Advances in Alzheimer's disease's pharmacological treatment

Abstract

Alzheimer's disease (AD) is the most common type of dementia in the elderly. Several hypotheses emerged from AD pathophysiological mechanisms. However, no neuronal protective or regenerative drug is available nowadays. Researchers still work in drug development and are finding new molecular targets to treat AD. Therefore, this study aimed to summarize main advances in AD pharmacological therapy. Clinical trials registered in the National Library of Medicine database were selected and analyzed accordingly to molecular targets, therapeutic effects, and safety profile. The most common outcome was the lack of efficacy. Only seven trials concluded that tested drugs were safe and induced any kind of therapeutic improvement. Three works showed therapeutic effects followed by toxicity. In addition to aducanumab recent FDA approval, antibodies against amyloid-β (Aβ) showed no noteworthy results. 5-HT6 antagonists, tau inhibitors and nicotinic agonists' data were discouraging. However, anti-Aβ vaccine, BACE inhibitor and anti-neuroinflammation drugs showed promising results.

Keywords: Alzheimer’s disease; drug development; molecular target; new drugs; pharmacological treatment.

FIGURE 1

Main potential targets for drug design in AD and relation of its pathways. (A) AD’s targets used to develop new drugs in clinical trials evaluated in this work. (B) All mechanisms related to AD pathogenesis and progression are connected and were explored in these clinical trials, such as Aβ and tau aggregation; BACE-1, γ-secretase, or glutaminyl cyclase activity; neuroinflammation; excitotoxicity; 5-HT7R or 5-HT6R hyperstimulation and cholinergic impairment.