Increased Lipid Peroxidation Precedes Amyloid Plaque Formation in an Animal Model of Alzheimer Amyloidosis

By D. Praticò, K. Uryu, S. Leight, John Q. Trojanoswki, Virginia M. Y. Lee. Journal of Neuroscience, 2001

799 citations recorded by the source corpus.

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 β (Aβ) deposition in vivois 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-iPF2α-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-iPF2α-VI. Homogenates from the cerebral cortex and hippocampus of Tg2576 mice had higher levels of 8,12-iso-iPF2α-VI than those from WT mice starting at 8 months of age. In contrast, a surge of Aβ 1–40 and 1–42 levels as well as Aβ deposits in Tg2576 mouse brains occurred later, at 12 months of age. A direct correlation was observed between brain 8,12-iso-iPF2α-VI and Aβ 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 Aβ accumulation in the AD brain.

Subfields: Computational Theory and Mathematics, Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/4937d5ca48cde8713ccacfd1138d1ce8e1a92b7f

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Computational Theory and Mathematics

1. M. Beal
2. K. Ashe
3. P. Reddy
4. Barry Halliwell
5. Fusheng Yang
6. Giselle P. Lim
7. O. Ubeda
8. S. Frautschy

In Molecular Biology

1. P. Reddy
2. M. Beal
3. Barry Halliwell
4. M. Mańczak
5. M. Whiteman
6. D. Ofengeim
7. Xiongwei Zhu
8. E. Sanz

In Physiology

1. P. Reddy
2. M. Beal
3. Barry Halliwell
4. M. Mańczak
5. Xiongwei Zhu
6. K. Ashe
7. Michael T. Lin
8. Fusheng Yang

Citations in the corpus

• Amyloid-β overproduction causes abnormal mitochondrial dynamics via differential modulation of mitochondrial fission/fusion proteins (2008, background): “Increased oxidative stress levels have been found in the brains of patients with fAD in Sweden and early in Tg2576 APP transgenic mice (4, 5), suggesting that fAD-associated mutations probably enhance oxidative stress.”
• Mitochondria are a direct site of A beta accumulation in Alzheimer's disease neurons: implications for free radical generation and oxidative damage in disease progression. (2006, result): “Our findings of oxidative damage in Tg2576 mice are in agreement with previous studies of oxidative stress in Tg2576 mice (9,10,22, 34 ,59).”
• The Curry Spice Curcumin Reduces Oxidative Damage and Amyloid Pathology in an Alzheimer Transgenic Mouse (2001, result): “This conclusion is consistent with a recent report in which isoprostanes were elevated in young mice before plaque formation and associated reactive glia (Praticò et al., 2001).”
• Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases (2006, positive): “Oxidative damage also precedes Aβ deposition in transgenic APP mic”
• Oxidative stress and neurodegeneration: where are we now? (2006, background): “Indeed, in mice overexpressing mutant human amyloid precursor protein, brain IP formation preceded amyloid plaque deposition (Pratico et al. 2001) and inhibition of F2-IP formation by a-tocopherol administration delayed plaque formation and cognitive impairment (Sung et al. 2004).”
• Intraneuronal Alzheimer abeta42 accumulates in multivesicular bodies and is associated with synaptic pathology. (2002, methodology): “An increasing number of reports demonstrate behavioral, synaptic, physiological, and oxidative abnormalities months before the appearance of A plaques in FAD transgenic mice that develop AD-like plaque pathology.(5,6,9,12) In Tg2576 mice, which express the human APP Swedish 670/671 FAD mutation,(13)”
• A guide to cell death pathways (2023, positive): “Oxidative stress and lipid peroxidation may be involved in promoting the formation of amyloid-β plaques in animal models of Alzheimer disease 215 .”
• Glial Lipid Droplets and ROS Induced by Mitochondrial Defects Promote Neurodegeneration (2015, positive): “Importantly, signs of oxidative stress precede the neurological signs of neurodegeneration (ND) in disease models (Pratico et al., 2001; Keller et al., 2005; Xie et al., 2013).”
• Measuring reactive species and oxidative damage in vivo and in cell culture: how should you do it and what do the results mean? (2004, background): “…Pratico et al., 2000), and may even be elevated prior to the development of AD (Pratico et al., 2001; 2002), consistent with the view that peroxidation may be an important step in progressive neuronal injury leading to clinically manifested disease (Halliwell, 2001; Pratico et al., 2001; 2002).”
• Docosahexaenoic acid protects from dendritic pathology in an Alzheimer's disease mouse model. (2004, positive): “DHA may be depleted by low dietary intake and losses from lipid peroxidation, which is elevated in AD and Tg2576 mice (Montine et al., 2004; Pratico et al., 2001).”
• Mitochondria take center stage in aging and neurodegeneration (2005, background): “Oxidative damage to lipids precedes -amyloid deposition in AD transgenic mice.(33) Consistent with these observations, administration of antioxidants significantly reduces amyloid plaque deposition in transgenic mouse models of AD.”