Trial reportAlzheimer's research & therapy2015
An integrated multi-study analysis of intra-subject variability in cerebrospinal fluid amyloid-β concentrations collected by lumbar puncture and indwelling lumbar catheter.
Trial report in Alzheimer's research & therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 32 citations in OpenAlex.
- Sleep Deprivation Affects Tau Phosphorylation in Human Cerebrospinal Fluid.Annals of neurology · 2020Trial
- Increased Cerebrospinal Fluid Amyloid-β During Sleep Deprivation in Healthy Middle-Aged Adults Is Not Due to Stress or Circadian Disruption.Journal of Alzheimer's disease : JAD · 2020Trial
- Overnight Dynamics of Ventricular Cerebrospinal Fluid Amyloid-Beta, Lactate and Hypocretin in Patients With Hydrocephalus: A Pilot Study.Journal of sleep research · 2026Observational
- Mass Spectrometry-Based Quantification of Orexin Species in Human Cerebrospinal Fluid Reveals Differential Dynamics Associated with Sleep.medRxiv : the preprint server for health sciences · 2025Article
- The circadian clock regulates scavenging of fluid-borne substrates by brain border-associated macrophages.bioRxiv : the preprint server for biology · 2025Article
- Effects of time of the day at sampling on CSF and plasma levels of Alzheimer' disease biomarkers.Alzheimer's research & therapy · 2024Article
- Dysregulated clock gene expression and abnormal diurnal regulation of hippocampal inhibitory transmission and spatial memory in amyloid precursor protein transgenic mice.Neurobiology of disease · 2021Article
- Sleep and its regulation: An emerging pathogenic and treatment frontier in Alzheimer's disease.Progress in neurobiology · 2021Review
- Diurnal Patterns for Cortisol, Cortisone and Agouti-Related Protein in Human Cerebrospinal Fluid and Blood.The Journal of clinical endocrinology and metabolism · 2020Article
- The effect of lumbar puncture on the neurodegeneration biomarker neurofilament light in macaque monkeys.Alzheimer's & dementia (Amsterdam, Netherlands) · 2020Article
- Reduced non-rapid eye movement sleep is associated with tau pathology in early Alzheimer's disease.Science translational medicine · 2019Observational
- Amyloid β peptides are differentially vulnerable to preanalytical surface exposure, an effect incompletely mitigated by the use of ratios.Alzheimer's & dementia (Amsterdam, Netherlands) · 2018Article
- Effect of sleep on overnight cerebrospinal fluid amyloid β kinetics.Annals of neurology · 2018Article
- Pharmacological and Toxicological Properties of the Potent OralThe Journal of pharmacology and experimental therapeutics · 2017Article
- Diurnal oscillation of CSF Aβ and other AD biomarkers.Molecular neurodegeneration · 2017Article
- Associations Between β-Amyloid Kinetics and the β-Amyloid Diurnal Pattern in the Central Nervous System.JAMA neurology · 2017Article
- Diurnal Variation of Melatonin Concentration in the Cerebrospinal Fluid of Unanesthetized Microminipig.In vivo (Athens, Greece)Article
- Sez6 levels are elevated in cerebrospinal fluid of patients with inflammatory pain-associated conditions.Pain reportsArticle
Corrections and comments
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Authors and funding
23 authors at 14 institutions in 3 countries.
Funding
Abstract
introductionAmyloid-β (Aβ) has been investigated as a diagnostic biomarker and therapeutic drug target. Recent studies found that cerebrospinal fluid (CSF) Aβ fluctuates over time, including as a diurnal pattern, and increases in absolute concentration with serial collection. It is currently unknown what effect differences in CSF collection methodology have on Aβ variability. In this study, we sought to determine the effect of different collection methodologies on the stability of CSF Aβ concentrations over time.
methodsGrouped analysis of CSF Aβ levels from multiple industry and academic groups collected by either lumbar puncture (n=83) or indwelling lumbar catheter (n=178). Participants were either placebo or untreated subjects from clinical drug trials or observational studies. Participants had CSF collected by lumbar puncture or lumbar catheter for quantitation of Aβ concentration by enzyme linked immunosorbent assay. Data from all sponsors was converted to percent of the mean for Aβ40 and Aβ42 for comparison. Repeated measures analysis of variance was performed to assess for factors affecting the linear rise of Aβ concentrations over time.
resultsAnalysis of studies collecting CSF via lumbar catheter revealed tremendous inter-subject variability of Aβ40 and Aβ42 as well as an Aβ diurnal pattern in all of the sponsors' studies. In contrast, Aβ concentrations from CSF samples collected at two time points by lumbar puncture showed no significant differences. Repeated measures analysis of variance found that only time and draw frequency were significantly associated with the slope of linear rise in Aβ40 and Aβ42 concentrations during the first 6 hours of collection.
conclusionsBased on our findings, we recommend minimizing the frequency of CSF draws in studies measuring Aβ levels and keeping the frequency standardized between experimental groups. The Aβ diurnal pattern was noted in all sponsors' studies and was not an artifact of study design. Averaging Aβ concentrations at each time point is recommended to minimize the effect of individual variability. Indwelling lumbar catheters are an invaluable research tool for following changes in CSF Aβ over 24-48 hours, but factors affecting Aβ concentration such as linear rise and diurnal variation need to be accounted for in planning study designs.
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