Peripheral F2-isoprostanes and F4-neuroprostanes are not increased in Alzheimer's disease.
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.
Montine
Thomas J
TJ
Department of Pathology, Vanderbilt University Medical Center, Nashville, TN 37232, USA. tom.montine@mcmail.vanderbilt.edu
Quinn
Joseph F
JF
Milatovic
Dejan
D
Silbert
Lisa C
LC
Dang
Theresa
T
Sanchez
Stephanie
S
Terry
Erin
E
Roberts
L Jackson
LJ
Kaye
Jeffrey A
JA
Morrow
Jason D
JD
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism* / Q000652:urine; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid / Q000652:urine; D001921:Brain / Q000378:metabolism / Q000473:pathology; D028441:F2-Isoprostanes / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism* / Q000652:urine; D006801:Humans; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values
D015415:Biomarkers; D028441:F2-Isoprostanes; D007608:Kainic Acid