Chronic oral exposure of aluminum chloride in rat modulates molecular and functional neurotoxic markers relevant to Alzheimer's disease

Toxicol Mech Methods. 2022 Oct;32(8):616-627. doi: 10.1080/15376516.2022.2058898. Epub 2022 Apr 7.


Aluminum is an environmentally abundant potential neurotoxic agent that may result in oxidative damage to a range of cellular biomarkers. The potential sources of aluminum accumulation in the body include drinking water, food, medicines, vaccines, and aluminum cookware utensils, etc. The accumulation of aluminum in the brain is reported to be associated with cholinergic dysfunction, oxidative stress and neuronal damage, which may ultimately cause Alzheimer's disease. Since chronic exposure to aluminum leads to its accumulation in the brain, so this study was done by a long-term (24 weeks) low dose (20 mg/kg) oral exposure of aluminum chloride in rats. In this chronic model, we have evaluated the major hallmarks of Alzheimer's disease including amyloid-beta (Aβ1-42) and phosphorylated-tau (p231-tau) protein in brain tissue. Furthermore, we evaluated the level of acetyl cholinesterase activity, inflammatory cytokines such as TNF-α, IL-6 and IL-1β, and oxidative stress biomarkers in the rat brain in this model. The neurobehavioral parameters were also assessed in animals by using spontaneous locomotor activity, passive avoidance, rotarod test and novel object recognition test to evaluate alteration in learning, memory and muscle co-ordination. We found that chronic oral exposure to aluminum chloride causes a significant increase in structural hallmarks such as Aβ1-42 and p231-tau levels along with pro-inflammatory cytokines (TNF-α and IL-6), oxidative stress, and a decrease in antioxidant markers such as GSH and catalase in the brain tissue. These biomarkers significantly affected neurobehavioral parameters in animals. This study provides a mechanistic understanding of chronic aluminum-induced neuronal toxicity in the brain with relevance to Alzheimer's disease.

Keywords: Aluminum chloride; Alzheimer’s disease; neuroinflammation; neurovegetative markers.

MeSH terms

  • Aluminum / toxicity
  • Aluminum Chloride / toxicity
  • Aluminum Compounds / toxicity
  • Alzheimer Disease* / chemically induced
  • Animals
  • Biomarkers / metabolism
  • Disease Models, Animal
  • Interleukin-6 / metabolism
  • Neurotoxicity Syndromes* / etiology
  • Oxidative Stress
  • Rats
  • Tumor Necrosis Factor-alpha / metabolism


  • Aluminum Compounds
  • Biomarkers
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Aluminum Chloride
  • Aluminum