title: CSF Nrf2 and HSPA8 in Parkinson's disease patients with and without LRRK2 gene mutations.
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.
authors.affiliation: 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.
authors.forename: David A
authors.initials: DA
authors.lastname: Loeffler
authors.affiliation: Neurology Research Laboratory, Department of Neurology, Beaumont Hospital-Royal Oak, Beaumont Health, 3601 West Thirteen Mile Road, Royal Oak, MI, 48073, USA.
authors.forename: Lynnae M
authors.initials: LM
authors.lastname: Smith
authors.affiliation: Department of Biostatistics, Beaumont Hospital-Royal Oak, Beaumont Health, Royal Oak, MI, USA.
authors.forename: Mary P
authors.initials: MP
authors.lastname: Coffey
authors.affiliation: Department of Neurology, St. Olav's Hospital, Trondheim, Norway.
authors.forename: Jan O
authors.initials: JO
authors.lastname: Aasly
authors.affiliation: Department of Neurology, Henry Ford West Bloomfield Hospital, West Bloomfield, MI, USA.|Department of Neurology, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Peter A
authors.initials: PA
authors.lastname: LeWitt
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000134:cerebrospinal fluid; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D050883:HSC70 Heat-Shock Proteins / Q000134:cerebrospinal fluid*; D006579:Heterozygote; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D051267:NF-E2-Related Factor 2 / Q000134:cerebrospinal fluid*; D010300:Parkinson Disease / Q000134:cerebrospinal fluid* / Q000235:genetics*
chemical_list: D015415:Biomarkers; D050883:HSC70 Heat-Shock Proteins; C494371:HSPA8 protein, human; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
keywords: Biomarkers; Cerebrospinal fluid; HSPA8; LRRK2; Nrf2; Parkinson’s disease