Recent Advances in Alzheimer's Drug Discovery Research
Pp. 26-98 (73)
Sathyanarayanan V. Puthanveettil
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.
Alzheimer’s Disease, Drug Development, Pharmacotherapeutic
Targets, Transgenic Models.