Accelerating Alzheimer’s Disease Research by Pharmacologic, Genetic, and Computational Based Animal Models

Alzheimer’s disease (AD) is a type of dementia characterized pathologically by inappropriate neuronal loss in the specific brain regions, mainly in the hippocampus and cerebral cortex, where an accumulation of insoluble plaques of amyloid-beta (Aβ) and tau tangles formation occurs, resulting in progressive memory loss, impaired thinking, deterioration and changes in personality and mood. Alzheimer’s disease now possesses a significant health burden and is considered the main source of inability among aged individuals. Recently, Alzheimer's Disease International (ADI) evaluations of 2019 featured that there would be more than 50 million individuals living with dementia around the world, a figure set to increment to 152 million by 2050. Somebody creates dementia-like clockwork, and the current year expense of dementia is assessed at US $1trillion, a figure set to twofold by 2030. AD is the leading cause of dementia and accounts for 60-80% of cases. In spite of the fact that Aβ conglomeration and neurofibrillary tangles (NFTs) development are notable major causative components engaged with AD pathogenesis, the researchers failed to cure or prevent progression of disease effectively by focusing on these pathogenic variables. Thus, tackling AD is a complex job, as we have erudite lately by continuous phase III clinical trial programs failures. Due to the lack of a clear etiology and increased morbidity associated with Alzheimer's disease, there is an immediate need to investigate the underlying causes of the disease and design and develop novel therapeutic agents to slow or reverse disease progression. Animal models mimicking different types of ADlike pathological conditions, which is an essential component in discovering potential therapeutic targets and studying mechanism of action behind that therapeutic agent, as we know, are primary tools in the field of biomedical research including AD. This chapter discusses emerging pathophysiological mechanisms and drug targets, as well as a summary of in-vivo/ex-vivo, in-vitro, QSAR, and in-silico models commonly used in Alzheimer's disease research. Moreover, we will also describe how to select suitable and valid models and the specifications and relevance of a couple of behavioral assessment methods.

Keywords: Alzheimer’s disease, Behavioral animal models, In-silico models, Therapeutic strategies, Transgenic animal models.