• Günter U Höglinger, Charles H Adler, Daniela Berg, Christine Klein, Tiago F Outeiro, Werner Poewe, Ronald Postuma, A Jon Stoessl, and Anthony E Lang.
• Department of Neurology, University Hospital, Ludwig-Maximilians-University (LMU) and German Center for Neurodegenerative Diseases, Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
• Lancet Neurol. 2024 Feb 1; 23 (2): 191204191-204.

AbstractWith the hope that disease-modifying treatments could target the molecular basis of Parkinson's disease, even before the onset of symptoms, we propose a biologically based classification. Our classification acknowledges the complexity and heterogeneity of the disease by use of a three-component system (SynNeurGe): presence or absence of pathological α-synuclein (S) in tissues or CSF; evidence of underlying neurodegeneration (N) defined by neuroimaging procedures; and documentation of pathogenic gene variants (G) that cause or strongly predispose to Parkinson's disease. These three components are linked to a clinical component (C), defined either by a single high-specificity clinical feature or by multiple lower-specificity clinical features. The use of a biological classification will enable advances in both basic and clinical research, and move the field closer to the precision medicine required to develop disease-modifying therapies. We emphasise the initial application of these criteria exclusively for research. We acknowledge its ethical implications, its limitations, and the need for prospective validation in future studies.Copyright © 2024 Elsevier Ltd. All rights reserved.

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