Perspective on future role of biological markers in clinical therapy trials of Alzheimer's disease: A long-range point of view beyond 2020

Harald Hampel, Simone Lista, Stefan J. Teipel, Francesco Garaci, Robert Nisticò, Kaj Blennow, Henrik Zetterberg, Lars Bertram, Charles Duyckaerts, Hovagim Bakardjian, Alexander Drzezga, Olivier Colliot, Stéphane Epelbaum, Karl Broich, Stéphane Lehéricy, Alexis Brice, Zaven S. Khachaturian, Paul S. Aisen, Bruno Dubois

Research output: Contribution to journalArticle

Abstract

Recent advances in understanding the molecular mechanisms underlying various paths toward the pathogenesis of Alzheimer's disease (AD) has begun to provide new insight for interventions to modify disease progression. The evolving knowledge gained from multidisciplinary basic research has begun to identify new concepts for treatments and distinct classes of therapeutic targets; as well as putative disease-modifying compounds that are now being tested in clinical trials. There is a mounting consensus that such disease modifying compounds and/or interventions are more likely to be effectively administered as early as possible in the cascade of pathogenic processes preceding and underlying the clinical expression of AD. The budding sentiment is that "treatments" need to be applied before various molecular mechanisms converge into an irreversible pathway leading to morphological, metabolic and functional alterations that characterize the pathophysiology of AD. In light of this, biological indicators of pathophysiological mechanisms are desired to chart and detect AD throughout the asymptomatic early molecular stages into the prodromal and early dementia phase. A major conceptual development in the clinical AD research field was the recent proposal of new diagnostic criteria, which specifically incorporate the use of biomarkers as defining criteria for preclinical stages of AD. This paradigm shift in AD definition, conceptualization, operationalization, detection and diagnosis represents novel fundamental opportunities for the modification of interventional trial designs. This perspective summarizes not only present knowledge regarding biological markers but also unresolved questions on the status of surrogate indicators for detection of the disease in asymptomatic people and diagnosis of AD.

Original languageEnglish
Pages (from-to)426-449
Number of pages24
JournalBiochemical Pharmacology
Volume88
Issue number4
DOIs
Publication statusPublished - Apr 15 2014

Keywords

  • Alzheimer's disease
  • Clinical trials
  • CSF/blood biomarkers
  • PET imaging markers
  • Structural/functional MRI markers

ASJC Scopus subject areas

  • Pharmacology
  • Biochemistry

Fingerprint Dive into the research topics of 'Perspective on future role of biological markers in clinical therapy trials of Alzheimer's disease: A long-range point of view beyond 2020'. Together they form a unique fingerprint.

  • Cite this

    Hampel, H., Lista, S., Teipel, S. J., Garaci, F., Nisticò, R., Blennow, K., Zetterberg, H., Bertram, L., Duyckaerts, C., Bakardjian, H., Drzezga, A., Colliot, O., Epelbaum, S., Broich, K., Lehéricy, S., Brice, A., Khachaturian, Z. S., Aisen, P. S., & Dubois, B. (2014). Perspective on future role of biological markers in clinical therapy trials of Alzheimer's disease: A long-range point of view beyond 2020. Biochemical Pharmacology, 88(4), 426-449. https://doi.org/10.1016/j.bcp.2013.11.009