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Purpose <p>We investigated serotonergic and dopaminergic terminal integrity role in <i>PRKN-</i>associated Parkinsonism (PRKN-PD) using [¹¹C]DASB Positron Emission Tomography (PET) and [¹²³I]FP-CIT Single Photon Emission Computerised Tomography (SPECT).</p> Methods <p>Fourteen PRKN-PD patients (mean age 49.70 ± 10.83, disease duration 10.95 ± 7.59 years, H&amp;Y 2.0 ± 0.68), and twelve iPD patients (mean age 65.40 ± 7.48 years, disease duration 5.05 ± 4.50 years, H&amp;Y 2.0 ± 0.93) underwent clinical assessments, 3-Tesla MRI, [<sup>11</sup>C]DASB PET-CT, and [<sup>123</sup>I]FP-CIT SPECT, and compared with previously acquired healthy control (HCs) data. [<sup>11</sup>C]DASB distribution volume ratio (DVR) parametric images were generated and DVR-1 values, equivalent to BP<sub>ND</sub>, sampled from a priori selected regions-of-interest (ROIs) with the posterior cerebellum as reference. [<sup>123</sup>I]FP-CIT images underwent reconstruction and normalization to standard space, and striatal Specific Binding Ratio (SBR) calculated from the eight hottest consecutive slices.</p> Results <p>PRKN-PD patients showed 20.8% to 45.2% [<sup>11</sup>C]DASB BP<sub>ND</sub> loss across several cortical and subcortical ROIs compared to HCs (<i>p</i> ≤ 0.01). After adjusting for age and disease duration, no differences in [<sup>11</sup>C]DASB BP<sub>ND</sub> were observed between PRKN-PD and iPD. In PRKN-PD, higher [<sup>11</sup>C]DASB BP<sub>ND</sub> in the raphe, brainstem, ventral striatum, and amygdala, correlated with higher scores on the Non-Motor Symptoms Scale (<i>p</i> &lt; 0.05). Higher [<sup>11</sup>C]DASB BP<sub>ND</sub> in the caudate and putamen correlated with higher scores on the Beck Depression Inventory II scale (<i>p</i> &lt; 0.05). No correlation was detected between [<sup>11</sup>C]DASB BP<sub>ND</sub> and [<sup>123</sup>I]FP-CIT SBR in the caudate and putamen.</p> Conclusions <p>PRKN-PD is characterized by widespread serotonergic dysfunction, which is independent of dopaminergic degeneration and linked to key non-motor symptoms, particularly depression. These findings provide novel insights into the pathophysiology of PRKN-PD.</p>

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Loss of serotonergic function in carriers of PRKN mutations: a [11C]DASB PET study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月29日

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  • Edoardo Rosario de Natale,
  • Heather Wilson,
  • Joji P. Verghese,
  • Eoin Mulroy,
  • Savvas Antoniadis,
  • Alana Terry,
  • Francesco Cavallieri,
  • Micol Avenali,
  • Pasquale Nigro,
  • Varvara Valotassiou,
  • Eugenii A. Rabiner,
  • Stephen Mullin,
  • Nicola Tambasco,
  • Maria Teresa Pellecchia,
  • Georgia Xiromerisiou,
  • Vicky L. Marshall,
  • Esther Sammler,
  • Enza Maria Valente,
  • Franco Valzania,
  • Kailash P. Bhatia,
  • Marios Politis

摘要

Purpose

We investigated serotonergic and dopaminergic terminal integrity role in PRKN-associated Parkinsonism (PRKN-PD) using [¹¹C]DASB Positron Emission Tomography (PET) and [¹²³I]FP-CIT Single Photon Emission Computerised Tomography (SPECT).

Methods

Fourteen PRKN-PD patients (mean age 49.70 ± 10.83, disease duration 10.95 ± 7.59 years, H&Y 2.0 ± 0.68), and twelve iPD patients (mean age 65.40 ± 7.48 years, disease duration 5.05 ± 4.50 years, H&Y 2.0 ± 0.93) underwent clinical assessments, 3-Tesla MRI, [11C]DASB PET-CT, and [123I]FP-CIT SPECT, and compared with previously acquired healthy control (HCs) data. [11C]DASB distribution volume ratio (DVR) parametric images were generated and DVR-1 values, equivalent to BPND, sampled from a priori selected regions-of-interest (ROIs) with the posterior cerebellum as reference. [123I]FP-CIT images underwent reconstruction and normalization to standard space, and striatal Specific Binding Ratio (SBR) calculated from the eight hottest consecutive slices.

Results

PRKN-PD patients showed 20.8% to 45.2% [11C]DASB BPND loss across several cortical and subcortical ROIs compared to HCs (p ≤ 0.01). After adjusting for age and disease duration, no differences in [11C]DASB BPND were observed between PRKN-PD and iPD. In PRKN-PD, higher [11C]DASB BPND in the raphe, brainstem, ventral striatum, and amygdala, correlated with higher scores on the Non-Motor Symptoms Scale (p < 0.05). Higher [11C]DASB BPND in the caudate and putamen correlated with higher scores on the Beck Depression Inventory II scale (p < 0.05). No correlation was detected between [11C]DASB BPND and [123I]FP-CIT SBR in the caudate and putamen.

Conclusions

PRKN-PD is characterized by widespread serotonergic dysfunction, which is independent of dopaminergic degeneration and linked to key non-motor symptoms, particularly depression. These findings provide novel insights into the pathophysiology of PRKN-PD.