ArticleAlzheimer's research & therapy2019
Towards a unified protocol for handling of CSF before β-amyloid measurements.
Article in Alzheimer's research & therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Relationship Between Cerebrospinal Fluid Alzheimer's Disease Biomarker Values Measured via Lumipulse Assays and Conventional ELISA: Single-Center Experience and Systematic Review.Journal of Alzheimer's disease : JAD · 2024Pooled it
- Pre-analytical guidelines for blood and CSF Biomarkers 2025: Recommendations from the NACC ADRC Biofluid Biomarker Best Practices Workgroup.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Targeting amyloid-β in Alzheimer's disease: A critical analysis of clinical trials and their implications for drug development.Iranian journal of basic medical sciences · 2026Review
- Evaluation of preanalytical factors on quantification of amyloid-β (1-42), phosphorylated tau 181, and total tau in cerebrospinal fluid.Laboratory medicine · 2025Article
- Medial temporal lobe atrophy patterns in early-versus late-onset amnestic Alzheimer's disease.Alzheimer's research & therapy · 2024Article
- Medial temporal lobe atrophy patterns in early- versus late-onset amnestic Alzheimer's disease.bioRxiv : the preprint server for biology · 2024Article
- CSF Biomarkers in Longitudinal Alzheimer Disease Cohorts: Pre-Analytic Challenges.Clinical chemistry · 2024Article
- Where to Draw Cerebrospinal Fluid from an External Ventricular Drain? Comparison of Cerebrospinal Fluid Parameters between Two Different Collection Sites.Diagnostics (Basel, Switzerland) · 2023Article
- Age-related and amyloid-beta-independent tau deposition and its downstream effects.Brain : a journal of neurology · 2023Article
- Plasma biomarkers for Alzheimer's disease: a field-test in a memory clinic.Journal of neurology, neurosurgery, and psychiatry · 2023Article
- Concentration gradients of monoamines, their precursors and metabolites in serial lumbar cerebrospinal fluid of neurologically healthy patients determined with a novel LC-MS/MS technique.Fluids and barriers of the CNS · 2023Article
- Outcome Measures for Disease-Modifying Trials in Parkinson's Disease: Consensus Paper by the EJS ACT-PD Multi-Arm Multi-Stage Trial Initiative.Journal of Parkinson's disease · 2023Article
- CSF Alzheimer Disease Biomarkers: Time-Varying Relationships With MCI Symptom Onset and Associations With Age, Sex, andNeurology · 2022Article
- Characterization of pre-analytical sample handling effects on a panel of Alzheimer's disease-related blood-based biomarkers: Results from the Standardization of Alzheimer's Blood Biomarkers (SABB) working group.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2022Article
- Nucleic acid liquid biopsies in Alzheimer's disease: current state, challenges, and opportunities.Heliyon · 2022Review
- Exploring discordant low amyloid beta and high neocortical tau positron emission tomography cases.Alzheimer's & dementia (Amsterdam, Netherlands) · 2022Article
- BACE1: A Key Regulator in Alzheimer's Disease Progression and Current Development of its Inhibitors.Current neuropharmacology · 2022Review
- State-of-the-art of lumbar puncture and its place in the journey of patients with Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2022Review
- Knowledge gaps in Alzheimer's disease immune biomarker research.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2021Review
- Developing the ATX(N) classification for use across the Alzheimer disease continuum.Nature reviews. Neurology · 2021Review
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundWidespread implementation of Alzheimer's disease biomarkers in routine clinical practice requires the establishment of standard operating procedures for pre-analytical handling of cerebrospinal fluid (CSF).
methodsHere, CSF collection and storage protocols were optimized for measurements of β-amyloid (Aβ). We investigated the effects of (1) storage temperature, (2) storage time, (3) centrifugation, (4) sample mixing, (5) blood contamination, and (6) collection gradient on CSF levels of Aβ. For each study participant, we used fresh CSF directly collected into a protein low binding (LoB) tube that was analyzed within hours after lumbar puncture (LP) as standard of truth. Aβ42 and Aβ40 were measured in de-identified CSF samples using EUROIMMUN and Mesoscale discovery assays.
resultsCSF Aβ42 and Aβ40 were stable for at least 72 h at room temperature (RT), 1 week at 4 °C, and 2 weeks at - 20 °C and - 80 °C. Centrifugation of non-blood-contaminated CSF or mixing of samples before the analysis did not affect Aβ levels. Addition of 0.1-10% blood to CSF that was stored at RT without centrifugation led to a dose- and time-dependent decrease in Aβ42 and Aβ40, while Aβ42/Aβ40 did not change. The effects of blood contamination were mitigated by centrifugation and/or storage at 4 °C or - 20 °C. Aβ levels did not differ between the first to fourth 5-ml portions of CSF.
conclusionsCSF can be stored for up to 72 h at RT, 1 week at 4 °C, or at least 2 weeks at either - 20 °C or - 80 °C before Aβ measurements. Centrifugation of fresh non-blood-contaminated CSF after LP, or mixing before analysis, is not required. In case of visible blood contamination, centrifugation and storage at 4 °C or - 20 °C is recommended. After discarding the first 2 ml, any portion of up to 20 ml of CSF is suitable for Aβ analysis. These findings will be important for the development of a clinical routine protocol for pre-analytical handling of CSF.
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