TY - JOUR
T1 - F2-isoprostanes in Alzheimer and other neurodegenerative diseases
AU - Montine, Thomas J.
AU - Montine, Kathleen S.
AU - McMahan, Wendy
AU - Markesbery, William R.
AU - Quinn, Joseph F.
AU - Morrow, Jason D.
PY - 2005/1
Y1 - 2005/1
N2 - Increased free radical-mediated injury to brain is proposed to be an integral component of several neurodegenerative diseases, including Alzheimer's disease (AD). Lipid peroxidation is a major outcome of free radical-mediated injury to brain, where it directly damages membranes and generates a number of oxidized products. F2-Isoprostanes (F2-IsoPs), one group of lipid peroxidation products derived from arachidonic acid, are especially useful as in vivo biomarkers of lipid peroxidation. F2-IsoP concentration is selectively increased in diseased regions of brain from patients who died from advanced AD, where pathologic changes include amyloid β (Aβ) amyloidogenesis, neurofibrillary tangle formation, and extensive neuron death. Interestingly, cerebral F2-IsoPs are not reproducibly elevated in aged mouse models of cerebral Aβ amyloidogenesis only. There is broad agreement that increased cerebrospinal fluid (CSF) levels of F2-IsoPs also are present in patients with early AD. Demonstrated applications of quantifying CSF F2-IsoPs have improved laboratory diagnostic accuracy of AD and objective assessment of antioxidant therapeutics. In contrast, quantification of F2-IsoPs in plasma and urine of AD patients has produced conflicting data. These results indicate that brain lipid peroxidation is a potential therapeutic target early in the course of AD, and that CSF F 2-IsoPs may aid in the assessment of antioxidant experimental therapeutics and laboratory diagnosis of AD.
AB - Increased free radical-mediated injury to brain is proposed to be an integral component of several neurodegenerative diseases, including Alzheimer's disease (AD). Lipid peroxidation is a major outcome of free radical-mediated injury to brain, where it directly damages membranes and generates a number of oxidized products. F2-Isoprostanes (F2-IsoPs), one group of lipid peroxidation products derived from arachidonic acid, are especially useful as in vivo biomarkers of lipid peroxidation. F2-IsoP concentration is selectively increased in diseased regions of brain from patients who died from advanced AD, where pathologic changes include amyloid β (Aβ) amyloidogenesis, neurofibrillary tangle formation, and extensive neuron death. Interestingly, cerebral F2-IsoPs are not reproducibly elevated in aged mouse models of cerebral Aβ amyloidogenesis only. There is broad agreement that increased cerebrospinal fluid (CSF) levels of F2-IsoPs also are present in patients with early AD. Demonstrated applications of quantifying CSF F2-IsoPs have improved laboratory diagnostic accuracy of AD and objective assessment of antioxidant therapeutics. In contrast, quantification of F2-IsoPs in plasma and urine of AD patients has produced conflicting data. These results indicate that brain lipid peroxidation is a potential therapeutic target early in the course of AD, and that CSF F 2-IsoPs may aid in the assessment of antioxidant experimental therapeutics and laboratory diagnosis of AD.
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U2 - 10.1089/ars.2005.7.269
DO - 10.1089/ars.2005.7.269
M3 - Review article
C2 - 15650414
AN - SCOPUS:13244271257
SN - 1523-0864
VL - 7
SP - 269
EP - 275
JO - Antioxidants and Redox Signaling
JF - Antioxidants and Redox Signaling
IS - 1-2
ER -