What is the role of oxidative stress in the pathophysiology of Alzheimer disease (AD) in Down syndrome (DS)?

Updated: Nov 13, 2019
  • Author: Norberto Alvarez, MD; Chief Editor: Jasvinder Chawla, MD, MBA  more...
  • Print
Answer

Answer

The accumulation of ROSs, a result of mitochondrial dysfunction that occurs in persons with DS, leads to abnormal lipid peroxidation metabolism that could lead to structural damage to membranes and the generation to more toxic products. ROS-related activity also leads to DNA damage.

All these findings lead to the concept that oxidative stress, defined as the lack of balance between the production and the removal of ROSs, might play an important role in the development of AD in persons with DS; however, oxidative stress alone does not explain the whole process. [27]

The corollary of this theory was the use of antioxidants as a therapeutic tool in the treatment and prevention of AD and of AD in DS. However, this therapy proved to be ineffective. [44]

An alternative hypothesis for the amyloid cascade suggests that increased oxidative stress, secondary to pathogenic factors, increase Abeta, which behaves as a redox sensor. In this alternative hypothesis, Abeta acting as a redox sensor attenuates oxidative stress. If this proves to be true, then oxidative-induced Abeta might be a brain protector. [45]   


Did this answer your question?
Additional feedback? (Optional)
Thank you for your feedback!