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Biochemical markers for severity and risk in GBA and LRRK2 Parkinson’s disease

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Abstract

Background

The phenotype of Parkinson’s disease (PD) is variable with mutations in genes such as LRRK2 and GBA explaining part of this heterogeneity. Additional genetic and environmental factors contribute to disease variability.

Objective

To assess the association between biochemical markers, PD severity and probability score for prodromal PD, among GBA and LRRK2 mutation carriers.

Methods

Levels of uric acid, vitamin D, C-reactive protein, microalbumin/creatinine ratio (ACR), white blood count (WBC), hemoglobin, platelets, neutrophil/lymphocyte ratio and estimated glomerular filtration rate (eGFR) were assessed from patients with PD and non-manifesting carriers (NMC) of mutations in GBA and LRRK2, together with disease related questionnaires enabling the construction of the MDS prodromal probability score.

Result

A total of 241 patients with PD: 105 idiopathic PD (iPD), 49 LRRK2-PD and 87 GBA-PD and 412 non-manifesting subjects; 74 LRRK2-NMC, 118 GBA-NMC and 220 non-manifesting non-carriers (NMNC), participated in this study. No significant differences in biochemical measures were detected among patients with PD or non-manifesting carriers. Among GBA-PD patients, worse motor performance was associated with ACR (B = 4.68, 95% CI (1.779–7.559); p = 0.002). The probability score for prodromal PD among all non-manifesting participants was associated with eGFR; NMNC (B = − 0.531 95% CI (− 0.879 to − 0.182); p < 0.001, LRRK2-NMC (B = − 1.014 95% CI (− 1.663 to − 0.366); p < 0.001) and GBA-NMC (B = − 0.686 95% CI (1.300 to − 0.071); p = 0.029).

Conclusion

Sub-clinical renal impairment is associated with increased likelihood for prodromal PD regardless of genetic status. While the mechanism behind this finding needs further elucidation, it suggests that kidney function might play a role in PD pathogenesis.

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Data availability

As this is an industry funded work, anonymized data will be made available with Biogens’ consent.

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Funding

This work was funded by Biogen.

Author information

Authors and Affiliations

  1. Movement Disorder Unit, Laboratory of Early Markers of Neurodegeneration, Neurological Institute, Tel-Aviv Medical Center, 6 Weizmann Street, 64239, Tel-Aviv, Israel

    Avner Thaler, Nurit Omer, Nir Giladi & Tanya Gurevich

  2. Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel

    Avner Thaler, Nurit Omer, Nir Giladi, Tanya Gurevich, Meir Kestenbaum, Avi Orr-Urtreger, Shani Shenhar-Tsarfaty & Anat Mirelman

  3. Sagol School of Neuroscience, Tel-Aviv University, Tel Aviv, Israel

    Avner Thaler, Nir Giladi, Tanya Gurevich & Anat Mirelman

  4. Laboratory of Early Markers of Neurodegeneration, Neurological Institute, Tel-Aviv Medical Center, Tel Aviv, Israel

    Avner Thaler & Anat Mirelman

  5. Genetic Institute, Tel-Aviv Medical Center, Tel Aviv, Israel

    Anat Bar-Shira

  6. Genomic Research Laboratory for Neurodegeneration, Tel-Aviv Medical Center, Tel Aviv, Israel

    Mali Gana-Weisz, Orly Goldstein & Avi Orr-Urtreger

  7. Neurology Department, Meir Medical Center, Kfar Saba, Israel

    Meir Kestenbaum

  8. Biogen Inc., Cambridge, MA, USA

    Jesse M. Cedarbaum

  9. Coeruleus Clinical Sciences LLC, Woodbridge, CT, USA

    Jesse M. Cedarbaum

  10. Department of Internal Medicine “C”, “D”, and “E”, Tel-Aviv Medical Center, Tel-Aviv, Israel

    Shani Shenhar-Tsarfaty

Authors
  1. Avner Thaler
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  2. Nurit Omer
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  3. Nir Giladi
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  6. Mali Gana-Weisz
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  7. Orly Goldstein
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Correspondence to Avner Thaler.

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This work was approved by the Tel-Aviv Medical Center IRB.

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Thaler, A., Omer, N., Giladi, N. et al. Biochemical markers for severity and risk in GBA and LRRK2 Parkinson’s disease. J Neurol 268, 1517–1525 (2021). https://doi.org/10.1007/s00415-020-10325-4

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  • DOI: https://doi.org/10.1007/s00415-020-10325-4

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