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Increased Lipid Peroxidation Precedes Amyloid Plaque Formation in an Animal Model of Alzheimer Amyloidosis
Open accessAbstract
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.
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“All of these markers of OS have been described as an early alteration in the AD brain, and this concept has been used in the past to support the ‘oxidative stress hypothesis’ in the pathogenesis of AD [20,28,29,30].”
From Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery (2021) · cites this paper as [20]
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“Past and recent studies have demonstrated that oxidative damage is not only an early event in the pathogenesis of AD, occurring before the onset of clinical symptoms but also a factor contributing to the disease progression [17,18,19,20,21].”
From Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery (2021) · cites this paper as [20]
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“The pioneering studies, conducted to validate the early changes of products of oxidative damage, found in specimens of AD patients, in a transgenic mouse model (Tg2576) of AD amyloidosis, dated back more than 20 years [20,124].”
From Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery (2021) · cites this paper as [20]
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“Indeed, the recent demonstration of rare Ab plaques as well as scant amounts of formic acid-extractable Ab in 8-month-old Tg2576 mouse brains prompts cautious interpretation of our data with respect to whether LPO precedes or is linked to the initial stages of AD-like amyloidosis in Tg2576 mice ( Kawarabayashi et al.,…”
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Metadata
- Authors
- Praticò, D., Uryu, K., Leight, S., Trojanoswki, J. Q., & Lee, V. M.-Y.
- Affiliations
- University of Pennsylvania (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2001-06-15
- Volume
- 21
- Issue
- 12
- Pages
- 4183-4187
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6762743
- OpenAlex
- W1954454186
- Cited by
- 777
- References
- 24
- Citations by year
- 2026: 4 · 2025: 15 · 2024: 17 · 2023: 29 · 2022: 19 · 2021: 32 · 2020: 23 · 2019: 27 · 2018: 16 · 2017: 24 · 2016: 24 · 2015: 28 · 2014: 32 · 2013: 37 · 2012: 48
- FWCI
- 22.76
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- National Institutes of Health (AG-11542)
- National Institute on Aging (P01AG011542, AG 11542)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- lipid peroxidation, isoprostanes, amyloid-beta, amyloid plaques, Alzheimer's disease, Tg2576 mice, oxidative stress, Aβ40, amyloid-beta 42, brain oxidative damage, pathogenesis
- MeSH terms
- Aging, Alzheimer Disease, Amyloidosis, Animals, Brain, Cerebellum, Cerebral Cortex, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, Female, Hippocampus, Male, Mice, Transgenic, Peptide Fragments, Lipid Peroxidation, Dinoprost, Amyloid beta-Peptides, Mice, Plaque, Amyloid
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