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Diseases

Parkinson's Disease Subtypes: New Insights into Body-First and Brain-First Phenotypes

Strategic Insights

— 1 min read

Researchers have made a significant breakthrough in understanding Parkinson's disease (PD), detailing two distinct phenotypes that develop before motor symptoms appear. The study, conducted by the Karolinska Institute, highlights the importance of recognizing these phenotypes to develop targeted and personalized therapeutic strategies.

Key Takeaways:

  • The study analyzed 910 prodromal and 1120 clinical PD cases over a 12-year period, providing comprehensive longitudinal clinical, imaging, and genetic data.
  • Both prodromal and clinical groups with body-first symptoms exhibited greater motor dysfunction, anxiety, and depression at baseline, as well as worse longitudinal motor progression and attention decline compared to brain-first cases.
  • The body-first and brain-first phenotypes were stable over time and predicted conversion to clinical PD in prodromal cases, with specific genetic profiles associated with each phenotype.
  • The study identified new single nucleotide polymorphisms (SNPs) associated with PD phenotypes, such as TRIM40 and IP6K2, linked to worse motor and cognitive outcomes in prodromal cases.
  • The findings emphasize the importance of personalized medicine in PD, allowing for targeted therapies that address specific pathophysiological mechanisms.
  • researchers involved include Massimiliano Passaretti, Daniel Vereb, Mite Mijalkov, Yu-Wei Chang, Hang Zhao, Blanca Zufiria-Gerboles, Jiawei Sun, Giovanni Volpe, Natalia Rivera, Matteo Bologna, and Joana B. Pereira.

Statistics:

  • 910 prodromal and 1120 clinical PD cases were analyzed over a 12-year period.
  • 67% of prodromal cases exhibited body-first symptoms, while 33% showed brain-first symptoms.
  • Body-first cases showed greater motor dysfunction (24.1%) and anxiety/depression incidence (17.3%) compared to brain-first cases (10.1% and 5.2%, respectively).
  • TRIM40 and IP6K2 SNPs were associated with worse motor and cognitive outcomes in prodromal cases, with a 25.1% and 17.5% increased risk of motor decline, respectively.

Sources:

  • Clinical progression and genetic pathways in body-first and brain-first Parkinson's disease. Molecular Neurodegeneration, 2025,20(1):1-20. (Molecular Neurodegeneration - http://www.molecularneurodegeneration.com/).
  • BMC (publisher) - https://doi-org.sdpl.idm.oclc.org/10.1186/s13024-025-00866-5.

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