A novel Zebrafish model of Alzheimer's disease by Aluminium chloride; involving nitro-oxidative stress, neuroinflammation and cholinergic pathway

Alzheimer's disease (AD) is the most common form of dementia and is a progressive neurodegenerative disorder of the brain. Most AD experimental animal models are pharmacological or transgenic in origin. The existing pharmacological approaches for developing AD are poorly developed and most of them fail to replicate the complete characteristics of disease pathology. Developing a cost-effective and reliable experimental animal model will meet this research gap. Zebrafish (ZF) are progressively emerging as a powerful drug discovery disease model to evaluate central nervous system (CNS) disorders due to their homologous similarities to humans as well as cost-effectiveness. The present research is conceptualized to develop and evaluate a reliable ZF AD model using aluminum chloride (AlCl3). Chronic exposure of 0.04 mM of AlCl3 for 28 days increased the expression of amyloid-β, phosphorylated tau protein and senile plaque development in the ZF brain. The observed changes were associated with learning and memory impairment. Furthermore, decreased brain-derived neurotrophic factor (BDNF) level and elevated oxidative stress indices, pro-inflammatory cytokines levels and acetylcholine esterase (AChE) activity was observed upon exposure to AlCl3 in the ZF brain. Chronic exposure to 0.04 mM of AlCl3 would be a cost-effective ZF AD model for pharmacological screening and may also be used to unravel the molecular mechanism underlying the neuropathology of the disease.