Degenerative parkinsonian syndromes: what the neuropathologist can tell the clinician

The definitive diagnosis of Parkinson’s disease, and indeed, of most neurodegenerative diseases, is based on the postmortem examination. Neuropathology continues to be the authoritative approach until reliable clinical and biological markers are found, as well as it helps to understand how clinical symptoms, imaging, and biological findings correlate with the topography, the type and the severity of the lesions. In this thesis, I review the neuropathological characteristics and clinicopathological correlations in Parkinson’s disease and other related disorders, also including the particularities of genetically determined conditions. I explain how the continued stream of novel molecular genetic and neuropathological data on neurodegenerative disorders makes the relationship between phenotype, genotype and pathology more and more complex. I address the clinical relevance and the challenges of mixed neurodegenerative pathologies in elderly patients. I present our review paper on Lewy body disorders. I demonstrate the clinicopathological confrontation in an unusual case of corticobasal degeneration. I present our large autopsy study on the etiologies and diagnostic accuracy of parkinsonism as well as the neuropathological findings in a cohort of patients with Parkinson’s disease related dementia. Finally, I report on our work on the neuropathological correlates of parkinsonian symptoms in pure Alzheimer’s disease. My future plans include the organization of a brain donation program for patients with neurodegenerative disorders. A cohort of prospectively followed patients with subsequent postmortem examination and brain banking would be an ideal setting for clinicopathological correlations, for validation of diverse biomarkers, and for basic research purposes