Monitoring the amyloid beta-peptide in vivo--caveat emptor.
As a wave of 'disease modifying' (DM) therapies for Alzheimer's disease (AD) progresses towards the later stages of clinical development, an evaluation of our ability to measure relevant pharmacodynamic effects of such therapies is warranted. Reducing accumulation of amyloid beta (Abeta)-peptide in the brain parenchyma is the primary objective of most current DM approaches. Although a number of methods are available to measure Abeta in blood, cerebrospinal fluid (CSF) and the cerebrum, putative DM-induced changes in the levels of the peptides may not be fully captured, and the reasons for any such changes are not fully understood. Additional candidate biofluid (tau and isoprostanes) and imaging (MRI, FDG-PET) measures may provide alternative supporting evidence of drug activity and subsequent clinical efficacy in patient populations.
Thompson
Paul W
PW
GlaxoSmithKline, R&D China, UK Hub, Cambridge, UK.
Lockhart
Andrew
A
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D002986:Clinical Trials as Topic; D006801:Humans; D028421:Isoprostanes / Q000032:analysis / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods; D049268:Positron-Emission Tomography / Q000379:methods; D016875:tau Proteins / Q000032:analysis / Q000378:metabolism
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D028421:Isoprostanes; D016875:tau Proteins