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      Effect of long-term storage in biobanks on cerebrospinal fluid biomarker Aβ 1-42, T-tau, and P-tau values

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          Abstract

          Introduction

          We studied the effect of long-term storage at −80°C on cerebrospinal fluid (CSF) biomarker levels. Our approach assumed consistency of mean biomarker levels in a homogenous Alzheimer's disease patient cohort over time.

          Methods

          We selected 148 Alzheimer's disease samples that had inclusion dates equally distributed over the years 2001 to 2013 from our biobank. The concentrations of CSF biomarkers, amyloid β 1–42 (Aβ 1–42), total tau (T-tau), and phosphorylated tau 181 (P-tau), were measured with one enzyme-linked immunosorbent assay lot. Results were compared with historical results obtained at biobank inclusion.

          Results

          Linear regression analyses showed that the levels of CSF biomarkers, Aβ 1–42, T-tau, and P-tau, were not related to storage time at −80°C (β = 0.015, 0.048, and 0.0016 pg/mL per day, not significant). However, the differences between remeasured concentrations of Aβ 1–42 and concentrations at biobank inclusion measured for more than 30 assay batches increased with increasing time difference.

          Discussion

          The levels of CSF biomarkers, Aβ 1–42, T-tau, and P-tau, did not significantly change during the maximum period of 12 years of storage at −80°C. Batch variation for Aβ 1–42 is a factor that should be controlled for when using historical cohorts.

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          Most cited references10

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          Use of amyloid-PET to determine cutpoints for CSF markers: A multicenter study.

          To define CSF β-amyloid 1-42 (Aβ42) cutpoints to detect cortical amyloid deposition as assessed by 11C-Pittsburgh compound B ([11C]PiB)-PET and to compare these calculated cutpoints with cutpoints currently used in clinical practice.
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            When Physics Meets Biology: Low and High-Velocity Penetration, Blunt Impact, and Blast Injuries to the Brain

            The incidence of traumatic brain injuries (TBI) in the US has reached epidemic proportions with well over 2 million new cases reported each year. TBI can occur in both civilians and warfighters, with head injuries occurring in both combat and non-combat situations from a variety of threats, including ballistic penetration, acceleration, blunt impact, and blast. Most generally, TBI is a condition in which physical loads exceed the capacity of brain tissues to absorb without injury. More specifically, TBI results when sufficient external force is applied to the head and is subsequently converted into stresses that must be absorbed or redirected by protective equipment. If the stresses are not sufficiently absorbed or redirected, they will lead to damage of extracranial soft tissue and the skull. Complex interactions and kinematics of the head, neck and jaw cause strains within the brain tissue, resulting in structural, anatomical damage that is characteristic of the inciting insult. This mechanical trauma then initiates a neuro-chemical cascade that leads to the functional consequences of TBI, such as cognitive impairment. To fully understand the mechanisms by which TBI occurs, it is critically important to understand the effects of the loading environments created by these threats. In the following, a review is made of the pertinent complex loading conditions and how these loads cause injury. Also discussed are injury thresholds and gaps in knowledge, both of which are needed to design improved protective systems.
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              Performance Evaluation of an Automated ELISA System for Alzheimer’s Disease Detection in Clinical Routine

              The variability of Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers undermines their full-fledged introduction into routine diagnostics and clinical trials. Automation may help to increase precision and decrease operator errors, eventually improving the diagnostic performance. Here we evaluated three new CSF immunoassays, EUROIMMUNtrademark amyloid-β 1-40 (Aβ1-40), amyloid-β 1-42 (Aβ1-42), and total tau (t-tau), in combination with automated analysis of the samples. The CSF biomarkers were measured in a cohort consisting of AD patients (n = 28), mild cognitive impairment (MCI, n = 77), and neurological controls (OND, n = 35). MCI patients were evaluated yearly and cognitive functions were assessed by Mini-Mental State Examination. The patients clinically diagnosed with AD and MCI were classified according to the CSF biomarkers profile following NIA-AA criteria and the Erlangen score. Technical evaluation of the immunoassays was performed together with the calculation of their diagnostic performance. Furthermore, the results for EUROIMMUN Aβ1-42 and t-tau were compared to standard immunoassay methods (INNOTESTtrademark). EUROIMMUN assays for Aβ1-42 and t-tau correlated with INNOTEST (r = 0.83, p < 0.001 for both) and allowed a similar interpretation of the CSF profiles. The Aβ1-42/Aβ1-40 ratio measured with EUROIMMUN was the best parameter for AD detection and improved the diagnostic accuracy of Aβ1-42 (area under the curve = 0.93). In MCI patients, the Aβ1-42/Aβ1-40 ratio was associated with cognitive decline and clinical progression to AD.The diagnostic performance of the EUROIMMUN assays with automation is comparable to other currently used methods. The variability of the method and the value of the Aβ1-42/Aβ1-40 ratio in AD diagnosis need to be validated in large multi-center studies.
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                Author and article information

                Contributors
                Journal
                Alzheimers Dement (Amst)
                Alzheimers Dement (Amst)
                Alzheimer's & Dementia : Diagnosis, Assessment & Disease Monitoring
                Elsevier
                2352-8729
                04 April 2017
                2017
                04 April 2017
                : 8
                : 45-50
                Affiliations
                [a ]Department of Neurology, Neurochemistry Laboratory, VU University Medical Center, Amsterdam, The Netherlands
                [b ]Department of Neurology, Alzheimer Center, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands
                [c ]Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands
                Author notes
                []Corresponding author. Tel.: +31-204443868; Fax: +31-204443857. e.willemse@ 123456vumc.nl
                Article
                S2352-8729(17)30020-9
                10.1016/j.dadm.2017.03.005
                5403783
                733f2c0a-85b0-4bff-bdcd-f4abbcb99dd5
                © 2017 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Categories
                Cerebrospinal Fluid Biomarkers

                alzheimer's disease,cerebrospinal fluid,biomarkers,amyloid β1–42,total tau,phosphorylated tau181,long-term storage,preanalytical variation,batch variation,elisa

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