Effect of Patient-Specific Preanalytic Variables on CSF Aβ1-42 Concentrations Measured on an Automated Chemiluminescent Platform.


Journal

The journal of applied laboratory medicine
ISSN: 2576-9456
Titre abrégé: J Appl Lab Med
Pays: England
ID NLM: 101693884

Informations de publication

Date de publication:
01 03 2021
Historique:
received: 26 03 2020
accepted: 28 07 2020
pubmed: 30 11 2020
medline: 16 10 2021
entrez: 29 11 2020
Statut: ppublish

Résumé

Cerebrospinal fluid (CSF) biomarkers are increasingly used to confirm the accuracy of a clinical diagnosis of mild cognitive impairment or dementia due to Alzheimer disease (AD). Recent evidence suggests that fully automated assays reduce the impact of some preanalytical factors on the variability of these measures. This study evaluated the effect of several preanalytical variables common in clinical settings on the variability of CSF β-amyloid 1-42 (Aβ1-42) concentrations. Aβ1-42 concentrations were measured using the LUMIPULSE G1200 from both freshly collected and frozen CSF samples. Preanalytic variables examined were: (1) patient fasting prior to CSF collection, (2) blood contamination of specimens, and (3) aliquoting specimens sequentially over the course of collection (i.e., CSF gradients). Patient fasting did not significantly affect CSF Aβ1-42 levels. While assessing gradient effects, Aβ1-42 concentrations remained stable within the first 5 1-mL aliquots. However, there is evidence of a gradient effect toward higher concentrations over successive aliquots. Aβ1-42 levels were stable when fresh CSF samples were spiked with up to 2.5% of blood. However, in frozen CSF samples, even 0.25% blood contamination significantly decreased Aβ1-42 concentrations. The preanalytical variables examined here do not have significant effects on Aβ1-42 concentrations if fresh samples are processed within 2 h. However, a gradient effect can be observed on Aβ1-42 concentrations after the first 5 mL of collection and blood contamination has a significant impact on Aβ1-42 concentrations once specimens have been frozen.

Sections du résumé

BACKGROUND
Cerebrospinal fluid (CSF) biomarkers are increasingly used to confirm the accuracy of a clinical diagnosis of mild cognitive impairment or dementia due to Alzheimer disease (AD). Recent evidence suggests that fully automated assays reduce the impact of some preanalytical factors on the variability of these measures. This study evaluated the effect of several preanalytical variables common in clinical settings on the variability of CSF β-amyloid 1-42 (Aβ1-42) concentrations.
METHODS
Aβ1-42 concentrations were measured using the LUMIPULSE G1200 from both freshly collected and frozen CSF samples. Preanalytic variables examined were: (1) patient fasting prior to CSF collection, (2) blood contamination of specimens, and (3) aliquoting specimens sequentially over the course of collection (i.e., CSF gradients).
RESULTS
Patient fasting did not significantly affect CSF Aβ1-42 levels. While assessing gradient effects, Aβ1-42 concentrations remained stable within the first 5 1-mL aliquots. However, there is evidence of a gradient effect toward higher concentrations over successive aliquots. Aβ1-42 levels were stable when fresh CSF samples were spiked with up to 2.5% of blood. However, in frozen CSF samples, even 0.25% blood contamination significantly decreased Aβ1-42 concentrations.
CONCLUSIONS
The preanalytical variables examined here do not have significant effects on Aβ1-42 concentrations if fresh samples are processed within 2 h. However, a gradient effect can be observed on Aβ1-42 concentrations after the first 5 mL of collection and blood contamination has a significant impact on Aβ1-42 concentrations once specimens have been frozen.

Identifiants

pubmed: 33249440
pii: 6010325
doi: 10.1093/jalm/jfaa145
pmc: PMC8482291
mid: NIHMS1737270
doi:

Substances chimiques

Amyloid beta-Peptides 0
Peptide Fragments 0
tau Proteins 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

397-408

Subventions

Organisme : NIA NIH HHS
ID : P30 AG066507
Pays : United States
Organisme : NIA NIH HHS
ID : U19 AG033655
Pays : United States

Informations de copyright

© American Association for Clinical Chemistry 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Références

Int J Alzheimers Dis. 2010 Jul 15;2010:
pubmed: 20798852
Alzheimers Dement. 2015 May;11(5):549-60
pubmed: 25282381
Lancet Neurol. 2007 Aug;6(8):734-46
pubmed: 17616482
Neurocrit Care. 2006;4(2):153-62
pubmed: 16627907
Front Aging Neurosci. 2018 Aug 22;10:253
pubmed: 30186152
Alzheimer Dis Assoc Disord. 2005 Oct-Dec;19(4):220-5
pubmed: 16327349
JAMA. 2009 Jul 22;302(4):385-93
pubmed: 19622817
Alzheimers Res Ther. 2019 Jul 19;11(1):63
pubmed: 31324260
Alzheimers Dement. 2018 Oct;14(10):1313-1333
pubmed: 29940161
Acad Emerg Med. 2003 Feb;10(2):151-4
pubmed: 12574013
Alzheimers Dement. 2011 May;7(3):263-9
pubmed: 21514250
J Alzheimers Dis. 2011;26(2):255-62
pubmed: 21606567
Alzheimers Dement. 2017 Aug;13(8):885-892
pubmed: 28222302
J Cereb Blood Flow Metab. 2016 May;36(5):899-902
pubmed: 26945018
Fluids Barriers CNS. 2016 Aug 31;13(1):15
pubmed: 27581842
JAMA Neurol. 2019 Jul 15;:
pubmed: 31305929
Proteomics. 2005 Jan;5(1):290-6
pubmed: 15672452
Lancet. 2006 Jul 29;368(9533):387-403
pubmed: 16876668
Alzheimers Dement. 2012 Jan;8(1):65-73
pubmed: 22047631
J Neurosci Methods. 2010 Aug 30;191(2):244-8
pubmed: 20599557
Neurosurgery. 2005 Sep;57(3 Suppl):S4-16; discussion ii-v
pubmed: 16160425
Expert Rev Neurother. 2014 Jun;14(6):621-30
pubmed: 24852227
BMC Geriatr. 2013 Dec 19;13:137
pubmed: 24354549
Clin Chem. 2015 May;61(5):734-43
pubmed: 25869575

Auteurs

Jacqueline A Darrow (JA)

Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD.

Amanda Calabro (A)

Fujirebio Diagnostics, Inc., Malvern, PA.

Sara Gannon (S)

Fujirebio Diagnostics, Inc., Malvern, PA.

Amanze Orusakwe (A)

Fujirebio Diagnostics, Inc., Malvern, PA.

Rianne Esquivel (R)

Fujirebio Diagnostics, Inc., Malvern, PA.

C J Traynham (CJ)

Fujirebio Diagnostics, Inc., Malvern, PA.

Aruna Rao (A)

Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD.

Seema Gulyani (S)

Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD.

Kristina Khingelova (K)

Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD.

Karen Bandeen-Roche (K)

Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.

Marilyn Albert (M)

Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD.

Abhay Moghekar (A)

Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD.

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