Nabizadeh Fardin, Mohamadzadeh Omid, Hosseini Helia, Rasouli Kimia, Afyouni Nazgol Esmalian
Neuroscience Research Group (NRG), Universal Scientific Education and Research Network (USERN), Tehran, Iran; School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Department of Neurosurgery, Tehran University of Medical Science, Tehran, Iran.
J Clin Neurosci. 2023 Apr;110:12-18. doi: 10.1016/j.jocn.2023.01.015. Epub 2023 Feb 11.
Studies revealed that serum neurofilament light chain (NFL) levels not only increase considerably over time in Parkinson's disease (PD) but also have a significant association with disease progression. However, there is no evidence of the level of serum NFL in PD patients with leucine-rich repeat kinase 2 (LRRK2) mutation (LRRK2-PD) which is the most common mutation that causes familial and sporadic PD.
Here we aimed to investigate the difference and longitudinal alteration of the serum level of NFL in LRRK2-PD and idiopathic PD (iPD) patients.
We entered 228 iPD and 103 LRRK2-PD patients and 176 healthy controls (HCs) from PPMI. We compared the level of serum NFL at baseline, six months, one year, two years, three years, and five years visits. Also, we used linear mixed models to assess longitudinal changes of serum NFL over six months, one year, two years, three years, and five years within groups.
We found a significant difference in the level of serum NFL between three groups at baseline, two years, three years, and five years time points. Also, our analysis showed that LRRK2-PD patients had significantly lower serum NFL compared to iPD subjects at baseline. In the longitudinal analysis, there was no significant change in the HCs group over five years. The level of serum NFL was significantly increased after two, three, and five years from baseline in LRRK2-PD patients. Also, we found similar results for iPD subjects after three and five years from baseline.
We can conclude that the overall neurodegeneration might be similar in LRRK2-PD and healthy subjects and lower than the idiopathic form of PD at the early stages, which may disappear in the later stages. Moreover, our findings suggest that the serum NFL might be a more accurate biomarker to distinguish iPD from healthy subjects rather than all PD patients or LRRK2-PD from healthy subjects at the early stages.
研究表明，帕金森病（PD）患者血清神经丝轻链（NFL）水平不仅会随时间显著升高，还与疾病进展显著相关。然而，对于富含亮氨酸重复激酶2（LRRK2）突变的PD患者（LRRK2-PD），尚无血清NFL水平的相关证据，LRRK2突变是导致家族性和散发性PD的最常见突变。
本研究旨在探讨LRRK2-PD和特发性PD（iPD）患者血清NFL水平的差异及纵向变化。
我们纳入了PPMI研究中的228例iPD患者、103例LRRK2-PD患者和176例健康对照（HCs）。我们比较了基线、6个月、1年、2年、3年和5年随访时的血清NFL水平。此外，我们使用线性混合模型评估组内6个月、1年、2年、3年和5年期间血清NFL的纵向变化。
我们发现三组在基线、2年、3年和5年时间点的血清NFL水平存在显著差异。此外，我们的分析表明，基线时LRRK2-PD患者的血清NFL显著低于iPD患者。在纵向分析中，HCs组在5年内无显著变化。LRRK2-PD患者在基线后2年、3年和5年时血清NFL水平显著升高。iPD患者在基线后3年和5年时也得到了类似结果。
我们可以得出结论，LRRK2-PD患者与健康受试者的总体神经退行性变可能相似，且在疾病早期低于特发性PD患者，这种差异在疾病后期可能消失。此外，我们的研究结果表明，血清NFL可能是区分iPD与健康受试者的更准确生物标志物，而不是区分所有PD患者或早期LRRK2-PD与健康受试者的更准确生物标志物。
