. Serotonergic pathology and disease burden in the premotor and motor phase of A53T α-synuclein parkinsonism: a cross-sectional study. Lancet Neurol. 2019 Aug;18(8):748-759. Epub 2019 Jun 19 PubMed.

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  1. This study complements growing appreciation for the involvement of non-dopaminergic, and extra-nigral, neural circuits in PD pathogenesis, and it extends this concept to early PD stages.

    By studying a cohort of patients with the A53T synuclein mutation, the authors convincingly link evidence for serotonergic dysfunction with synuclein dysfunction, a key pathophysiological player in the mechanisms underlying sporadic PD. Although the patient population is small, the results are convincing and invite further investigations into the involvement of serotonergic systems in PD at early disease stages. 

    Along these lines, there is considerable evidence that the enteric nervous system is involved in PD at the earliest disease stages. Serotonin plays an important role in enteric nervous system function. Future studies should examine whether serotonergic neurons in the ENS are materially involved in this early pathology. In addition to increasing the sample size, the impact of the findings would benefit from histopathological validation, particularly in relation to the Braak staging.

    View all comments by John Woulfe

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