Remarkable increase in the concentration of 8‐hydroxyguanosine in cerebrospinal fluid from patients with Alzheimer's disease

Abstract

To investigate the possible role of oxidative RNA damage in the pathogenesis of Alzheimer's disease (AD), the concentrations of the oxidative stress marker 8-hydroxyguanosine (8-OHG) were measured in the cerebrospinal fluid (CSF) and the serum of patients with AD and control subjects. The concentration of 8-OHG in CSF in AD patients was approximately fivefold that in controls (P Ͻ 0.001). The concentration of 8-OHG in CSF decreased significantly with the duration of illness (r s ϭ Ϫ0.48, P Ͻ 0.05) and the progression of cognitive dysfunctions (r s ϭ 0.67, P Ͻ 0.01). However, the concentration of 8-OHG in CSF showed no correlation with that in serum in both the controls and AD patients. In addition, the concentration of 8-OHG in serum was not significantly altered in AD patients compared to that in controls, suggesting that the 8-OHG concentrations in the CSF do not reflect those in serum and may be probably reflect those in brain tissue. These in vivo findings suggest a possible role of 8-OHG and increased oxidative RNA damage in the early stage of the development of AD.

Free Radicals: Properties, Sources, Targets, and Their Implication in Various Diseases

“…Indeed, RNA is subjected to more oxidative damage than DNA in humans [77]. 7, 8-dihydro-8-oxoguanosine (8-oxoG) is the most extensively studied RNA damage product and its levels are raised in various pathological conditions like Alzheimer's disease [78], Parkinson's disease [79], atherosclerosis [80], hemochromastosis [81] and myopathies [82].…”

Oxidative RNA Damage and Neurodegeneration

“…In addition to the brain, significantly increased levels of the oxidized RNA nucleoside, 8-OHG, have been identified in cerebrospinal fluid collected from patients with AD and PD [56][57][58] as well as in serum of PD patients [57], which indicates that 8-OHG is a possible biomarker of the diseases. As we describe in the following section,…”

A rapid and sensitive method for quantitation of nucleosides in human urine using liquid chromatography/mass spectrometry with direct urine injection

“…[1][2][3][4][5] Various methods have been developed for quantifying modified nucleosides, based on an enzyme-linked immunosorbent assay (ELISA), 6,7 32 P-post-labelling, 8 capillary electrophoresis, 9,10 HPLC with photodiode array detection 11,12 or ECD, 13 and GC/MS. [14][15][16] However, GC/MS analysis faced additional problems in the hydrolysis and derivatization steps.…”