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Increased lipid peroxidation precedes amyloid plaque formation in an animal model of Alzheimer amyloidosis.
J Neurosci 2001; 21(12):4183-7JN

Abstract

Oxidative stress is a key feature in the Alzheimer's disease (AD) brain and manifests as lipid peroxidation (LPO). Isoprostanes (iPs) are specific and sensitive markers of in vivo LPO. To determine whether amyloid beta (Abeta) deposition in vivo is associated with increased LPO, we examined iP levels in a transgenic mouse model (Tg2576) of AD amyloidosis. Urine, plasma, and brain tissues were collected from Tg2576 and littermate wild-type (WT) animals at different time points starting at 4 months of age and continuing until 18 months of age. Levels of urinary 8,12-iso-iPF(2alpha)-VI were higher in Tg2576 than in WT animals as early as 8 months of age and remained this high for the rest of the study. A similar pattern was observed for plasma levels of 8,12-iso-iPF(2alpha)-VI. Homogenates from the cerebral cortex and hippocampus of Tg2576 mice had higher levels of 8,12-iso-iPF(2alpha)-VI than those from WT mice starting at 8 months of age. In contrast, a surge of Abeta 1-40 and 1-42 levels as well as Abeta deposits in Tg2576 mouse brains occurred later, at 12 months of age. A direct correlation was observed between brain 8,12-iso-iPF(2alpha)-VI and Abeta 1-40 and 1-42. Because LPO precedes amyloid plaque formation in Tg2576 mice, this suggests that brain oxidative damage contributes to AD pathogenesis before Abeta accumulation in the AD brain.

Authors+Show Affiliations

Center for Experimental Therapeutics and Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA. domenico@spirit.gcrc.upenn.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11404403

Citation

Praticò, D, et al. "Increased Lipid Peroxidation Precedes Amyloid Plaque Formation in an Animal Model of Alzheimer Amyloidosis." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 21, no. 12, 2001, pp. 4183-7.
Praticò D, Uryu K, Leight S, et al. Increased lipid peroxidation precedes amyloid plaque formation in an animal model of Alzheimer amyloidosis. J Neurosci. 2001;21(12):4183-7.
Praticò, D., Uryu, K., Leight, S., Trojanoswki, J. Q., & Lee, V. M. (2001). Increased lipid peroxidation precedes amyloid plaque formation in an animal model of Alzheimer amyloidosis. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 21(12), pp. 4183-7.
Praticò D, et al. Increased Lipid Peroxidation Precedes Amyloid Plaque Formation in an Animal Model of Alzheimer Amyloidosis. J Neurosci. 2001 Jun 15;21(12):4183-7. PubMed PMID: 11404403.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increased lipid peroxidation precedes amyloid plaque formation in an animal model of Alzheimer amyloidosis. AU - Praticò,D, AU - Uryu,K, AU - Leight,S, AU - Trojanoswki,J Q, AU - Lee,V M, PY - 2001/6/19/pubmed PY - 2001/7/13/medline PY - 2001/6/19/entrez SP - 4183 EP - 7 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J. Neurosci. VL - 21 IS - 12 N2 - Oxidative stress is a key feature in the Alzheimer's disease (AD) brain and manifests as lipid peroxidation (LPO). Isoprostanes (iPs) are specific and sensitive markers of in vivo LPO. To determine whether amyloid beta (Abeta) deposition in vivo is associated with increased LPO, we examined iP levels in a transgenic mouse model (Tg2576) of AD amyloidosis. Urine, plasma, and brain tissues were collected from Tg2576 and littermate wild-type (WT) animals at different time points starting at 4 months of age and continuing until 18 months of age. Levels of urinary 8,12-iso-iPF(2alpha)-VI were higher in Tg2576 than in WT animals as early as 8 months of age and remained this high for the rest of the study. A similar pattern was observed for plasma levels of 8,12-iso-iPF(2alpha)-VI. Homogenates from the cerebral cortex and hippocampus of Tg2576 mice had higher levels of 8,12-iso-iPF(2alpha)-VI than those from WT mice starting at 8 months of age. In contrast, a surge of Abeta 1-40 and 1-42 levels as well as Abeta deposits in Tg2576 mouse brains occurred later, at 12 months of age. A direct correlation was observed between brain 8,12-iso-iPF(2alpha)-VI and Abeta 1-40 and 1-42. Because LPO precedes amyloid plaque formation in Tg2576 mice, this suggests that brain oxidative damage contributes to AD pathogenesis before Abeta accumulation in the AD brain. SN - 1529-2401 UR - https://www.unboundmedicine.com/medline/citation/11404403/Increased_lipid_peroxidation_precedes_amyloid_plaque_formation_in_an_animal_model_of_Alzheimer_amyloidosis_ L2 - http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=11404403 DB - PRIME DP - Unbound Medicine ER -