The Role of Toll Like Receptor 4 in Pathogenesis of Alzheimer’s Disease Induced by Aluminium Chloride

Abstract

Amyloid plaques and neurofibrillary tangles are the neuropathological hallmarks of Alzheimer’s disease. β-amyloid peptides deposit as extracellular aggregate and form amyloid plaques that are thought to be toxic to the surrounding neurons. Accumulation of amyloid plaques is reported to be involved in synaptic dysfunction and cognitive impairment in Alzheimer’s disease. These deposits are associated with a robust microglial mediated inflammatory response. Toll like receptor 4 (TLR4) is important in the activation of innate immunity. The present study will focus on role of TLR4 in the pathogenesis of Alzheimer’s disease. In vivo model of Alzheimer’s disease was developed in Sprague Dawley rats by administering aluminium chloride (50 mg/kg) for 28 days by intra peritoneal route. After 28 days, memory test was done in all animals by morris water maze and then all animals were sacrificed and their brains were isolated for TLR4 gene expression using RT-PCR as well as quantification using ELISA kit. Results of the present study show that over expression of TLR4 in the brain of rats as well as loss of memory in rats treated with aluminium chloride. Thus upregulation of TLR4 plays an important role in the pathogenesis of aluminium chloride induced Alzheimer’s disease model. This study will be helpful in delaying the disease progression and provide promising therapeutic targets for treatment of Alzheimer’s disease.