Recent Advances in Alzheimer's Drug Discovery Research

Alzheimer’s disease (AD) is the most common cause of age-related dementia, a deleterious neurodegenerative disorder that impairs memory, where neuropathological changes develop gradually over years to affect cognitive functions. AD is one of the most important health-care problems with over 20 million people suffering worldwide and has become a critical issue to human health, especially in aging societies. Current treatments do not prevent, stop, or delay disease progression, despite the considerable advances in knowledge of the pathogenesis of AD and in medicinal chemistry over the past quarter of a century. The neuropathologic hallmarks of AD are extracellular senile plaques of aggregated β-amyloid and intracellular neurofibrillary tangles, mainly containing the hyperphosphorylated microtubuleassociated protein tau. Additional changes that may also occur in the brains of AD patients include age-related brain atrophy, synaptic pathology, and neuron loss, which contribute to cognitive impairment. So far, only four cholinesterase inhibitors and memantine have been marketed as the therapeutic strategies for Alzheimer’s disease. Despite advancements in prevention strategies, potential targets, effective biomarkers, clinical development methods, and the evaluation of potential treatments in clinical trials. This chapter summarizes our best understanding of the etiology, animal models currently under study, pharmacotherapeutic targets, and molecular pathways that curtail the progression of AD. This knowledge will help to strategize the development and clinical use of any new drugs for AD therapy in future.

Keywords: Alzheimer’s Disease, Drug Development, Pharmacotherapeutic Targets, Transgenic Models.