Inter-laboratory variation in cerebrospinal fluid biomarkers for Alzheimer's disease: united we stand, divided we fall.
Abstract Several drug candidates for Alzheimer's disease are being evaluated in clinical trials, with the goal of finding a drug with disease-modifying effects. When such a drug finally reaches the market, there will be a demand for accurate diagnostic tools useful for early detection of disease and for monitoring biochemical effects. The core cerebrospinal fluid (CSF) biomarkers amyloid peptides (Abeta42), total-tau and phospo-tau are promising in this respect. However, inter-center variation (caused by pre-analytical, analytical and post-analytical factors), and inter-laboratory variation (caused by analytical factors), particularly for CSF Abeta42, lowers their utility in multicenter studies. Here, we discuss the causes of these variations, and present a global quality control program to overcome them.
Mattsson
Niklas
N
Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy, University of Gothenburg, Institute of Neuroscience and Physiology, Göteborg and Mölndal, Sweden. niklas.mattsson@neuro.gu.se
Blennow
Kaj
K
Zetterberg
Henrik
H
D000544:Alzheimer Disease / Q000175:diagnosis*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D019411:Clinical Laboratory Techniques / Q000592:standards; D007755:Laboratories, Hospital; D015588:Observer Variation; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D011786:Quality Control; D012016:Reference Values; D016875:tau Proteins / Q000134:cerebrospinal fluid
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins