No correlation between time-linked plasma and CSF Aβ levels

Bastard, Nathalie Le; Aerts, Laetitia; Leurs, Judith; Blomme, Walter; Deyn, Peter Paul P De; Engelborghs, Sebastiaan

doi:10.1016/j.neuint.2009.08.006

Cited by 52 publications

(37 citation statements)

References 28 publications

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“…The present data, combined with the majority of the data from the literature, allows us to conclude that centrifugation (before or after freezing) does not affect CSF biomarker concentrations, probably not even when CSF is contaminated with blood. Although A␤ can also be found in plasma, originating from different pools such as platelets, muscle, and liver, its concentration is much lower than in CSF (23 ) and is therefore unlikely to significantly alter the concentrations measured in blood-contaminated CSF. Maximal differences of 9% and 7% for fractionated sampling and centrifugation, respectively, were smaller than the reported interassay CV for the assays used (10,17 ).…”

Section: Centrifugationmentioning

confidence: 98%

Importance and Impact of Preanalytical Variables on Alzheimer Disease Biomarker Concentrations in Cerebrospinal Fluid

2015

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BACKGROUND Analyses of cerebrospinal fluid (CSF) biomarkers (β-amyloid protein, total tau protein, and hyperphosphorylated tau protein) are part of the diagnostic criteria of Alzheimer disease. Different preanalytical sample procedures contribute to variability of CSF biomarker concentrations, hampering between-laboratory comparisons. The aim of this study was to explore the influence of fractionated sampling, centrifugation, freezing temperature, freezing delay, and freeze–thaw cycles on CSF biomarker analyses. METHODS We studied fractionated sampling in sequential aliquots of lumbar CSF. Centrifuged and noncentrifuged samples from the same fraction were compared. CSF samples were subjected to different protocols (liquid nitrogen, −80 °C, and −20 °C; 24 h at 2–8 °C; and 24 and 48 h at room temperature). To study the influence of freeze–thaw cycles, samples were thawed up to 4 times and refrozen at −80 °C. CSF was collected in polypropylene tubes. We measured CSF biomarker concentrations with commercially available single-analyte Innotest assays. RESULTS CSF biomarker concentrations from non–blood-contaminated samples are not influenced by centrifugation or fractionated sampling. Freezing temperature and delayed storage can affect biomarker concentrations; freezing of CSF samples at −80 °C as soon as possible after collection is recommended. Consecutive freezing and thawing of CSF samples up to 3 times had little effect. CONCLUSIONS Temperature of freezing, delay until freezing, and freeze–thaw cycles significantly influence CSF biomarker concentrations, stressing the need for standard operating procedures for preanalytical sample handling. The differences observed in this study are, however, relatively small, and the impact on the clinical value of these CSF biomarkers needs to be determined.

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Section: Centrifugationmentioning

confidence: 98%

Importance and Impact of Preanalytical Variables on Alzheimer Disease Biomarker Concentrations in Cerebrospinal Fluid

2015

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“…11 The authors emphasized the poor reliability that arose from using multiple, discrepant assays of plasma A␤. 11 The highly variable levels of plasma A␤42 and A␤40 in different studies, 13,[31][32][33][34] and the reported lack of significant associations between levels of A␤ in plasma and CSF, 14,35 may, in part, be explained by the variability and poor reliability of assays for plasma A␤ levels, i.e., there may indeed have been an association that was obscured by the excessive variability in the results from the plasma assay. In our study, we used a single assay with established low intraclass coefficients and high test-retest reliability, 7 thereby strengthening the reliability of the plasma A␤ findings.…”

Section: Statistical Analysesmentioning

confidence: 99%

Plasma Aβ and PET PiB binding are inversely related in mild cognitive impairment

Devanand

Schupf²,

Stern³

et al. 2011

Neurology

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Objective: To evaluate the relations between PET Pittsburgh compound B (PiB-PET) binding (amyloid imaging) and plasma A␤ in patients with mild cognitive impairment (MCI) and similarly aged controls. Methods:In 20 patients with MCI and 19 cognitively intact controls (case-control study), PiB binding potential (BP nd ) was assessed in 4 regions, and total brain excluding cerebellum, referenced to cerebellar binding. The mean of plasma A␤ levels measured in duplicate was analyzed.Results: Plasma A␤42/A␤40 ratio was decreased in MCI compared to controls (mean 0.15 SD 0.04 vs mean 0.19 SD 0.07, p ϭ 0.03) but A␤40 (p ϭ 0.3) and A␤42 (p ϭ 0.06) levels did not differ between the 2 groups. PiB BP nd was increased in MCI compared to controls in the cingulate (p ϭ 0.02), parietal (p ϭ 0.02), and total brain (p ϭ 0.03), but not in prefrontal cortex (p ϭ 0.08) or parahippocampal gyrus (p ϭ 0.07). Linear regression analyses adjusting for age, sex, and cognitive test scores showed that low A␤42/A␤40 ratio was associated with high cingulate, parietal, and total brain PiB binding (0.01Ͻ p Յ 0.05). These associations between PiB binding and the A␤42/A␤40 ratio were strongest in PiB-positive subjects and within the MCI group. Conclusions:

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“…Further, the fact that all the patients were taking psychotropic drugs during the ECT course may constitute a possible bias, although no influence of psychotropic medications on the plasma Aβ40/Aβ42 ratio was reported [39]. Moreover, the precise origin of plasma Aβ is not known and results regarding the relationship between peripheral blood and cerebrospinal fluid Aβ levels have been contradictory [57,58,59,60]. Therefore, a lack of data on cerebrospinal fluid may also be considered a limitation.…”

Section: Discussionmentioning

confidence: 99%

Plasma Amyloid-β Levels in Drug-Resistant Bipolar Depressed Patients Receiving Electroconvulsive Therapy

et al. 2013

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Aims: Alterations of plasma amyloid-β (Aβ) peptides have been related to a high risk for cognitive impairment and dementia. The present study aimed to measure plasma Aβ peptides (Aβ40, Aβ42) and the Aβ40/Aβ42 ratio in a sample of drug-resistant bipolar depressed patients, as well as to explore the possible correlation between biological parameters and clinical changes along an electroconvulsive therapy (ECT) course. Methods: Aβ40 and Aβ42 were measured by means of an ELISA assay in 25 drug-resistant bipolar depressed patients before (T0) and 1 week after (T1) the end of ECT. The patients were clinically evaluated by means of the Hamilton Rating Scale for Depression, 21-item (HRSD-21), the Mini-Mental State Examination, and the Clinical Global Impressions-Severity of Illness Scale. Results: Plasma Aβ levels and the Aβ40/Aβ42 ratio were similar at T0 and T1. The Aβ40/Aβ42 ratio correlated positively with the HRSD total score at both T0 and T1. At T0, a negative correlation was found between the Aβ40/Aβ42 ratio and the improvement of depressive and cognitive symptoms. Moreover, remitters (n = 9; HRSD ≤10) showed a significantly lower Aβ40/Aβ42 ratio at T0 than nonremitters. Conclusion: The present data suggest that a low Aβ40/Aβ42 ratio might characterize a subgroup of depressed patients who respond to ECT, while higher values of this parameter seem to be typical of more severe cases of patients with cognitive impairment.

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No correlation between time-linked plasma and CSF Aβ levels

Cited by 52 publications

References 28 publications

Importance and Impact of Preanalytical Variables on Alzheimer Disease Biomarker Concentrations in Cerebrospinal Fluid

Importance and Impact of Preanalytical Variables on Alzheimer Disease Biomarker Concentrations in Cerebrospinal Fluid

Plasma Aβ and PET PiB binding are inversely related in mild cognitive impairment

Plasma Amyloid-β Levels in Drug-Resistant Bipolar Depressed Patients Receiving Electroconvulsive Therapy

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