- •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.
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.
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- LRRK2 at the crossroad of aging and Parkinson’s disease.Genes. 2021; 12: 505
- Parkinson’s disease: etiology, neuropathology, and pathogenesis.Exon Publ. 2018; : 3-26
- Serum neurofilament light chain levels reflect cortical neurodegeneration in de novo Parkinson's disease.Parkinsonism Relat Disord. 2020; 74: 43-49
- The cell biology of LRRK2 in Parkinson's disease.Mol Cell Biol. 2021; 41: e00660-e00720
- Serum neurofilament dynamics predicts cognitive progression in de novo parkinson’s disease.J Parkinsons Dis. 2021; 11: 1117-1127
- Genome-wide survival study identifies a novel synaptic locus and polygenic score for cognitive progression in Parkinson’s disease.Nat Genet. 2021; 53: 787-793
- The genetics of Parkinson disease.Ageing Res Rev. 2018; 42: 72-85
Monfrini E, Fonzo AD. Leucine-rich repeat kinase (LRRK2) genetics and Parkinson’s disease. Leucine-rich repeat kinase 2 (LRRK2). 2017:3-30.
- Genomewide association studies of LRRK2 modifiers of Parkinson's disease.Ann Neurol. 2021; 90: 76-88
- Sequential screening nominates the Parkinson's disease associated kinase LRRK2 as a regulator of Clathrin-mediated endocytosis.Neurobiol Dis. 2020; 141: 104948
- Validation of serum neurofilament light chain as a biomarker of Parkinson's disease progression.Mov Disord. 2020; 35: 1999-2008
- Serum NFL discriminates Parkinson disease from atypical parkinsonisms.Neurology. 2019; 92: e1479-e1486
- CSF and blood biomarkers for Parkinson's disease.Lancet Neurol. 2019; 18: 573-586
- Increased neurofilament light chain blood levels in neurodegenerative neurological diseases.PLoS One. 2013; 8: e75091
- Different clinical contexts of use of blood neurofilament light chain protein in the spectrum of neurodegenerative diseases.Mol Neurobiol. 2020; 57: 4667-4691
- Neurofilament light chain as a biomarker in neurological disorders.J Neurol Neurosurg Psychiatry. 2019; 90: 870-881
- Contributions of central and systemic inflammation to the pathophysiology of Parkinson's disease.Neuropharmacology. 2012; 62: 2154-2168
- Monogenetic forms of Parkinson’s disease-bridging the gap between genetics and biomarkers.Front Aging Neurosci. 2022; : 14
- What have we learned from cerebrospinal fluid studies about biomarkers for detecting LRRK2 Parkinson’s disease patients and healthy subjects with Parkinson’s-associated LRRK2 mutations?.J Parkinsons Dis. 2019; 9: 467-488
- Biochemical markers for severity and risk in GBA and LRRK2 Parkinson’s disease.J Neurol. 2021; 268: 1517-1525
- Neurofilaments as biomarkers in neurological disorders.Nat Rev Neurol. 2018; 14: 577-589
- MDS clinical diagnostic criteria for Parkinson's disease.Mov Disord. 2015; 30: 1591-1601
- Neurofilament light protein in CSF and blood is associated with neurodegeneration and disease severity in Huntington’s disease R6/2 mice.Sci Rep. 2017; 7: 14114
- Are genetic and idiopathic forms of Parkinson's disease the same disease?.J Neurochem. 2020; 152: 515-522
- DaT-SPECT assessment depicts dopamine depletion among asymptomatic G2019S LRRK2 mutation carriers.PLoS One. 2017; 12: e0175424
- Diagnostic value of cerebrospinal fluid neurofilament light protein in neurology: a systematic review and meta-analysis.JAMA Neurol. 2019; 76: 1035
- Association between longitudinal plasma neurofilament light and neurodegeneration in patients with Alzheimer disease.JAMA Neurol. 2019; 76: 791-799
- LRRK2 in Parkinson disease: challenges of clinical trials.Nat Rev Neurol. 2020; 16: 97-107
- Glial and neuronal markers in cerebrospinal fluid predict progression in multiple sclerosis.Mult Scler. 2015; 21: 550-561
- Blood-based NfL: A biomarker for differential diagnosis of parkinsonian disorder.Neurology. 2017; 88: 930-937
- LRRK2 links genetic and sporadic Parkinson's disease.Biochem Soc Trans. 2019; 47: 651-661
- LRRK2 activation in idiopathic Parkinson's disease.Sci Transl Med. 2018; 10
- LRRK2 and idiopathic Parkinson's disease.Trends Neurosci. 2022; 45: 224-236
- Progression in the LRRK2-asssociated Parkinson disease population.JAMA Neurol. 2018; 75: 312-319
- LRRK2 G2019S Parkinson's disease with more benign phenotype than idiopathic.Acta Neurol Scand. 2018; 138: 425-431
- CSF NFL in a longitudinally assessed PD cohort: age effects and cognitive trajectories.Mov Disord. 2020; 35: 1138-1144
- Association of cerebrospinal fluid neurofilament light protein levels with cognition in patients with dementia, motor neuron disease, and movement disorders.JAMA Neurol. 2019; 76: 318
- Motor and nonmotor heterogeneity of LRRK2-related and idiopathic Parkinson's disease.Mov Disord. 2016; 31: 1192-1202
Accepted: January 31, 2023
Received: November 3, 2022
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