Serum and Cerebrospinal Fluid Uric Acid Levels in Lewy Body Disorders: Associations with Disease Occurrence and Amyloid-β Pathway

Article type: Research Article

Authors: Maetzler, Walter^{a; b; c; *} | Stapf, Anne Kathrin^{a; b} | Schulte, Claudia^{a; b} | Hauser, Ann-Kathrin^{a; b} | Lerche, Stefanie^{a; b} | Wurster, Isabel^{a; b} | Schleicher, Erwin^d | Melms, Arthur^e | Berg, Daniela^{a; b}

Affiliations: [a] Center of Neurology, Department of Neurodegeneration and Hertie Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany | [b] German Center for Neurodegenerative Diseases, University of Tuebingen, Tuebingen, Germany | [c] Department of Geriatric Rehabilitation, Robert-Bosch-Hospital, Stuttgart, Germany | [d] Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, University of Tuebingen, Tuebingen, Germany | [e] Department of General Neurology, Hertie Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany

Correspondence: [*] Correspondence to: Walter Maetzler, MD, Department of Neurodegeneration, Hertie Institute for Clinical Brain Research, University of Tuebingen, Hoppe Seyler-Strasse 3, 72076 Tuebingen, Germany. Tel.: +49 7071 2982047; Fax: +49 7071 294490; E-mail: walter.maetzler@uni-tuebingen.de.

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.

Keywords: Amyloid-β, oxidative stress, Parkinson's disease, single nucleotide polymorphism, uric acid

DOI: 10.3233/JAD-2011-110587

Journal: Journal of Alzheimer's Disease, vol. 27, no. 1, pp. 119-126, 2011