Blood-based systems biology biomarkers for next-generation clinical trials in Alzheimer's disease

Harald Hampel, Andrea Vergallo, Mohammad Afshar, Leyla Akman-Anderson, Joaquín Arenas, Norbert Benda, Richard Batrla, Karl Broich, Filippo Caraci, A. Claudio Cuello, Enzo Emanuele, Marion Haberkamp, Steven J. Kiddle, Alejandro Lucía, Mark Mapstone, Steven R. Verdooner, Janet Woodcock, Simone Lista

Research output: Contribution to journalArticle


Alzheimer's disease (AD)-a complex disease showing multiple pathomechanistic alterations-is triggered by nonlinear dynamic interactions of genetic/epigenetic and environmental risk factors, which, ultimately, converge into a biologically heterogeneous disease. To tackle the burden of AD during early preclinical stages, accessible blood-based biomarkers are currently being developed. Specifically, next-generation clinical trials are expected to integrate positive and negative predictive blood-based biomarkers into study designs to evaluate, at the individual level, target druggability and potential drug resistance mechanisms. In this scenario, systems biology holds promise to accelerate validation and qualification for clinical trial contexts of use-including proof-of-mechanism, patient selection, assessment of treatment efficacy and safety rates, and prognostic evaluation. Albeit in their infancy, systems biology-based approaches are poised to identify relevant AD "signatures" through multifactorial and interindividual variability, allowing us to decipher disease pathophysiology and etiology. Hopefully, innovative biomarker-drug codevelopment strategies will be the road ahead towards effective disease-modifying drugs.

Original languageEnglish
Pages (from-to)177-191
Number of pages15
JournalDialogues in Clinical Neuroscience
Issue number2
Publication statusPublished - Jan 1 2019



  • Alzheimer’s disease
  • biomarker-drug codevelopment
  • blood-based biomarker
  • clinical trial
  • context of use
  • pathophysiology
  • precision medicine
  • predictive biomarker
  • systems biology

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Hampel, H., Vergallo, A., Afshar, M., Akman-Anderson, L., Arenas, J., Benda, N., Batrla, R., Broich, K., Caraci, F., Cuello, A. C., Emanuele, E., Haberkamp, M., Kiddle, S. J., Lucía, A., Mapstone, M., Verdooner, S. R., Woodcock, J., & Lista, S. (2019). Blood-based systems biology biomarkers for next-generation clinical trials in Alzheimer's disease
. Dialogues in Clinical Neuroscience, 21(2), 177-191.