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Peripheral F 2 ‐isoprostanes and F 4 ‐neuroprostanes are not increased in Alzheimer's disease
Author(s) -
Montine Thomas J.,
Quinn Joseph F.,
Milatovic Dejan,
Silbert Lisa C.,
Dang Theresa,
Sanchez Stephanie,
Terry Erin,
Roberts L. Jackson,
Kaye Jeffrey A.,
Morrow Jason D.
Publication year - 2002
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.10272
Subject(s) - cerebrospinal fluid , urine , central nervous system , disease , metabolite , medicine , alzheimer's disease , central nervous system disease , oxidative stress , pathology , endocrinology
Quantitative biomarkers of oxidative damage, such as the F 2 ‐isoprostanes (IsoPs) and F 4 ‐neuroprostanes (F 4 ‐NeuroPs), may be useful in assessing progression and response to therapeutics in patients with Alzheimer's disease. F 2 ‐IsoPs and F 4 ‐NeuroPs are reproducibly increased in brain and cerebrospinal fluid of Alzheimer's disease patients; however, results in blood and urine have been conflicting. We tested the hypothesis that F 2 ‐IsoPs and F 4 ‐NeuroPs in plasma or urine quantitatively reflect oxidative damage to the central nervous system. Our results showed that urine levels of F 2 ‐IsoPs or their major metabolite were not significantly different between 56 Alzheimer's disease patients and 34 controls. In addition, urine and cerebrospinal fluid F 2 ‐IsoP levels in 32 Alzheimer's disease patients did not correlate. Supporting these conclusions, elevated rat cerebral F 2 ‐IsoPs and F 4 ‐NeuroPs after systemic exposure to kainic acid were not associated with a significant change in their plasma or urine levels. These results show that plasma and urine F 2 ‐IsoPs and F 4 ‐NeuroPs do not accurately reflect central nervous system levels of these biomarkers and are not reproducibly elevated in body fluids outside of central nervous system in Alzheimer's disease patients. These results should guide the organization of clinical trials now being planned for patients with Alzheimer's disease.