Biomarkers for Alzheimer's disease therapeutic trials

Harald Hampel, Gordon Wilcock, Sandrine Andrieu, Paul Aisen, Kaj Blennow, K. Broich, Maria Carrillo, Nick C. Fox, Giovanni B. Frisoni, Maria Isaac, Simon Lovestone, Agneta Nordberg, David Prvulovic, Christina Sampaio, Philip Scheltens, Michael Weiner, Bengt Winblad, Nicola Coley, Bruno Vellas

Research output: Contribution to journalArticlepeer-review

Abstract

The development of disease-modifying treatments for Alzheimer's disease requires innovative trials with large numbers of subjects and long observation periods. The use of blood, cerebrospinal fluid or neuroimaging biomarkers is critical for the demonstration of disease-modifying therapy effects on the brain. Suitable biomarkers are those which reflect the progression of AD related molecular mechanisms and neuropathology, including amyloidogenic processing and aggregation, hyperphosphorylation, accumulation of tau and neurofibrillary tangles, progressive functional, metabolic and structural decline, leading to neurodegeneration, loss of brain tissue and cognitive symptoms. Biomarkers should be used throughout clinical trial phases I-III of AD drug development. They can be used to enhance inclusion and exclusion criteria, or as baseline predictors to increase the statistical power of trials. Validated and qualified biomarkers may be used as outcome measures to detect treatment effects in pivotal clinical trials. Finally, biomarkers can be used to identify adverse effects. Questions regarding which biomarkers should be used in clinical trials, and how, are currently far from resolved. The Oxford Task Force continues and expands the work of our previous international expert task forces on disease-modifying trials and on endpoints for Alzheimer's disease clinical trials. The aim of this initiative was to bring together a selected number of key international opinion leaders and experts from academia, regulatory agencies and industry to condense the current knowledge and state of the art regarding the best use of biological markers in Alzheimer's disease therapy trials and to propose practical recommendations for the planning of future AD trials.

Original languageEnglish
Pages (from-to)579-593
Number of pages15
JournalProgress in Neurobiology
Volume95
Issue number4
DOIs
Publication statusPublished - Dec 2011

Keywords

  • Alzheimer's disease
  • Biomarkers
  • Early diagnosis
  • Neuroimaging

ASJC Scopus subject areas

  • Neuroscience(all)

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