A vulnerable subtype of dopaminergic neurons drives early motor deficits in Parkinson's disease

A new bioRxiv preprint led by the Costa Lab at the Allen Institute and Columbia University, with collaborators at the Alves da Silva Lab (Champalimaud Foundation) and the Quantitative Imaging Group, identifies a molecularly defined subtype of dopaminergic neurons in the ventral substantia nigra that is selectively vulnerable in Parkinson's disease and drives early motor symptoms.

In Parkinson's disease, dopaminergic neurons (DANs) in the midbrain gradually degenerate, with ventral substantia nigra pars compacta (SNc) neurons exhibiting greater vulnerability. The study identifies a Sox6+ subtype of ventral SNc DANs that is preferentially affected and links the loss of this subtype to motor deficits that emerge before widespread degeneration.

The Quantitative Imaging Group contributed quantitative imaging and analysis methods supporting the molecular and anatomical characterization of dopaminergic neuron subtypes across mouse models of Parkinson's disease.

A vulnerable subtype of dopaminergic neurons drives early motor deficits in Parkinson's disease. Fushiki A, Ng D, Lewis ZR, Yadav A, Saraiva T, Hammond LA, Wirblich C, Tasic B, Menon V, Alves da Silva J, Costa RM. bioRxiv. 2026.

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