title: Serum and cerebrospinal fluid uric acid levels in lewy body disorders: associations with disease occurrence and amyloid-β pathway.
abstract: Recent studies have provided evidence that uric acid (UA), a natural antioxidant, may play a role in the development and progression of Parkinson's disease (PD) and of dementia. In this clinical study we were therefore interested in the role of UA in Lewy body disorders (LBD), which includes Parkinson's disease (PD) and a common form of neurodegenerative dementias, dementia with Lewy bodies (DLB). Ninety-five LBD patients (55 non-demented PD patients, PDND; 20 PD patients with dementia, PDD; and 20 DLB patients) and 76 controls underwent clinical and biochemical analyses including, from a subcohort, cerebrospinal fluid (CSF) analyses, and analysis of three single nucleotide polymorphisms (SNPs) known to be associated with altered serum UA levels. We confirmed previous findings of lowered serum UA levels in LBD patients compared to controls. In CSF, UA levels were significantly higher in PDND patients (median 0.7 mg/dl) compared only to demented LBD patients (0.4 mg/dl; p = 0.03), but not to controls (0.5 mg/dl; p = 0.12). CSF UA levels correlated positively with CSF Aβ42 levels. This correlation was highest in controls (ρ = 0.67), intermediate in PDND (ρ = 0.49), but not observable in demented LBD patients (ρ = 0.10). These findings suggest an involvement of serum UA in LBD occurrence, and an involvement of CSF UA in cognitive decline in LBD, possibly through the Aβ pathway. SNP rs1165205 (SLC17A3) was weakly associated with altered CSF UA levels. Taken together, our results provide first evidence for disease-relevant but potentially distinct roles of UA in the blood and CSF compartment, respectively, in LBD.
authors.affiliation: Center of Neurology, Department of Neurodegeneration and Hertie Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany. walter.maetzler@uni-tuebingen.de
authors.forename: Walter
authors.initials: W
authors.lastname: Maetzler
authors.forename: Anne Kathrin
authors.initials: AK
authors.lastname: Stapf
authors.forename: Claudia
authors.initials: C
authors.lastname: Schulte
authors.forename: Ann-Kathrin
authors.initials: AK
authors.lastname: Hauser
authors.forename: Stefanie
authors.initials: S
authors.lastname: Lerche
authors.forename: Isabel
authors.initials: I
authors.lastname: Wurster
authors.forename: Erwin
authors.initials: E
authors.lastname: Schleicher
authors.forename: Arthur
authors.initials: A
authors.lastname: Melms
authors.forename: Daniela
authors.initials: D
authors.lastname: Berg
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000235:genetics; D003072:Cognition Disorders / Q000209:etiology; D018450:Disease Progression; D005260:Female; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics; D006801:Humans; D020961:Lewy Body Disease / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000150:complications / Q000235:genetics; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D010446:Peptide Fragments / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011955:Receptors, Drug / Q000235:genetics; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters / Q000235:genetics; D014527:Uric Acid / Q000097:blood* / Q000134:cerebrospinal fluid*; D016875:tau Proteins / Q000235:genetics
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D016229:Amyloid beta-Peptides; D051246:Glucose Transport Proteins, Facilitative; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D011955:Receptors, Drug; C578874:SLC12A3 protein, human; C411811:SLC2A9 protein, human; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D014527:Uric Acid