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| 3. |
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| 4. |
- 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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| 5. |
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| 6. |
- 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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| 7. |
- 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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| 8. |
- 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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| 9. |
- 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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| 10. |
- 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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| 11. |
- O'Bryant, S. E., et al.
(författare)
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Comparing biological markers of Alzheimer's disease across blood fraction and platforms: Comparing apples to oranges
- 2016
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 3, s. 27-34
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: This study investigated the comparability of potential Alzheimer's disease (AD) biomarkers across blood fractions and assay platforms. Methods: Nonfasting serum and plasma samples from 300 participants (150 AD patients and 150 controls) were analyzed. Proteomic markers were obtained via electrochemiluminescence or Luminex technology. Comparisons were conducted via Pearson correlations. The relative importance of proteins within an AD diagnostic profile was examined using random forest importance plots. Results: On the Meso Scale Discovery multiplex platform, 10 of the 21 markers shared >50% of the variance across blood fractions (serum amyloid A R2 = 0.99, interleukin (IL)10 R2 = 0.95, fatty acid-binding protein (FABP) R2 = 0.94, I309 R2 = 0.94, IL-5 R2 = 0.94, IL-6 R2 = 0.94, eotaxin3 R2 = 0.91, IL-18 R2 = 0.87, soluble tumor necrosis factor receptor 1 R2 = 0.85, and pancreatic polypeptide R2 = 0.81). When examining protein concentrations across platforms, only five markers shared >50% of the variance (beta 2 microglobulin R2 = 0.92, IL-18 R2 = 0.80, factor VII R2 = 0.78, CRP R2 = 0.74, and FABP R2 = 0.70). Discussion: The current findings highlight the importance of considering blood fractions and assay platforms when searching for AD relevant biomarkers. © 2016 The Authors.
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| 12. |
- Brum, Wagner S., et al.
(författare)
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Biological variation estimates of Alzheimer's disease plasma biomarkers in healthy individuals
- 2024
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Ingår i: Alzheimer's and Dementia. - 1552-5260 .- 1552-5279. ; 20:2, s. 1284-1297
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Blood biomarkers have proven useful in Alzheimer's disease (AD) research. However, little is known about their biological variation (BV), which improves the interpretation of individual-level data. METHODS: We measured plasma amyloid beta (Aβ42, Aβ40), phosphorylated tau (p-tau181, p-tau217, p-tau231), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) in plasma samples collected weekly over 10weeks from 20 participants aged 40 to 60 years from the European Biological Variation Study. We estimated within- (CVI) and between-subject (CVG) BV, analytical variation, and reference change values (RCV). RESULTS: Biomarkers presented considerable variability in CVI and CVG. Aβ42/Aβ40 had the lowest CVI (≈ 3%) and p-tau181 the highest (≈ 16%), while others ranged from 6% to 10%. Most RCVs ranged from 20% to 30% (decrease) and 25% to 40% (increase). DISCUSSION: BV estimates for AD plasma biomarkers can potentially refine their clinical and research interpretation. RCVs might be useful for detecting significant changes between serial measurements when monitoring early disease progression or interventions. Highlights Plasma amyloid beta (Aβ42/Aβ40) presents the lowest between- and within-subject biological variation, but also changes the least in Alzheimer's disease (AD) patients versus controls. Plasma phosphorylated tau variants significantly vary in their within-subject biological variation, but their substantial fold-changes in AD likely limits the impact of their variability. Plasma neurofilament light chain and glial fibrillary acidic protein demonstrate high between-subject variation, the impact of which will depend on clinical context. Reference change values can potentially be useful in monitoring early disease progression and the safety/efficacy of interventions on an individual level. Serial sampling revealed that unexpectedly high values in heathy individuals can be observed, which urges caution when interpreting AD plasma biomarkers based on a single test result.
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| 14. |
- Gromada, Jesper, et al.
(författare)
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Neuronal calcium sensor-1 potentiates glucose-dependent exocytosis in pancreatic beta cells through activation of phosphatidylinositol 4-kinase beta
- 2005
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 102:29, s. 10303-8
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Tidskriftsartikel (refereegranskat)abstract
- Cytosolic free Ca2+ plays an important role in the molecular mechanisms leading to regulated insulin secretion by the pancreatic beta cell. A number of Ca2+-binding proteins have been implicated in this process. Here, we define the role of the Ca2+-binding protein neuronal Ca2+ sensor-1 (NCS-1) in insulin secretion. In pancreatic beta cells, NCS-1 increases exocytosis by promoting the priming of secretory granules for release and increasing the number of granules residing in the readily releasable pool. The effect of NCS-1 on exocytosis is mediated through an increase in phosphatidylinositol (PI) 4-kinase beta activity and the generation of phosphoinositides, specifically PI 4-phosphate and PI 4,5-bisphosphate. In turn, PI 4,5-bisphosphate controls exocytosis through the Ca2+-dependent activator protein for secretion present in beta cells. Our results provide evidence for an essential role of phosphoinositide synthesis in the regulation of glucose-induced insulin secretion by the pancreatic beta cell. We also demonstrate that NCS-1 and its downstream target, PI 4-kinase beta, are critical players in this process by virtue of their capacity to regulate the release competence of the secretory granules.
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| 15. |
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| 16. |
- Harder, Constantin, et al.
(författare)
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Optical Properties of Slot‐Die Coated Hybrid Colloid/Cellulose‐Nanofibril Thin Films
- 2023
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Ingår i: Advanced Optical Materials. - : Wiley. - 2162-7568 .- 2195-1071. ; 11:13
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Tidskriftsartikel (refereegranskat)abstract
- Correlating nanostructure and optical properties of thin hybrid films is the crucial ingredient for designing sustainable applications ranging from structural colors in anticounterfeiting to sensors. Here, the tailoring of the refractive index of hybrid cellulose nanofibril/water-dispersed colloidal ink thin films is presented. The authors apply scalable, layer-by-layer slot-die coating for preparing the cellulose nanofibril and hybrid thin films. Making use of the mobility of the polymer chains in the colloids upon annealing, the influence of the different colloid sizes and their glass transition temperature on the refractive index of the hybrid material is shown. The complex refractive indices of the thin films are characterized by spectroscopic ellipsometry and correlated to the different nanostructures of the thin films. The authors find that post-deposition annealing changes the colloidal nanostructure from particulate to agglomerates. Depending on the size of the colloids, imbibition of the colloids into the cellulose nanofibril template is observed. This scalable approach offers new avenues in structural color functional biomaterial hybrid layers.
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| 17. |
- Henriksen, Kim, et al.
(författare)
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The future of blood-based biomarkers for Alzheimer's disease.
- 2014
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Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 10:1, s. 115-131
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Tidskriftsartikel (refereegranskat)abstract
- Treatment of Alzheimer's disease (AD) is significantly hampered by the lack of easily accessible biomarkers that can detect disease presence and predict disease risk reliably. Fluid biomarkers of AD currently provide indications of disease stage; however, they are not robust predictors of disease progression or treatment response, and most are measured in cerebrospinal fluid, which limits their applicability. With these aspects in mind, the aim of this article is to underscore the concerted efforts of the Blood-Based Biomarker Interest Group, an international working group of experts in the field. The points addressed include: (1) the major challenges in the development of blood-based biomarkers of AD, including patient heterogeneity, inclusion of the "right" control population, and the blood-brain barrier; (2) the need for a clear definition of the purpose of the individual markers (e.g., prognostic, diagnostic, or monitoring therapeutic efficacy); (3) a critical evaluation of the ongoing biomarker approaches; and (4) highlighting the need for standardization of preanalytical variables and analytical methodologies used by the field.
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| 18. |
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| 19. |
- Mattsson, Niklas, et al.
(författare)
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Plasma tau in Alzheimer disease
- 2016
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Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 87:17, s. 1827-1835
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To test whether plasma tau is altered in Alzheimer disease (AD) and whether it is related to changes in cognition, CSF biomarkers of AD pathology (including β-amyloid [Aβ] and tau), brain atrophy, and brain metabolism. Methods: This was a study of plasma tau in prospectively followed patients with AD (n 179), patients with mild cognitive impairment (n 195), and cognitive healthy controls (n 189) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and cross-sectionally studied patients with AD (n 61), mild cognitive impairment (n 212), and subjective cognitive decline (n 174) and controls (n 274) from the Biomarkers for Identifying Neurodegenerative Disorders Early and Reliably (BioFINDER) study at Lund University, Sweden. A total of 1284 participants were studied. Associations were tested between plasma tau and diagnosis, CSF biomarkers, MRI measures, 18 fluorodeoxyglucose-PET, and cognition. Results: Higher plasma tau was associated with AD dementia, higher CSF tau, and lower CSF Aβ 42, but the correlations were weak and differed between ADNI and BioFINDER. Longitudinal analysis in ADNI showed significant associations between plasma tau and worse cognition, more atrophy, and more hypometabolism during follow-up. Conclusions: Plasma tau partly reflects AD pathology, but the overlap between normal aging and AD is large, especially in patients without dementia. Despite group-level differences, these results do not support plasma tau as an AD biomarker in individual people. Future studies may test longitudinal plasma tau measurements in AD.
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| 20. |
- Mattsson, Niklas, 1979, et al.
(författare)
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Reference measurement procedures for Alzheimer's disease cerebrospinal fluid biomarkers: definitions and approaches with focus on amyloid β42.
- 2012
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Ingår i: Biomarkers in medicine. - : Future Medicine Ltd. - 1752-0371 .- 1752-0363. ; 6:4, s. 409-17
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Tidskriftsartikel (refereegranskat)abstract
- Cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) are increasingly used in clinical settings, research and drug trials. However, their broad-scale use on different technology platforms is hampered by the lack of standardization at the level of sample handling, determination of concentrations of analytes and the absence of well-defined performance criteria for in vitro diagnostic or companion diagnostic assays, which influences the apparent concentration of the analytes measured and the subsequent interpretation of the data. There is a need for harmonization of CSF AD biomarker assays that can reliably, across centers, quantitate CSF biomarkers with high analytical precision, selectivity and stability over long time periods. In this position paper, we discuss reference procedures for the measurement of CSF AD biomarkers, especially amyloid β42 and tau. We describe possible technical approaches, focusing on a selected reaction monitoring mass spectrometry assay as a candidate reference method for quantification of CSF amyloid β42.
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| 21. |
- Mondello, Stefania, et al.
(författare)
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Circulating brain injury exosomal proteins following Moderate-to-Severe traumatic brain injury : temporal profile, outcome prediction and therapy implications
- 2020
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Ingår i: Cells. - : MDPI. - 2073-4409. ; 9:4
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Tidskriftsartikel (refereegranskat)abstract
- Brain injury exosomal proteins are promising blood biomarker candidates in traumatic brain injury (TBI). A better understanding of their role in the diagnosis, characterization, and management of TBI is essential for upcoming clinical implementation. In the current investigation, we aimed to explore longitudinal trajectories of brain injury exosomal proteins in blood of patients with moderate-to-severe TBI, and to evaluate the relation with the free-circulating counterpart and patient imaging and clinical parameters. Exosomal levels of glial (glial fibrillary acidic protein (GFAP)) and neuronal/axonal (ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), neurofilament light chain (NFL), and total-tau (t-tau)) proteins were measured in serum of 21 patients for up 5 days after injury using single molecule array (Simoa) technology. Group-based trajectory analysis was used to generate distinct temporal exosomal biomarker profiles. We found altered profiles of serum brain injury exosomal proteins following injury. The dynamics and levels of exosomal and related free-circulating markers, although correlated, showed differences. Patients with diffuse injury displayed higher acute exosomal NFL and GFAP concentrations in serum than those with focal lesions. Exosomal UCH-L1 profile characterized by acutely elevated values and a secondary steep rise was associated with early mortality (n = 2) with a sensitivity and specificity of 100%. Serum brain injury exosomal proteins yielded important diagnostic and prognostic information and represent a novel means to unveil underlying pathophysiology in patients with moderate-to-severe TBI. Our findings support their utility as potential tools to improve patient phenotyping in clinical practice and therapeutic trials.
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| 22. |
- O'Bryant, Sid E, et al.
(författare)
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Blood-based biomarkers in Alzheimer disease: Current state of the science and a novel collaborative paradigm for advancing from discovery to clinic.
- 2016
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Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 13:1, s. 45-58
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Tidskriftsartikel (refereegranskat)abstract
- The last decade has seen a substantial increase in research focused on the identification of blood-based biomarkers that have utility in Alzheimer's disease (AD). Blood-based biomarkers have significant advantages of being time- and cost-efficient as well as reduced invasiveness and increased patient acceptance. Despite these advantages and increased research efforts, the field has been hampered by lack of reproducibility and an unclear path for moving basic discovery toward clinical utilization. Here we reviewed the recent literature on blood-based biomarkers in AD to provide a current state of the art. In addition, a collaborative model is proposed that leverages academic and industry strengths to facilitate the field in moving past discovery only work and toward clinical use. Key resources are provided. This new public-private partnership model is intended to circumvent the traditional handoff model and provide a clear and useful paradigm for the advancement of biomarker science in AD and other neurodegenerative diseases.
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| 23. |
- O'Bryant, Sid E, et al.
(författare)
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Guidelines for the standardization of preanalytic variables for blood-based biomarker studies in Alzheimer's disease research.
- 2015
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Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 11:5, s. 549-560
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Tidskriftsartikel (refereegranskat)abstract
- The lack of readily available biomarkers is a significant hindrance toward progressing to effective therapeutic and preventative strategies for Alzheimer's disease (AD). Blood-based biomarkers have potential to overcome access and cost barriers and greatly facilitate advanced neuroimaging and cerebrospinal fluid biomarker approaches. Despite the fact that preanalytical processing is the largest source of variability in laboratory testing, there are no currently available standardized preanalytical guidelines. The current international working group provides the initial starting point for such guidelines for standardized operating procedures (SOPs). It is anticipated that these guidelines will be updated as additional research findings become available. The statement provides (1) a synopsis of selected preanalytical methods utilized in many international AD cohort studies, (2) initial draft guidelines/SOPs for preanalytical methods, and (3) a list of required methodological information and protocols to be made available for publications in the field to foster cross-validation across cohorts and laboratories.
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| 24. |
- Wilke, C., et al.
(författare)
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Correlations between serum and CSF pNfH levels in ALS, FTD and controls: A comparison of three analytical approaches
- 2019
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Ingår i: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter GmbH. - 1434-6621 .- 1437-4331. ; 57:10, s. 1556-1564
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Tidskriftsartikel (refereegranskat)abstract
- Phosphorylated neurofilament heavy (pNfH), a neuronal cytoskeleton protein, might provide a promising blood biomarker of neuronal damage in neurodegenerative diseases (NDDs). The best analytical approaches to measure pNfH levels and whether serum levels correlate with cerebrospinal fluid (CSF) levels in NDDs remain to be determined. We here compared analytical sensitivity and reliability of three novel analytical approaches (homebrew Simoa, commercial Simoa and ELISA) for quantifying pNfH in both CSF and serum in samples of amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and control subjects. While all three assays showed highly correlated CSF measurements, Simoa assays also yielded high between-assay correlations for serum measurements (± = 0.95). Serum levels also correlated strongly with CSF levels for Simoa-based measurements (both ± = 0.62). All three assays allowed distinguishing ALS from controls by increased CSF pNfH levels, and Simoa assays also by increased serum pNfH levels. pNfH levels were also increased in FTD. pNfH concentrations in CSF and, if measured by Simoa assays, in blood might provide a sensitive and reliable biomarker of neuronal damage, with good between-assay correlations. Serum pNfH levels measured by Simoa assays closely reflect CSF levels, rendering serum pNfH an easily accessible blood biomarker of neuronal damage in NDDs. ©2019 Walter de Gruyter GmbH, Berlin/Boston.
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