Chronic antioxidant therapy reduces oxidative stress in a mouse model of Alzheimer's disease

Sandra L. Siedlak, Gemma Casadesus, Kate M. Webber, Miguel Pappolla, Craig S. Atwood, Mark A. Smith, George Perry

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Oxidative modifications are a hallmark of oxidative imbalance in the brains of individuals with Alzheimer's, Parkinson's and prion diseases and their respective animal models. While the causes of oxidative stress are relatively well-documented, the effects of chronically reducing oxidative stress on cognition, pathology and biochemistry require further clarification. To address this, young and aged control and amyloid-β protein precursor-over-expressing mice were fed a diet with added R-alpha lipoic acid for 10 months to determine the effect of chronic antioxidant administration on the cognition and neuropathology and biochemistry of the brain. Both wild type and transgenic mice treated with R-alpha lipoic acid displayed significant reductions in markers of oxidative modifications. On the other hand, R-alpha lipoic acid had little effect on Y-maze performance throughout the study and did not decrease end-point amyloid-β load. These results suggest that, despite the clear role of oxidative stress in mediating amyloid pathology and cognitive decline in ageing and AβPP-transgenic mice, long-term antioxidant therapy, at levels within tolerable nutritional guidelines and which reduce oxidative modifications, have limited benefit.

Original languageEnglish (US)
Pages (from-to)156-164
Number of pages9
JournalFree Radical Research
Volume43
Issue number2
DOIs
StatePublished - 2009
Externally publishedYes

Fingerprint

Thioctic Acid
Oxidative stress
Alzheimer Disease
Biochemistry
Oxidative Stress
Antioxidants
Pathology
Amyloid
Cognition
Transgenic Mice
Brain
Prion Diseases
Amyloid beta-Protein Precursor
Prions
Nutrition
Parkinson Disease
Animals
Therapeutics
Animal Models
Aging of materials

Keywords

  • Alzheimer's disease
  • Amyloid-β
  • Antioxidant
  • R-alpha lipoic acid
  • Transgenic mice

ASJC Scopus subject areas

  • Biochemistry

Cite this

Siedlak, S. L., Casadesus, G., Webber, K. M., Pappolla, M., Atwood, C. S., Smith, M. A., & Perry, G. (2009). Chronic antioxidant therapy reduces oxidative stress in a mouse model of Alzheimer's disease. Free Radical Research, 43(2), 156-164. https://doi.org/10.1080/10715760802644694

Chronic antioxidant therapy reduces oxidative stress in a mouse model of Alzheimer's disease. / Siedlak, Sandra L.; Casadesus, Gemma; Webber, Kate M.; Pappolla, Miguel; Atwood, Craig S.; Smith, Mark A.; Perry, George.

In: Free Radical Research, Vol. 43, No. 2, 2009, p. 156-164.

Research output: Contribution to journalArticle

Siedlak, SL, Casadesus, G, Webber, KM, Pappolla, M, Atwood, CS, Smith, MA & Perry, G 2009, 'Chronic antioxidant therapy reduces oxidative stress in a mouse model of Alzheimer's disease', Free Radical Research, vol. 43, no. 2, pp. 156-164. https://doi.org/10.1080/10715760802644694
Siedlak, Sandra L. ; Casadesus, Gemma ; Webber, Kate M. ; Pappolla, Miguel ; Atwood, Craig S. ; Smith, Mark A. ; Perry, George. / Chronic antioxidant therapy reduces oxidative stress in a mouse model of Alzheimer's disease. In: Free Radical Research. 2009 ; Vol. 43, No. 2. pp. 156-164.
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