What is Alzheimer’s disease (AD)?

Alzheimer’s disease (AD) is a progressive neurological disorder that affects the brain, primarily causing problems with memory, thinking, and behavior. It is the most common cause of dementia.

In Alzheimer’s disease, abnormal protein deposits, such as beta-amyloid plaques and tau tangles, build up in the brain, disrupting communication between nerve cells and causing them to die. Over time, this leads to the shrinkage of brain tissue and the gradual decline of cognitive function.

The exact cause of Alzheimer’s disease is not fully understood, but it is believed to involve a combination of genetic, environmental, and lifestyle factors. Age is the most significant risk factor, with the likelihood of developing Alzheimer’s disease increasing as people get older. Other risk factors include family history, certain genetic mutations, cardiovascular disease, diabetes, and a history of head injuries.

What is the relationship between AD and oxidative stress?

Oxidative stress refers to an imbalance between the production of reactive oxygen species (ROS) and the body’s ability to neutralize them with antioxidants. In AD, oxidative stress plays a significant role in the pathophysiology of the disease and contributes to neuronal damage, neuroinflammation, and the progression of cognitive decline.

Several factors contribute to oxidative stress in Alzheimer’s disease:

  • Beta-Amyloid Accumulation: Beta-amyloid plaques, one of the hallmark pathological features of AD, can induce oxidative stress in the brain. Beta-amyloid aggregates can generate ROS and impair mitochondrial function, leading to oxidative damage to neurons.
  • Tau Protein Pathology: Abnormal phosphorylation and aggregation of tau protein, another characteristic feature of AD, can lead to oxidative stress and neuronal dysfunction. Tau pathology disrupts cellular processes and contributes to mitochondrial dysfunction, further exacerbating oxidative stress.
  • Mitochondrial Dysfunction: Mitochondria are the primary source of ROS production in cells. In AD, mitochondrial dysfunction occurs early in the disease process, leading to increased ROS production and oxidative damage to neurons.
  • Inflammation: Neuroinflammation is a prominent feature of AD and contributes to oxidative stress. Microglia, the immune cells of the brain, become activated in response to beta-amyloid deposition and release pro-inflammatory cytokines and ROS, exacerbating neuronal damage.
  • Metal Ion Dysregulation: Dysregulation of metal ions, such as iron and copper, in the brain can promote ROS production and oxidative stress. Metal ions can interact with beta-amyloid and tau proteins, leading to the generation of ROS and oxidative damage.

Overall, oxidative stress is closely intertwined with the pathological processes of Alzheimer’s disease and contributes to neurodegeneration, synaptic dysfunction, and cognitive impairment.