Reference measurement procedures for Alzheimer's disease cerebrospinal fluid biomarkers: definitions and approaches with focus on amyloid β42.
Cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) are increasingly used in clinical settings, research and drug trials. However, their broad-scale use on different technology platforms is hampered by the lack of standardization at the level of sample handling, determination of concentrations of analytes and the absence of well-defined performance criteria for in vitro diagnostic or companion diagnostic assays, which influences the apparent concentration of the analytes measured and the subsequent interpretation of the data. There is a need for harmonization of CSF AD biomarker assays that can reliably, across centers, quantitate CSF biomarkers with high analytical precision, selectivity and stability over long time periods. In this position paper, we discuss reference procedures for the measurement of CSF AD biomarkers, especially amyloid β42 and tau. We describe possible technical approaches, focusing on a selected reaction monitoring mass spectrometry assay as a candidate reference method for quantification of CSF amyloid β42.
Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden. niklas.mattsson@neuro.gu.se
Niklas
N
Mattsson
Ingrid
I
Zegers
Ulf
U
Andreasson
Maria
M
Bjerke
Marinus A
MA
Blankenstein
Robert
R
Bowser
Maria C
MC
Carrillo
Johan
J
Gobom
Theresa
T
Heath
Rand
R
Jenkins
Andreas
A
Jeromin
June
J
Kaplow
Daniel
D
Kidd
Omar F
OF
Laterza
Andrew
A
Lockhart
Michael P
MP
Lunn
Robert L
RL
Martone
Kevin
K
Mills
Josef
J
Pannee
Marianne
M
Ratcliffe
Leslie M
LM
Shaw
Adam J
AJ
Simon
Holly
H
Soares
Charlotte E
CE
Teunissen
Marcel M
MM
Verbeek
Robert M
RM
Umek
Hugo
H
Vanderstichele
Henrik
H
Zetterberg
Kaj
K
Blennow
Erik
E
Portelius
D000544:Alzheimer Disease / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid* / Q000592:standards; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002851:Chromatography, High Pressure Liquid / Q000592:standards; D004797:Enzyme-Linked Immunosorbent Assay / Q000592:standards; D006801:Humans; D010446:Peptide Fragments / Q000134:cerebrospinal fluid* / Q000592:standards; D012107:Research Design / Q000592:standards*; D053719:Tandem Mass Spectrometry / Q000592:standards; D016875:tau Proteins / Q000134:cerebrospinal fluid
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins