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- Gray, E., et al.
(författare)
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A multi-center study of neurofilament assay reliability and inter-laboratory variability
- 2020
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Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. - : Informa UK Limited. - 2167-8421 .- 2167-9223. ; 21:5-6, s. 452-458
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Significantly elevated levels of neurofilament light chain (NfL) and phosphorylated neurofilament heavy chain (pNfH) have been described in the blood and cerebrospinal fluid (CSF) of amyotrophic lateral sclerosis (ALS) patients. The aim of this study was to evaluate the analytical performance of different neurofilament assays in a round robin with 10 centers across Europe/U.S.Methods: Serum, plasma and CSF samples from a group of five ALS and five neurological control patients were distributed across 10 international specialist neurochemical laboratories for analysis by a range of commercial and in-house neurofilament assays. The performance of all assays was evaluated for their ability to differentiate between the groups. The inter-assay coefficient of variation was calculated where appropriate from sample measurements performed across multiple laboratories using the same assay.Results:All assays could differentiate ALS patients from controls in CSF. Inter-assay coefficient of variation of analytical platforms performed across multiple laboratories varied between 6.5% and 41.9%.Conclusions:This study is encouraging for the growing momentum toward integration of neurofilament measurement into the specialized ALS clinic. It demonstrates the importance of 'round robin' studies necessary to ensure the analytical quality required for translation to the routine clinical setting. A standardized neurofilament probe is needed which can be used as international benchmark for analytical performance in ALS.
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- Andreasson, Ulf, 1968, et al.
(författare)
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Assessing the commutability of candidate reference materials for the harmonization of neurofilament light measurements in blood
- 2023
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Ingår i: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter GmbH. - 1434-6621 .- 1437-4331. ; 61:7, s. 1245-1254
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Neurofilament light chain (NfL) concentration in blood is a biomarker of neuro-axonal injury in the nervous system and there now exist several assays with high enough sensitivity to measure NfL in serum and plasma. There is a need for harmonization with the goal of creating a certified reference material (CRM) for NfL and an early step in such an effort is to determine the best matrix for the CRM. This is done in a commutability study and here the results of the first one for NfL in blood is presented.Methods Forty paired individual serum and plasma samples were analyzed for NfL on four different analytical platforms. Neat and differently spiked serum and plasma were evaluated for their suitability as a CRM using the difference in bias approach.Results The correlation between the different platforms with regards to measured NfL concentrations were very high (Spearman's rho >= 0.96). Samples spiked with cerebrospinal fluid (CSF) showed higher commutability compared to samples spiked with recombinant human NfL protein and serum seems to be a better choice than plasma as the matrix for a CRM.Conclusions The results from this first commutability study on NfL in serum/plasma showed that it is feasible to create a CRM for NfL in blood and that spiking should be done using CSF rather than with recombinant human NfL protein.
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- Janelidze, Shorena, et al.
(författare)
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Plasma beta-amyloid in Alzheimer's disease and vascular disease
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Implementation of amyloid biomarkers in clinical practice would be accelerated if such biomarkers could be measured in blood. We analyzed plasma levels of A beta 42 and A beta 40 in a cohort of 719 individuals (the Swedish BioFINDER study), including patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI), Alzheimer's disease (AD) dementia and cognitively healthy elderly, using a ultrasensitive immunoassay (Simoa platform). There were weak positive correlations between plasma and cerebrospinal fluid (CSF) levels for both A beta 42 and A beta 40, and negative correlations between plasma A beta 42 and neocortical amyloid deposition (measured with PET). Plasma levels of A beta 42 and A beta 40 were reduced in AD dementia compared with all other diagnostic groups. However, during the preclinical or prodromal AD stages (i.e. in amyloid positive controls, SCD and MCI) plasma concentration of A beta 42 was just moderately decreased whereas A beta 40 levels were unchanged. Higher plasma (but not CSF) levels of A beta were associated with white matter lesions, cerebral microbleeds, hypertension, diabetes and ischemic heart disease. In summary, plasma A beta is overtly decreased during the dementia stage of AD indicating that prominent changes in A beta metabolism occur later in the periphery compared to the brain. Further, increased levels of A beta in plasma are associated with vascular disease.
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- Lazarev, Sergey, et al.
(författare)
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Influence of contacts and applied voltage on a structure of a single GaN nanowire
- 2021
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Ingår i: Applied Sciences (Switzerland). - : MDPI AG. - 2076-3417. ; 11:20
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Tidskriftsartikel (refereegranskat)abstract
- Semiconductor nanowires (NWs) have a broad range of applications for nano-and optoelectronics. The strain field of gallium nitride (GaN) NWs could be significantly changed when contacts are applied to them to form a final device, especially considering the piezoelectric properties of GaN. Investigation of influence of the metallic contacts on the structure of the NWs is of high importance for their applications in real devices. We have studied a series of different type of contacts and influence of the applied voltage bias on the contacted GaN NWs with the length of about 3 to 4 micrometers and with two different diameters of 200 nm and 350 nm. It was demonstrated that the NWs with the diameter of 200 nm are bend already by the interaction with the substrate. For all GaN NWs, significant structural changes were revealed after the contacts deposition. The results of our research may contribute to the future optoelectronic applications of the GaN nanowires.
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- Mielke, M. M., et al.
(författare)
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Comparison of Plasma Phosphorylated Tau Species With Amyloid and Tau Positron Emission Tomography, Neurodegeneration, Vascular Pathology, and Cognitive Outcomes
- 2021
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149. ; 78:9, s. 1108-1117
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Cerebrospinal fluid phosphorylated tau (p-tau) 181, p-tau217, and p-tau231 are associated with neuropathological outcomes, but a comparison of these p-tau isoforms in blood samples is needed. OBJECTIVE To conduct a head-to-head comparison of plasma p-tau181 and p-tau231 measured on the single-molecule array (Simoa) platform and p-tau181 and p-tau217 measured on the Meso Scale Discovery (MSD) platform on amyloid and tau positron emission tomography (PET) measures, neurodegeneration, vascular pathology, and cognitive outcomes. DESIGN, SETTING, AND PARTICIPANTS This study included data from the Mayo Clinic Study on Aging collected from March 1, 2015, to September 30, 2017, and analyzed between December 15, 2020, and May 17, 2021. Associations between the 4 plasma p-tau measures and dichotomous amyloid PET, metaregion of interest tau PET, and entorhinal cortex tau PET were analyzed using logistic regression models; the predictive accuracy was summarized using area under the receiver operating characteristic curve (AUROC) statistic. Of 1329 participants without dementia and with p-tau181 and p-tau217 on MSD, 200 participants with plasma p-tau181 and p-tau231 on Simoa and magnetic resonance imaging and amyloid and tau PET data at the same study visit were eligible. MAIN OUTCOMES AND MEASURES Primary outcomes included amyloid (greater than 1.48 standardized uptake value ratio) and tau PET, white matter hyperintensities, white matter microstructural integrity (fractional anisotropy genu of corpus callosum and hippocampal cingulum bundle), and cognition. RESULTS Of 200 included participants, 101 (50.5%) were male, and the median (interquartile range [IQR]) age was 79.5 (71.1-84.1) years. A total of 177 were cognitively unimpaired (CU) and 23 had mild cognitive impairment. Compared with amyloid-negative CU participants, among amyloid-positive CU participants, the median (IQR) Simoa p-tau181 measure was 49% higher (2.58 [2.00-3.72] vs 1.73 [1.45-2.13] pg/mL), MSD p-tau181 measure was 53% higher (1.22 [0.91-1.56] vs 0.80 [0.66-0.97] pg/mL), MSD p-tau217 measure was 77% higher (0.23 [0.17-0.34] vs 0.13 [0.09-0.18] pg/mL), and Simoa p-tau231 measure was 49% higher (20.21 [15.60-25.41] vs 14.27 [11.27-18.10] pg/mL). There were no differences between the p-tau species for amyloid PET and tau PET metaregions of interest. However, among CU participants, both MSD p-tau181 and MSD p-tau217 more accurately predicted abnormal entorhinal cortex tau PET than Simoa p-tau181 (MSD p-tau181: AUROC, 0.80 vs 0.70; P=.046; MSD p-tau217: AUROC, 0.81 vs 0.70; P=.04). MSD p-tau181 and p-tau217 and Simoa p-tau181, but not p-tau231, were associated with greater white matter hyperintensity volume and lower white matter microstructural integrity. CONCLUSIONS AND RELEVANCE In this largely presymptomatic population, these results suggest subtle differences across plasma p-tau species and platforms for the prediction of amyloid and tau PET and magnetic resonance imaging measures of cerebrovascular and Alzheimer-related pathology.
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- Nilsson, Johanna, 1993, et al.
(författare)
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Quantification of SNAP-25 with mass spectrometry and Simoa: a method comparison in Alzheimer's disease
- 2022
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Ingår i: Alzheimer's Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Synaptic dysfunction and degeneration are central to Alzheimer's disease (AD) and have been found to correlate strongly with cognitive decline. Thus, studying cerebrospinal fluid (CSF) biomarkers reflecting synaptic degeneration, such as the presynaptic protein synaptosomal-associated protein 25 (SNAP-25), is of importance to better understand the AD pathophysiology. Methods We compared a newly developed Single molecule array (Simoa) immunoassay for SNAP-25 with an in-house immunoprecipitation mass spectrometry (IP-MS) method in a well-characterized clinical cohort (n = 70) consisting of cognitively unimpaired (CU) and cognitively impaired (CI) individuals with and without A beta pathology (A beta+ and A beta-). Results A strong correlation (Spearman's rank correlation coefficient (r(s)) > 0.88; p < 0.0001) was found between the Simoa and IP-MS methods, and no statistically significant difference was found for their clinical performance to identify AD pathophysiology in the form of A beta pathology. Increased CSF SNAP-25 levels in CI A beta+ compared with CU A beta- (Simoa, p <= 0.01; IP-MS, p <= 0.05) and CI A beta- (Simoa, p <= 0.01; IP-MS, p <= 0.05) were observed. In independent blood samples (n = 32), the Simoa SNAP-25 assay was found to lack analytical sensitivity for quantification of SNAP-25 in plasma. Conclusions These results indicate that the Simoa SNAP-25 method can be used interchangeably with the IP-MS method for the quantification of SNAP-25 in CSF. Additionally, these results confirm that CSF SNAP-25 is increased in relation to amyloid pathology in the AD continuum.
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