With the emergence of disease-modifying therapies for Parkinson's disease, reliable longitudinal markers are needed to quantify pathology and demonstrate disease progression. We developed the A53T-AAV rat model of synucleinopathy by combining longitudinal measures over 12 weeks. We first characterized the progression of the motor and dopaminergic deficits. Then, we monitored the disease progression using the [¹⁸F]FMT Positron Emission Tomography (PET) radiotracer.

The nigral injection of A53T-AAV led to an increase in phosphorylated α-synuclein on S129, a progressive accumulation of α-synuclein aggregates, and a decrease of dopaminergic function associated with a deterioration of motor activity. The longitudinal monitoring of A53T-AAV rats with [¹⁸F]FMT PET showed a progressive reduction of the K_c outcome parameter in the caudate putamen from the lesioned side. Interestingly, the progressive reduction in the [¹⁸F]FMT PET signal correlated with defects in the stepping test.

In conclusion, we established a progressive rat model of α-synuclein pathology which monitors the deficit longitudinally using both the [¹⁸F]FMT PET tracer and behavioral parameters, 2 features that have strong relevance for translational approaches.

随着帕金森病疾病缓解疗法的出现，需要可靠的纵向标记来量化病理学和证明疾病进展。我们通过在 12 周内结合纵向测量开发了 A53T-AAV 大鼠突触核蛋白病模型。我们首先描述了运动和多巴胺能缺陷的进展。^{然后，我们使用 [ 18} F]FMT 正电子发射断层扫描 (PET) 放射性示踪剂监测疾病进展。

A53T-AAV 的黑质注射导致 S129 上磷酸化的 α-突触核蛋白增加，α-突触核蛋白聚集体的逐渐积累，以及与运动活动恶化相关的多巴胺能功能下降。^{用[ 18} F]FMT PET对A53T-AAV大鼠进行的纵向监测显示损伤侧尾状壳核中的K _c结果参数逐渐降低。^{有趣的是，[ 18} F]FMT PET 信号的逐渐减少与步进测试中的缺陷相关。

总之，我们建立了 α-突触核蛋白病理学的进行性大鼠模型，该模型使用 [ ¹⁸ F]FMT PET 示踪剂和行为参数纵向监测缺陷，这两个特征与转化方法具有很强的相关性。