Alzheimer's disease approaches - Focusing on pathology, biomarkers and clinical trial candidates

Prog Neuropsychopharmacol Biol Psychiatry. 2024 Aug 30:134:111069. doi: 10.1016/j.pnpbp.2024.111069. Epub 2024 Jun 23.

Abstract

The strategy for the development of new drugs for Alzheimer's disease (AD) recognizes that an effective therapy requires early therapeutic intervention and a multifactorial approach that considers the individual initiators of AD development. Current knowledge of AD includes the understanding of pathophysiology, risk factors, biomarkers, and the evolving patterns of biomarker abnormalities. This knowledge is essential in identifying potential molecular targets for new drug development. This review summarizes promising AD drug candidates, many of which are currently in phase 2 or 3 clinical trials. New agents are classified according to the Common Alzheimer's Disease Research Ontology (CADRO). The main targets of new drugs for AD are processes related to amyloid beta and tau neurotoxicity, neurotransmission, inflammation, metabolism and bioenergetics, synaptic plasticity, and oxidative stress. These interventions are aimed at preventing disease onset and slowing or eliminating disease progression. The efficacy of pharmacotherapy may be enhanced by combining these drugs with other treatments, antioxidants, and dietary supplements. Ongoing research into AD pathophysiology, risk factors, biomarkers, and the dynamics of biomarker abnormalities may contribute to the understanding of AD and offer hope for effective therapeutic strategies in the near future.

Keywords: Alzheimer's disease; Amyloid beta; Clinical trial; Drug development; Tau protein, disease-modifying drugs.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease* / drug therapy
  • Alzheimer Disease* / metabolism
  • Animals
  • Biomarkers* / metabolism
  • Clinical Trials as Topic* / methods
  • Humans

Substances

  • Biomarkers