Next Generation Drugs in Alzheimer's Disease Treatment: From Benchtop to Bedside

Alzheimer’s disease (AD), the most common cause of dementia in the elderly, is a neurodegenerative disorder characterized by severe and progressive cognitive impairment, including impaired decision making and orientation, inability to perform activities of daily living, language impairment and psycho-behavioural disturbances.

Molecular studies based on interdisciplinary approaches, including biochemical investigations, immunohistochemistry, molecular and cell biology, genetic approaches and animal models, have revealed that AD is a multifactorial disease with many different etiopathogenic mechanisms. The two major AD hallmarks are extracellular amyloid beta (A) plaques and intracellular neurofibrillary tangles (NFTs), but additional pathogenic mechanisms have been described, including inflammation, oxidative damage, iron dysregulation, cholesterol metabolism and other amyloid-independent hypotheses.

There are still no effective treatments to prevent, stop or revert AD: the existing treatments only provide symptomatic relief, but poorly affect the progression of the disease.

Current approved therapy is based on the cholinesterase inhibitors and NMDA receptor antagonists. These treatments are symptomatic and drug discovery has been directed, in recent years, to develop “disease modifying drugs” able to counteract the progression of AD by modifying the evolution of disease. Recent advances on diagnostic criteria for the disease based on biological markers, even in a preclinical phase, can facilitate the identification of new effective therapies, impacting on drug development and monitoring disease progression during therapeutic trials.

The aim of this work is to provide an overview on the main therapeutic approaches, summarizing current treatments and new molecules still under clinical development and also discussing new perspectives on therapeutic intervention.

Keywords: Alzheimer’s Disease (AD), neurodegeneration, AD treatment, AD prevention, clinical trials.