Peripheral F2-isoprostanes and F4-neuroprostanes are not increased in Alzheimer's disease

Thomas J. Montine; Joseph F. Quinn; Dejan Milatovic; Lisa C. Silbert; Theresa Dang; Stephanie Sanchez; Erin Terry; L. Jackson Roberts; Jeffrey A. Kaye; Jason D. Morrow

doi:10.1002/ana.10272

Peripheral F₂-isoprostanes and F₄-neuroprostanes are not increased in Alzheimer's disease

Thomas J. Montine, Joseph F. Quinn, Dejan Milatovic, Lisa C. Silbert, Theresa Dang, Stephanie Sanchez, Erin Terry, L. Jackson Roberts, Jeffrey A. Kaye, Jason D. Morrow

Neurology

Research output: Contribution to journal › Article › peer-review

148 Scopus citations

Abstract

Quantitative biomarkers of oxidative damage, such as the F₂-isoprostanes (IsoPs) and F₄-neuroprostanes (F₄-NeuroPs), may be useful in assessing progression and response to therapeutics in patients with Alzheimer's disease. F₂-IsoPs and F₄-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 F₂-IsoPs and F₄-NeuroPs in plasma or urine quantitatively reflect oxidative damage to the central nervous system. Our results showed that urine levels of F₂-IsoPs or their major metabolite were not significantly different between 56 Alzheimer's disease patients and 34 controls. In addition, urine and cerebrospinal fluid F₂-IsoP levels in 32 Alzheimer's disease patients did not correlate. Supporting these conclusions, elevated rat cerebral F₂-IsoPs and F₄-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 F₂-IsoPs and F₄-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.

Original language	English (US)
Pages (from-to)	175-179
Number of pages	5
Journal	Annals of Neurology
Volume	52
Issue number	2
DOIs	https://doi.org/10.1002/ana.10272
State	Published - 2002

ASJC Scopus subject areas

Neurology
Clinical Neurology

Access to Document

10.1002/ana.10272

Cite this

@article{d08714aff4d34b2797610c1bbf3960c6,

title = "Peripheral F2-isoprostanes and F4-neuroprostanes are not increased in Alzheimer's disease",

abstract = "Quantitative biomarkers of oxidative damage, such as the F2-isoprostanes (IsoPs) and F4-neuroprostanes (F4-NeuroPs), may be useful in assessing progression and response to therapeutics in patients with Alzheimer's disease. F2-IsoPs and F4-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 F2-IsoPs and F4-NeuroPs in plasma or urine quantitatively reflect oxidative damage to the central nervous system. Our results showed that urine levels of F2-IsoPs or their major metabolite were not significantly different between 56 Alzheimer's disease patients and 34 controls. In addition, urine and cerebrospinal fluid F2-IsoP levels in 32 Alzheimer's disease patients did not correlate. Supporting these conclusions, elevated rat cerebral F2-IsoPs and F4-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 F2-IsoPs and F4-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.",

author = "Montine, {Thomas J.} and Quinn, {Joseph F.} and Dejan Milatovic and Silbert, {Lisa C.} and Theresa Dang and Stephanie Sanchez and Erin Terry and Roberts, {L. Jackson} and Kaye, {Jeffrey A.} and Morrow, {Jason D.}",

year = "2002",

doi = "10.1002/ana.10272",

language = "English (US)",

volume = "52",

pages = "175--179",

journal = "Annals of Neurology",

issn = "0364-5134",

publisher = "John Wiley and Sons Inc.",

number = "2",

}

TY - JOUR

T1 - Peripheral F2-isoprostanes and F4-neuroprostanes are not increased in Alzheimer's disease

AU - Montine, Thomas J.

AU - Quinn, Joseph F.

AU - Milatovic, Dejan

AU - Silbert, Lisa C.

AU - Dang, Theresa

AU - Sanchez, Stephanie

AU - Terry, Erin

AU - Roberts, L. Jackson

AU - Kaye, Jeffrey A.

AU - Morrow, Jason D.

PY - 2002

Y1 - 2002

N2 - Quantitative biomarkers of oxidative damage, such as the F2-isoprostanes (IsoPs) and F4-neuroprostanes (F4-NeuroPs), may be useful in assessing progression and response to therapeutics in patients with Alzheimer's disease. F2-IsoPs and F4-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 F2-IsoPs and F4-NeuroPs in plasma or urine quantitatively reflect oxidative damage to the central nervous system. Our results showed that urine levels of F2-IsoPs or their major metabolite were not significantly different between 56 Alzheimer's disease patients and 34 controls. In addition, urine and cerebrospinal fluid F2-IsoP levels in 32 Alzheimer's disease patients did not correlate. Supporting these conclusions, elevated rat cerebral F2-IsoPs and F4-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 F2-IsoPs and F4-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.

AB - Quantitative biomarkers of oxidative damage, such as the F2-isoprostanes (IsoPs) and F4-neuroprostanes (F4-NeuroPs), may be useful in assessing progression and response to therapeutics in patients with Alzheimer's disease. F2-IsoPs and F4-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 F2-IsoPs and F4-NeuroPs in plasma or urine quantitatively reflect oxidative damage to the central nervous system. Our results showed that urine levels of F2-IsoPs or their major metabolite were not significantly different between 56 Alzheimer's disease patients and 34 controls. In addition, urine and cerebrospinal fluid F2-IsoP levels in 32 Alzheimer's disease patients did not correlate. Supporting these conclusions, elevated rat cerebral F2-IsoPs and F4-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 F2-IsoPs and F4-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.

UR - http://www.scopus.com/inward/record.url?scp=0035984342&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035984342&partnerID=8YFLogxK

U2 - 10.1002/ana.10272

DO - 10.1002/ana.10272

M3 - Article

C2 - 12210787

AN - SCOPUS:0035984342

SN - 0364-5134

VL - 52

SP - 175

EP - 179

JO - Annals of Neurology

JF - Annals of Neurology

IS - 2

ER -

Peripheral F₂-isoprostanes and F₄-neuroprostanes are not increased in Alzheimer's disease

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this