Importance of cerebrospinal fluid storage conditions for the Alzheimer's disease diagnostics on an automated platform.
Author(s): Ferrer R, Zhu N, Arranz J, Porcel I, El Bounasri S, Sánchez O, Torres S, Julve J, Lleó A, Blanco-Vaca F, Alcolea D, Tondo M
Publication: Clin Chem Lab Med, 2022, Vol. 60, Page 1058-1063
PubMed ID: 35405043 PubMed Review Paper? No
Purpose of Paper
This paper compared levels of amyloid beta protein fragment 1-42 (Aβ1-42), amyloid beta protein fragment 1-40 (Aβ1-40), phospho Tau (p-Tau), and total Tau (t-Tau) as well as the ratio of Aβ1-42 to Aβ1-40 between cerebrospinal fluid (CSF) specimens collected from patients with Alzheimer’s disease that were stored for 1-2, 8-9, and 15-16 days at 4°C; for 15–16 days at -20 °C; and for 2 days at room temperature followed by 13-14 days at −80 °C with CSF stored for 15-16 days at −80°C (reference).
Conclusion of Paper
Levels of Aβ1-42 and Aβ1-40 as well as the ratio of Aβ1-42 to Aβ1-40 were significantly lower after storage of CSF at 4°C compared to CSF stored at -80°C for 15–16 days (reference) but were not significantly affected by storage at -20°C for 15–16 days or 2 days at room temperature followed by 13-14 days at −80 °C. The authors calculated a correction factor for the ratio of Aβ1-42 to Aβ1-40 in CSF stored at 4°C and found that when applied it increased the Kappa index value for specimens stored for 1-2 days at 4°C (relative to CSF specimens stored at −80°C for 15–16 days), but did not change the Kappa index value for specimens stored for 8-9 days or 15-16 days at 4°C. There was no difference in p-Tau or t-Tau levels between specimens stored at 4°C or -20°C and those stored at -80°C.
Studies
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Study Purpose
This study compared levels of Aβ1-42, Aβ1-40, p-Tau, and t-Tau as well as the ratio of Aβ1-42 to Aβ1-40 between CSF stored for 1-2, 8-9, and 15-16 days at 4°C, for 15–16 days at −20 °C, and for 2 days at room temperature followed by 13-14 days at −80 °C with those in CSF stored for 15-16 at -80°C. Cerebrospinal fluid was collected via lumbar puncture from 11 patients (6 females and 5 males) with Alzheimer’s disease into polypropylene tubes. Blood was centrifuged at 2,000 g for 10 min at 4°C and aliquoted. Aliquots were stored for 15–16 days at -80°C (reference); for 1-2, 8-9, and 15-16 days at 4°C; for 15-16 days at −20 °C; and for 2 days at room temperature followed by 13-14 days at −80 °C. After storage, specimens were allowed to reach room temperature and levels of Aβ1-42, Aβ1-40, p-Tau, and t-Tau were quantified using the LUMIPULSE G600II.
Summary of Findings:
Levels of Aβ1-42 and Aβ1-40 as well as the ratio of Aβ1-42 to Aβ1-40 were significantly lower when CSF was stored at 4°C than CSF stored at −80°C for 15–16 days, but were not significantly affected by storage at -20°C for 15-16 days or 2 days at room temperature followed by 13-14 days at -80 °C. Importantly, the significance of differences observed during storage at 4°C was dependent on storage duration. Significantly lower Aβ1-42 levels were found in CSF stored at 4°C for any tested duration than when CSF was stored at -80°C for 15-16 days (8% P<0.01 after 1-2 days; 16% P<0.001 after 8-9 days; and 14% P<0.0001 after 15-16 days). Aβ1-40 levels were 8% lower in CSF stored at 4°C for either 8-9 or 15-16 days than CSF stored at -80°C for 15–16 days (P<0.01, and P<0.001, respectively). The ratio of Aβ1-42 to Aβ1-40 was lower in specimens stored at 4°C for 1-2 days (7%, P<0.01), 8-9 days (8%, P<0.01), and 15-16 days (6%, P<0.01) than in specimens stored at -80°C for 15-16 days. The authors calculated a correction factor for the ratio of Aβ1-42 to Aβ1-40 in CSF stored at 4°C and found that when applied it increased the Kappa index value (from 0.814 to 1.0) for specimens stored for 1-2 days at 4°C (relative to the reference stored at −80°C for 15–16 days, but did not change the Kappa index value for specimens stored for 8-9 days or 15-16 days at 4°C (0.814, both). There was no difference in p-Tau or t-Tau levels between specimens stored at 4°C or -20°C and those stored at -80°C.
Biospecimens
Preservative Types
- None (Fresh)
- Frozen
Diagnoses:
- Alzheimer's Disease
Platform:
Analyte Technology Platform Protein Clinical chemistry/auto analyzer Peptide Clinical chemistry/auto analyzer Pre-analytical Factors:
Classification Pre-analytical Factor Value(s) Storage Storage temperature 4°C
-20°C
-80°C
Room-temperature and -80°C
Storage Storage duration 1-2 days
8-9 days
15-16 days