Impact of harmonization of collection tubes on Alzheimer's disease diagnosis.
Author(s): Lehmann S, Schraen S, Quadrio I, Paquet C, Bombois S, Delaby C, Dorey A, Dumurgier J, Hirtz C, Krolak-Salmon P, Laplanche JL, Moreaud O, Peoc'h K, Rouaud O, Sablonnière B, Thouvenot E, Touchon J, Vercruysse O, Hugon J, Gabelle A, Pasquier F, Perret-Liaudet A
Publication: Alzheimers Dement, 2014, Vol. 10, Page S390-S394.e2
PubMed ID: 24269268 PubMed Review Paper? No
Purpose of Paper
This paper investigated the effects of standardization of the collection tube type on the levels of β-amyloid 1–42 (Aβ42), total tau, and phosphorylated tau (p-tau) and on the Innotest Amyloid Tau Index (IATA) in cerebrospinal fluid (CSF) and the sensitivity of these markers for Alzheimer’s disease.
Conclusion of Paper
After the collection tube types were standardized to the Sarstedt tube, average values for Aβ42 and IATI were higher, levels of tau increased only slightly, and p-tau was unaffected. The optimal cut-off values for Aβ42 and the IATI were found to be significantly different before and after the switch in tube type. The sensitivity of the assay for detecting Alzheimer’s disease was dependent on use of the correct cut-off value.
Studies
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Study Purpose
This study investigated the effects of standardization of the collection tube type on the levels of Aβ42, total tau, and p-tau and on the IATA and the sensitivity of these markers for Alzheimer’s disease. CSF was collected, preferably in the morning, from 1149 patients at four different clinical and research centers within France, each of which used a different tube manufacturer (Greiner, Becton Dickinson, VWR, or CML), and from 817 patients after tube standardization in Sarstedt tubes (3 centers). Patients were classified as having Alzheimer’s disease (1113 patients by National Institute of Neurological and Communicative Disorders and Stroke criteria) or non-Alzheimer’s disease (863 patients including frontotemporal lobar degeneration, dementia, Parkinson’s disease, progressive supranuclear palsy, amyotrophic lateral sclerosis, normal pressure hydrocephalus, and psychiatric disorders). CSF was sent to the local laboratory within 4 h of collection, centrifuged for 10 min at 1000 x g at 4°C, and stored at -80°C in polypropylene tubes. Levels of Aβ42, total tau, and p-tau were measured simultaneously by ELISA using different batches of the kits over the years of the study.
Summary of Findings:
After the switch to Sarstedt tubes, average values increased for Aβ42 (1.56-1.72 fold) and the IATI (approximately 20%) but tau values only increased slightly (1.01-1.04 fold) and p-tau remained the same (0.94-1.00-fold). The area under the curves for Aβ42, total tau, and p-tau were comparable in specimens collected in the original four tube types and Sarstedt tubes. When cut-off values for each marker were chosen to maximize sensitivity and specificity using the highest Youden index, significantly different optimal cut-off values for Aβ42 and the IATI were found before and after the switch in tubes (P<0.01, both). Importantly, application of the original cut-off for Aβ42 resulted in sensitivity of 27-46% for specimens in Sarstedt tubes but this increased to 60-81% once the new cut-off was applied.
Biospecimens
Preservative Types
- Frozen
Diagnoses:
- Other diagnoses
- Alzheimer's Disease
Platform:
Analyte Technology Platform Protein ELISA Pre-analytical Factors:
Classification Pre-analytical Factor Value(s) Preaquisition Diagnosis/ patient condition Alzheimer’s Disease
Non-Alzheimer’s Disease
ELISA Specific Targeted peptide/protein Aβ42
total tau
p-tau
IATA
Biospecimen Acquisition Type of collection container/solution Greiner, Becton Dickinson, VWR or CML tube
Sarstedt tube