Biomarkers for Alzheimer's disease therapeutic trials.
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.
Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Goethe-University, Frankfurt, Heinrich-Hoffmann-Str. 10, 60528 Frankfurt, Germany. harald.hampel@med.uni-frankfurt.de
Harald
H
Hampel
Gordon
G
Wilcock
Sandrine
S
Andrieu
Paul
P
Aisen
Kaj
K
Blennow
K
K
Broich
Maria
M
Carrillo
Nick C
NC
Fox
Giovanni B
GB
Frisoni
Maria
M
Isaac
Simon
S
Lovestone
Agneta
A
Nordberg
David
D
Prvulovic
Christina
C
Sampaio
Philip
P
Scheltens
Michael
M
Weiner
Bengt
B
Winblad
Nicola
N
Coley
Bruno
B
Vellas
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism*; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001931:Brain Mapping; D002986:Clinical Trials as Topic / Q000379:methods*; D006801:Humans; D011877:Radionuclide Imaging
D014150:Antipsychotic Agents; D015415:Biomarkers