Parkinson's disease: a broken nosology

Abstract

Parkinson's disease (PD) is a clinical diagnosis. We argue here that if we are to make progress in understanding its underlying pathogenesis, there is a need to have a pathological definition of disease that includes the presence of Lewy bodies and nigral loss in the ventrolateral tier of the pars compacta of the substantia nigra. Using such a definition, there is only one certain and known cause: mutations in the alpha-synuclein gene. However, the phenotype of this one known cause is broader than PD and encompasses Lewy body dementia.