Update on Alzheimer's Disease Therapeutics

Alzheimer’s disease (AD) is the leading cause of dementia worldwide. Clinically, it is characterized by progressive cognitive impairment and the emergence of neuropsychiatric disturbances. In recent years, many drug candidates aimed at disease modification have advanced into large, randomized controlled trials, but none have demonstrated efficacy in slowing down the relentless progression of AD. While the exact cause of AD is still being fervently investigated, the field is moving toward earlier identification and treatment of the disease, as it is believed this may be the main reason for so many clinical trial failures. There are currently four main mechanisms of action that are being actively developed in AD therapeutics: Drugs aimed at reducing Aβ production, notably secretase inhibitors; Drugs aimed at reducing Aβ plaque burden via inhibition of aggregatio or disruption of aggregates; Drugs aimed at promoting Aβ clearance via active or passive immunotherapy; and Drugs aimed at preventing tau protein phosphorylation. In this review, recent findings from clinical and preclinical studies in each of these categories will be discussed, as well as a category entitled ‘ other therapies,’ that includes treatments that do not fit under a single mechanism of action, but represent rational interventions for the underlying pathology of Alzheimer’s disease.