Pathways in the Drug Development for Alzheimer’s Disease (1906-2016): A Bibliometric Study

Investments in drug development for Alzheimer’s disease (AD) have not led to the availability of a treatment to cure or halt the progression of the disease. This study aimed to provide insights into the current lack of an effective therapy against AD by exploring the evolution of research paths in the scientific domains corresponding to fundamental, preclinical and clinical research from the identification of the disease in 1906 up to 2016. More specifically, the influence of the amyloid cascade hypothesis and use of animal models in the evolution of drug development for AD were explored. We used bibliometric analysis for the identification of research paths taken over time, including main path analysis, direct citation analysis and co-word analysis. The results show that the amyloid cascade hypothesis has played an important role in the evolution of research paths in the drug development process of AD. The preclinical domain and to a lesser extent the clinical domain, were found to be increasingly involved in the study of interventions modulating amyloid-beta related neurotoxicity over time in line with the fundamental domain predominantly focussing on amyloid-beta as the primary cause of AD. The results open up a discussion about lock-in, i.e. that decreasing options in the fundamental domain results in less room for manoeuvre in the preclinical and clinical domain.