Abstract
Background: Sample collection and preanalytical protocols may significantly impact the results of large-scale epidemiological studies incorporating blood-based biomarkers of neuropathology. Objective: To evaluate the stability and assay variability of several blood-based biomarkers of neuropathology for common preanalytical conditions. Methods: We collected serum and plasma samples from 41 participants and evaluated the effect of processing delay of up to 72 h when stored at 4°C, three freeze-thaw cycles, and a combination of 48-h processing delay when stored at 4°C and three freeze-thaw cycles on biomarker stability. Using the Simoa assay (Quanterix Inc.), we measured amyloid-β 40 (Aβ40), amyloid-β 42 (Aβ42), neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and phosphorylated tau 181 (p-tau-181). Results: We found that Aβ40 and Aβ42 levels significantly decreased after a 24-h processing delay in both plasma and serum samples, and a single freeze-thaw cycle (p < 0.0001). Nevertheless, serum Aβ42/40 ratio remained stable with a processing delay up to 48 h while plasma Aβ42/40 ratio showed only small but significant increase with a delay up to 72 h. Both plasma and serum GFAP and NfL levels were only modestly affected by processing delay and freeze-thaw cycles. Plasma p-tau-181 levels notably increased with a 24-, 48-, and 72-h processing delay, but remained stable in serum. Intra-individual variation over two weeks was minimal for all biomarkers and their levels were substantially lower in serum when compared with plasma. Conclusion: These results suggest that standardizing preanalytical variables will allow robust measurements of biomarkers of neuropathology in population studies.
Original language | English (US) |
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Pages (from-to) | 735-748 |
Number of pages | 14 |
Journal | Journal of Alzheimer's Disease |
Volume | 95 |
Issue number | 2 |
DOIs | |
State | Published - 2023 |
Bibliographical note
Publisher Copyright:© 2023 - IOS Press. All rights reserved.
Keywords
- Alzheimer's disease
- Simoa assay
- amyloid-β
- blood-based biomarkers
- pre-analytical variables
- stability
PubMed: MeSH publication types
- Journal Article
- Research Support, Non-U.S. Gov't