Correlation of key markers of oxidative stress and inflammation in human cerebrospinal fluid across a wide age range with diet, lifestyle and psychosocial factors.
Oxidative stress (OS) refers to the pathological state in which the production of reactive oxygen species is increased above the body’s antioxidant defence capacity. Functional damage with subsequent cell death occurs as a consequence of the oxidisation of fundamental cellular components such as proteins, lipids and nuclear material (i.e. DNA).1 Accumulating evidence supports the role of OS in the pathogenesis of a number of neurodegenerative diseases.
The brain is particularly vulnerable to oxidative stress as it uses a large amount of oxygen and glucose for energy, generating large quantities of reactive oxygen species (ROS),3 and advanced glycation end products (AGE’s).4 The brain also contains a high concentration of polyunsaturated fatty acids, which are particularly sensitive to oxidative damage.3 Moreover, throughout life the brain is exposed to excitatory amino acids such as glutamate and other excitatory neurotransmitters, that, when present in excess, induce excitotoxicity and high levels of OS.
A number of studies have demonstrated that the cerebrospinal fluid (CSF) and brain tissue of patients with Alzheimer’s disease (AD) is associated with increased levels of OS markers. 5-8 However two important questions remain unanswered: 1) At what stage of life does this oxidative damage begin and 2) What are the factors that influence this rise in OS?
- Quantitate the levels of key biochemical markers of a) psychosocial stress b) antioxidant capacity c) oxidative stress (OS) and d) inflammation; in human cerebrospinal fluid (CSF) and serum across a wide range of human age groups.
- Correlate levels of OS measured in CSF and serum with; a) the age of the subject, b) existing clinical condition(s) including medications, c) diet and lifestyle, d) depression anxiety and stress scores, e) mental activity score, f) current mental state.
- Compare levels of OS between CSF and plasma.
- Gilgun-Sherki Y, Melamed E, Offen D. Oxidative stress induced-neurodegenerative diseases: the need for antioxidants that penetrate the blood brain barrier. Neuropharmacology. 2001;40:959–975.
- Lovell MA, Markesbery WR. Ratio of 8-hydroxyguanine in intact DNA to free 8-hydroxyguanine is increased in Alzheimer disease ventricular cerebrospinal fluid. Arch Neurol. 2001;58:392-396.
- Montine TJ. Biomarkers of oxidative damage and inflammation in Alzheimer’s disease. Biomarkers in Medicine. 2010;4:27-36.
- Vitek M P, Bhattacharya K, Glendening J M, Stopa E, Vlassara H, Bucala R, Manogue K, and Cerami A. Advanced glycation end products contribute to amyloidosis in Alzheimer disease. Proc. Nati. Acad. Sci. 1994;91:4766-4770.
- Butterfield DA, Lauderbacklipid CM. Peroxidation and protein oxidation in alzheimer’s disease brain: potential causes and consequences involving amyloid _-peptide-associated free radical oxidative stress. Free Radical Biology & Medicine.2002;32(11):1050–1060.
- Song WL, Lawson JA, Reilly D, Rokach J, Chang CT, Giasson B, and FitzGerald GA. Neurofurans, novel indices of oxidant stress derived from docosahexaenoic acid. J Biol Chem. 2008;283: 6–16.
- Nourooz-Zadeh J, Liu EH, Yhlen B, Anggard EE, Halliwell B. F4-isoprostanes as specific markers of docosahexaenoic acid peroxidation in Alzheimers Disease. J Neurochem. 1999;72:734-740.
- Montine TJ, Markesbery WR, Morrow JD, Roberts LJ. Cerebrospinal fluid F2 isoprostane levels are increased in Alzheimer’s disease. Ann. Neurol.1998; 44:410–413.