Aging-related increase in oxidative stress correlates with developmental pattern of beta-secretase activity and beta-amyloid plaque formation in transgenic Tg2576 mice with Alzheimer-like pathology

Topic: Brain proteins, microglia and lab models

The molecular mechanisms of beta-amyloidogenesis in sporadic Alzheimer's disease are still poorly understood. To reveal whether aging-associated increases in brain oxidative stress and inflammation may trigger onset or progression of beta-amyloid deposition, a transgenic mouse (Tg2576) that express the Swedish double mutation of human amyloid precursor protein (APP) was used as animal model to study the developmental pattern of markers of oxidative stress and APP processing. In Tg2576 mouse brain, cortical levels of soluble beta-amyloid (1-40) and (1-42) steadily increased with age, but significant deposition of fibrillary beta-amyloid in cortical areas did not occur before postnatal age of 10 months.

Key findings

• To reveal whether aging-associated increases in brain oxidative stress and inflammation may trigger onset or progression of beta-amyloid deposition, a transgenic mouse (Tg2576) that express the Swedish double mutation of human amyloid precursor protein (APP) was used as animal model to study the developmental pattern of markers of oxidative stress and APP processing.
• In Tg2576 mouse brain, cortical levels of soluble beta-amyloid (1-40) and (1-42) steadily increased with age, but significant deposition of fibrillary beta-amyloid in cortical areas did not occur before postnatal age of 10 months.
• The slope of increase in cerebral cortical beta-secretase (BACE1) activities in Tg2576 mice between ages of 9 and 13 months was significantly higher as compared to that of the alpha-secretase, while the expression level of BACE1 protein and mRNA did not change with age.
• The activities of superoxide dismutase and glutathione peroxidase in cortical tissue from Tg2576 mice steadily increased from postnatal age 9-12 months.

Why it matters

In a transgenic mouse model, soluble beta-amyloid rose with age and fibrillary deposits appeared only after 10 months, suggesting oxidative stress and inflammation may relate to amyloid deposition. This is animal-model evidence only and does not show that treating oxidative stress prevents or cures Alzheimer's disease in people.

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Study details

• Evidence strengthLow

Read the original

• DOI: 10.1016/j.ijdevneu.2004.07.006
• PubMed: 15465277
• Original source →

May need a subscription OpenAlex found no free copy of the full text (checked 6 Feb 1020), so the publisher may charge for it. The PubMed abstract is free.

@article{apelt2004-15465277,
  author  = {Apelt, J. and Bigl, M. and Wunderlich, P. and Schliebs, R.},
  title   = {{Aging-related increase in oxidative stress correlates with developmental pattern of beta-secretase activity and beta-amyloid plaque formation in transgenic Tg2576 mice with Alzheimer-like pathology}},
  journal = {International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience},
  year    = {2004},
  doi     = {10.1016/j.ijdevneu.2004.07.006},
  pmid    = {15465277},
  url     = {https://doi.org/10.1016/j.ijdevneu.2004.07.006}
}

Studies this one cites

Referenced by this study and also in the alzhub library, so you can read them here.

• Correlative Memory Deficits, Aβ Elevation, and Amyloid Plaques in Transgenic Mice Science · 1996-10-04 · usefulness score 62/100 · Laboratory science
• Inflammation and Alzheimer's disease Neurobiology of Aging · 2000-06-01 · usefulness score 59/100 · Inflammation and the immune system
• Age-related CNS disorder and early death in transgenic FVB/N mice overexpressing Alzheimer amyloid precursor proteins Neuron · 1995-11-01 · usefulness score 49/100 · Risk genes beyond APOE
• Beta-secretase protein and activity are increased in the neocortex in Alzheimer disease Archives of neurology · 2002-09-01 · usefulness score 47/100 · Risk genes beyond APOE
• Ibuprofen effects on Alzheimer pathology and open field activity in APPsw transgenic mice Neurobiology of aging · 2001-11-01 · usefulness score 44/100 · Risk genes beyond APOE
• Causative and susceptibility genes for Alzheimer's disease: a review Brain research bulletin · 2003-06-01 · usefulness score 44/100 · Brain tissue and pathology
• Beta-amyloid-induced glial expression of both pro- and anti-inflammatory cytokines in cerebral cortex of aged transgenic Tg2576 mice with Alzheimer plaque pathology Brain research · 2001-03-01 · usefulness score 43/100 · Risk genes beyond APOE

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