Purpose of the review <p>The main unmet need of Parkinson’s disease (PD) is the lack of a therapy able to slow progression. The field is shifting from syndromic diagnosis toward biologically anchored definitions and staging, enabling PD identification before motor onset. In this context, imaging biomarkers provide in vivo measures to identify subtypes, enrich cohorts, and track changes in disease-modifying trials. This review focuses on the role of monoaminergic imaging for preclinical intervention.</p> Recent findings <p>Monoaminergic imaging captures both the core substrate of motor phenoconversion and extranigral mechanisms underlying early non-motor symptoms. Presynaptic dopaminergic imaging remains the most robust marker of conversion risk in prodromal cohorts, while noradrenergic and serotonergic imaging delineate early brainstem and limbic involvement. Peripheral autonomic imaging further extends biomarker coverage, with cardiac sympathetic imaging detecting early extracerebral denervation in prodromal stages.</p> Summary <p>Together, harmonised monoaminergic imaging provides a unifying framework for staging and clinical trial readiness.</p>

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Mapping the Silent Onset of Parkinson’s Disease: Monoamine Imaging in the Era of the Race for Preclinical Intervention

  • Valentina Leta,
  • Valtteri Kaasinen,
  • Bénédicte Ballanger,
  • Roberto Cilia

摘要

Purpose of the review

The main unmet need of Parkinson’s disease (PD) is the lack of a therapy able to slow progression. The field is shifting from syndromic diagnosis toward biologically anchored definitions and staging, enabling PD identification before motor onset. In this context, imaging biomarkers provide in vivo measures to identify subtypes, enrich cohorts, and track changes in disease-modifying trials. This review focuses on the role of monoaminergic imaging for preclinical intervention.

Recent findings

Monoaminergic imaging captures both the core substrate of motor phenoconversion and extranigral mechanisms underlying early non-motor symptoms. Presynaptic dopaminergic imaging remains the most robust marker of conversion risk in prodromal cohorts, while noradrenergic and serotonergic imaging delineate early brainstem and limbic involvement. Peripheral autonomic imaging further extends biomarker coverage, with cardiac sympathetic imaging detecting early extracerebral denervation in prodromal stages.

Summary

Together, harmonised monoaminergic imaging provides a unifying framework for staging and clinical trial readiness.