Alzheimer's Disease: Novel Targets and Investigational Drugs for Disease Modification

Novel agents addressing non-amyloid, non-tau targets in Alzheimer's Disease (AD) comprise 70% of the AD drug development pipeline of agents currently in clinical trials. Most of the target processes identified in the Common Alzheimer's Disease Research Ontology (CADRO) are represented by novel agents in trials. Inflammation and synaptic plasticity/neuroprotection are the CADRO categories with the largest number of novel candidate therapies. Within these categories, there are few overlapping targets among the test agents. Additional categories being evaluated include apolipoprotein E epsilon 4 (APOE4) effects, lipids and lipoprotein receptors, neurogenesis, oxidative stress, bioenergetics and metabolism, vascular factors, cell death, growth factors and hormones, circadian rhythm, and epigenetic regulators. We highlight current drugs being tested within these categories and their mechanisms. Trials will be informative regarding which targets can be modulated to produce a slowing of clinical decline. Possible therapeutic combinations of agents may be suggested by trial outcomes. Biomarkers are evolving in concert with new targets and novel agents, and biomarker outcomes offer a means of supporting disease modification by the putative treatment. Identification of novel targets and development of corresponding therapeutics offer an important means of advancing new treatments for AD.

Automated summary

Novel agents targeting non-amyloid, non-tau proteins in Alzheimer's Disease (AD) account for 70% of the drugs currently in clinical trials. Inflammation and synaptic plasticity/neuroprotection are the most common categories for novel therapies in AD research. Multiple categories, including APOE4 effects, lipids and lipoprotein receptors, neurogenesis, and oxidative stress, are being evaluated. Biomarkers are evolving in parallel with new targets and novel agents, providing a means of supporting disease modification. The identification and development of novel targets offer an important opportunity for advancing new AD treatments.