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CSF Nrf2 and HSPA8 in Parkinson's disease patients with and without LRRK2 gene mutations.
J Neural Transm (Vienna). 2016 Mar; 123(3):179-87.JN

Abstract

Leucine-rich repeat kinase 2 (LRRK2) gene mutations are the most common genetic cause of Parkinson's disease (PD). CSF specimens from LRRK2 + PD patients and healthy LRRK2 mutation carriers are, therefore, useful for biomarker studies. This study examined the hypothesis that differences are present between subjects with sporadic PD (sPD), PD carriers of LRRK2 mutations (LRRK2 + PD), healthy control subjects lacking LRRK2 mutations (CTL), and LRRK2 mutation-carrying healthy controls (LRRK2 + CTL) for CSF concentrations of six potential PD biomarkers. Two of these proteins, nuclear factor (erythroid-derived 2)-like 2 ("Nrf2") and heat shock 70 kDa protein 8 ("HSPA8"), were detected in preliminary ELISAs, then measured in a larger cohort (60 sPD, 10 LRRK2 + PD, 23 CTL, 31 LRRK2 + CTL). No statistically significant differences were found between the groups (Nrf2 p = 0.13, HSPA8 p = 0.21). Nrf2 concentrations in LRRK2 + PD subjects were strongly positively associated with Unified Parkinson's Disease Rating Scale (UPDRS) total and motor scores [Spearman rho = 0.77 (p = 0.012) and 0.83 (p = 0.005)] and negatively associated with Montreal Cognitive Assessment (MoCA) scores (rho = -0.57; p = 0.11). Partial correlation coefficient calculations indicated that disease duration contributed to the associations of Nrf2 levels with UPDRS scores and with MoCA scores in this group. While CSF Nrf2 and HSPA8 do not appear to offer diagnostic biomarkers for PD, the associations between Nrf2 levels and UPDRS scores in LRRK2 + PD patients merit further investigation.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Loeffler DA
Neurology Research Laboratory, Department of Neurology, Beaumont Hospital-Royal Oak, Beaumont Health, 3601 West Thirteen Mile Road, Royal Oak, MI, 48073, USA. DLoeffler@beaumont.edu.
Smith LM
Neurology Research Laboratory, Department of Neurology, Beaumont Hospital-Royal Oak, Beaumont Health, 3601 West Thirteen Mile Road, Royal Oak, MI, 48073, USA.
Coffey MP
Department of Biostatistics, Beaumont Hospital-Royal Oak, Beaumont Health, Royal Oak, MI, USA.
Aasly JO
Department of Neurology, St. Olav's Hospital, Trondheim, Norway.
LeWitt PA
Department of Neurology, Henry Ford West Bloomfield Hospital, West Bloomfield, MI, USA. Department of Neurology, Wayne State University School of Medicine, Detroit, MI, USA.

MeSH

AgedBiomarkersEnzyme-Linked Immunosorbent AssayFemaleGenetic Predisposition to DiseaseHSC70 Heat-Shock ProteinsHeterozygoteHumansLeucine-Rich Repeat Serine-Threonine Protein Kinase-2MaleMiddle AgedMutationNF-E2-Related Factor 2Parkinson Disease

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26526034

Citation

Loeffler, David A., et al. "CSF Nrf2 and HSPA8 in Parkinson's Disease Patients With and Without LRRK2 Gene Mutations." Journal of Neural Transmission (Vienna, Austria : 1996), vol. 123, no. 3, 2016, pp. 179-87.
Loeffler DA, Smith LM, Coffey MP, et al. CSF Nrf2 and HSPA8 in Parkinson's disease patients with and without LRRK2 gene mutations. J Neural Transm (Vienna). 2016;123(3):179-87.
Loeffler, D. A., Smith, L. M., Coffey, M. P., Aasly, J. O., & LeWitt, P. A. (2016). CSF Nrf2 and HSPA8 in Parkinson's disease patients with and without LRRK2 gene mutations. Journal of Neural Transmission (Vienna, Austria : 1996), 123(3), 179-87. https://doi.org/10.1007/s00702-015-1479-0
Loeffler DA, et al. CSF Nrf2 and HSPA8 in Parkinson's Disease Patients With and Without LRRK2 Gene Mutations. J Neural Transm (Vienna). 2016;123(3):179-87. PubMed PMID: 26526034.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CSF Nrf2 and HSPA8 in Parkinson's disease patients with and without LRRK2 gene mutations. AU - Loeffler,David A, AU - Smith,Lynnae M, AU - Coffey,Mary P, AU - Aasly,Jan O, AU - LeWitt,Peter A, Y1 - 2015/11/03/ PY - 2015/05/05/received PY - 2015/10/23/accepted PY - 2015/11/4/entrez PY - 2015/11/4/pubmed PY - 2016/12/15/medline KW - Biomarkers KW - Cerebrospinal fluid KW - HSPA8 KW - LRRK2 KW - Nrf2 KW - Parkinson’s disease SP - 179 EP - 87 JF - Journal of neural transmission (Vienna, Austria : 1996) JO - J Neural Transm (Vienna) VL - 123 IS - 3 N2 - Leucine-rich repeat kinase 2 (LRRK2) gene mutations are the most common genetic cause of Parkinson's disease (PD). CSF specimens from LRRK2 + PD patients and healthy LRRK2 mutation carriers are, therefore, useful for biomarker studies. This study examined the hypothesis that differences are present between subjects with sporadic PD (sPD), PD carriers of LRRK2 mutations (LRRK2 + PD), healthy control subjects lacking LRRK2 mutations (CTL), and LRRK2 mutation-carrying healthy controls (LRRK2 + CTL) for CSF concentrations of six potential PD biomarkers. Two of these proteins, nuclear factor (erythroid-derived 2)-like 2 ("Nrf2") and heat shock 70 kDa protein 8 ("HSPA8"), were detected in preliminary ELISAs, then measured in a larger cohort (60 sPD, 10 LRRK2 + PD, 23 CTL, 31 LRRK2 + CTL). No statistically significant differences were found between the groups (Nrf2 p = 0.13, HSPA8 p = 0.21). Nrf2 concentrations in LRRK2 + PD subjects were strongly positively associated with Unified Parkinson's Disease Rating Scale (UPDRS) total and motor scores [Spearman rho = 0.77 (p = 0.012) and 0.83 (p = 0.005)] and negatively associated with Montreal Cognitive Assessment (MoCA) scores (rho = -0.57; p = 0.11). Partial correlation coefficient calculations indicated that disease duration contributed to the associations of Nrf2 levels with UPDRS scores and with MoCA scores in this group. While CSF Nrf2 and HSPA8 do not appear to offer diagnostic biomarkers for PD, the associations between Nrf2 levels and UPDRS scores in LRRK2 + PD patients merit further investigation. SN - 1435-1463 UR - https://www.unboundmedicine.com/medline/citation/26526034/CSF_Nrf2_and_HSPA8_in_Parkinson's_disease_patients_with_and_without_LRRK2_gene_mutations_ DB - PRIME DP - Unbound Medicine ER -