodegeneration 11. The theoretical problems of "prodrome" and "phenoconversion" in neurodegeneration 12. The dilemma between milestones of progression vs. clinical scales in Parkinson disease 13. Biomarkers of diagnosis, prognosis, pathogenesis, response to therapy: Convergence or divergence? Lessons from Alzheimer Disease and synucleinopathies 14. Challenges in the study of individuals at risk for Parkinson disease 15. The challenging quest of neuroimaging: From clinical to molecular-based subtyping of Parkinson disease and atypical parkinsonisms