Levels of amyloid β peptide 42 (Aβ42), total tau, and phosphorylated tau-181 are well-established cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease, but variability in manual plate-based ...assays has limited their use. We examined the relationship between CSF biomarkers, as measured by a novel automated immunoassay platform, and amyloid positron emission tomography.
CSF samples from 200 individuals underwent separate analysis for Aβ42, total tau, and phosphorylated tau-181 with automated Roche Elecsys assays. Aβ40 was measured with a commercial plate-based assay. Positron emission tomography with Pittsburgh Compound B was performed less than 1 year from CSF collection.
Ratios of CSF biomarkers (total tau/Aβ42, phosphorylated tau-181/Aβ42, and Aβ42/Aβ40) best discriminated Pittsburgh Compound B–positive from Pittsburgh Compound B–negative individuals.
CSF biomarkers and amyloid positron emission tomography reflect different aspects of Alzheimer's disease brain pathology, and therefore, less-than-perfect correspondence is expected. Automated assays are likely to increase the utility of CSF biomarkers.
•Cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease were measured with the Roche Elecsys assays.•Total tau/Aβ42, phosphorylated tau-181/Aβ42, and Aβ42/Aβ40 best distinguished Pittsburgh Compound B positron emission tomography status.•All three CSF ratios were positive in 92% of Pittsburgh Compound B–positive individuals.•All three CSF ratios were negative in 81% of Pittsburgh Compound B–negative individuals.•CSF biomarkers may detect Alzheimer's disease pathology earlier than amyloid positron emission tomography.
Aim Several pathophysiological processes are involved in Parkinson's disease (PD) and could inform in vivo biomarkers. We assessed an established biomarker panel, validated in Alzheimer's Disease, in ...a PD cohort. Methods Longitudinal cerebrospinal fluid (CSF) samples from PPMI (252 PD, 115 healthy controls, HC) were analyzed at six timepoints (baseline, 6, 12, 24, 36, and 48 months follow-up) using Elecsys® electrochemiluminescence immunoassays to quantify neurofilament light chain (NfL), soluble TREM2 receptor (sTREM2), chitinase-3-like protein 1 (YKL40), glial fibrillary acidic protein (GFAP), interleukin-6 (IL-6), S100, and total alpha-synuclein (alphaSyn). Results alphaSyn was significantly lower in PD (mean 103 pg/ml vs. HC: 127 pg/ml, p0.05) and none showed a significant difference longitudinally. We found significantly higher levels of all these markers between PD patients who developed cognitive decline during follow-up, except for alphaSyn and IL-6. Conclusion Except for alphaSyn, the additional biomarkers did not differentiate PD and HC, and none showed longitudinal differences, but most markers predict cognitive decline in PD during follow-up.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
An Elecsys® Amyloid β (Aβ 1–42) immunoassay cutoff for classification of patients with Alzheimer's disease was investigated.
Cerebrospinal fluid samples collected from patients with mild-to-moderate ...Alzheimer's disease were analyzed by Elecsys® immunoassays: (1) Aβ (1–42), (2) total tau, and (3) phosphorylated tau. Cutoffs (Aβ 1–42 and ratios with tau) were estimated by method comparison between AlzBio3 (n = 206), mixture modeling (n = 216), and concordance with florbetapir F 18 imaging-based classification (n = 75).
A 1065-pg/mL (95% confidence interval: 985–1153) Elecsys® Aβ (1–42) cutoff provided 94% overall percentage agreement with AlzBio3. Comparable cutoff estimates (95% confidence interval) were derived from mixture modeling (equally weighted: 1017 949–1205 pg/mL; prevalence weighted: 1172 1081–1344 pg/mL) and concordance with florbetapir F 18 imaging (visual read: 1198 998–1591 pg/mL; automated: 1198 1051–1638 pg/mL).
Based on three approaches, a 1100-pg/mL Elecsys® Aβ (1–42) cutoff is suitable for clinical trials with similar populations and preanalytical handling.
•Biomarkers can facilitate appropriate patient recruitment into clinical trials.•Amyloid beta measurement can aid the identification of amyloid-positive patients.•Similar cutoff estimates were derived by three different approaches.
Differentially expressed and immunogenic spore proteins of the Bacillus cereus group of bacteria, which includes Bacillus anthracis, Bacillus cereus, and Bacillus thuringiensis, were identified. ...Comparative proteomic profiling of their spore proteins distinguished the three species from each other as well as the virulent from the avirulent strains. A total of 458 proteins encoded by 232 open reading frames were identified by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry analysis for all the species. A number of highly expressed proteins, including elongation factor Tu (EF-Tu), elongation factor G, 60-kDa chaperonin, enolase, pyruvate dehydrogenase complex, and others exist as charge variants on two-dimensional gels. These charge variants have similar masses but different isoelectric points. The majority of identified proteins have cellular roles associated with energy production, carbohydrate transport and metabolism, amino acid transport and metabolism, posttranslational modifications, and translation. Novel vaccine candidate proteins were identified using B. anthracis polyclonal antisera from humans postinfected with cutaneous anthrax. Fifteen immunoreactive proteins were identified in B. anthracis spores, whereas 7, 14, and 7 immunoreactive proteins were identified for B. cereus and in the virulent and avirulent strains of B. thuringiensis spores, respectively. Some of the immunodominant antigens include charge variants of EF-Tu, glyceraldehyde-3-phosphate dehydrogenase, dihydrolipoamide acetyltransferase, Δ-1-pyrroline-5-carboxylate dehydrogenase, and a dihydrolipoamide dehydrogenase. Alanine racemase and neutral protease were uniquely immunogenic to B. anthracis. Comparative analysis of the spore immunome will be of significance for further nucleic acid- and immuno-based detection systems as well as next-generation vaccine development.
Brucella abortus is the etiologic agent of bovine brucellosis and causes a chronic disease in humans known as undulant fever. In livestock the disease is characterized by abortion and sterility. ...Live, attenuated vaccines such as S19 and RB51 have been used to control the spread of the disease in animals; however, they are considered unsafe for human use and they induce abortion in pregnant cattle. For the development of a safer and equally efficacious vaccine, immunoproteomics was utilized to identify novel candidate proteins from B. abortus cell envelope (CE). A total of 163 proteins were identified using 2‐DE with MALDI‐TOF MS and LC‐MS/MS. Some of the major protein components include outer‐membrane protein (OMP) 25, OMP31, Omp2b porin, and 60 kDa chaperonin GroEL. 2‐DE Western blot analyses probed with antiserum from bovine and a human patient infected with Brucella identified several new immunogenic proteins such as fumarate reductase flavoprotein subunit, F0F1‐type ATP synthase α subunit, and cysteine synthase A. The elucidation of the immunome of B. abortus CE identified a number of candidate proteins for developing vaccines against Brucella infection in bovine and humans.
Background
We evaluated the Roche Elecsys® NeuroToolKit (NTK) assay panel of 12 cerebrospinal fluid (CSF) biomarkers in patients from a total of six clinical trials of crenezumab and gantenerumab in ...sporadic Alzheimer’s disease (AD), with respect to the correlations between individual biomarkers, and their associations with patient characteristics and disease severity. Additionally, we assessed their ability to measure and predict disease progression.
Method
CSF samples were collected at baseline and follow‐up (Phase II, 1.5 years; Phase III, 1 and 2 years) from a subset of patients enrolled in the Phase II ABBY (NCT01343966)/BLAZE (NCT01397578) studies of crenezumab in mild‐to‐moderate AD, the Phase III CREAD (NCT02670083)/CREAD 2 (NCT03114657) studies of crenezumab in prodromal‐to‐mild AD, the Phase III SCarlet RoAD (NCT01224106) study of gantenerumab in prodromal AD, and the Phase III Marguerite RoAD (NCT02051608) study of gantenerumab in mild AD. NTK assays included beta‐amyloid (1‐42), beta‐amyloid (1‐40), alpha‐synuclein, GFAP, IL‐6, neurogranin, neurofilament light chain (NfL), phospho‐Tau (181P), S100B, sTREM2, total Tau, and YKL‐40. Correlations between biomarkers, longitudinal changes in biomarkers, and correlation between baseline biomarker levels and cognitive progression were evaluated across all six studies.
Result
All biomarkers except IL‐6 positively correlated with each other; the highest correlations were between total Tau, phospho‐Tau (181P), and neurogranin (Spearman’s rho >0.9). NfL, GFAP, YKL‐40, and sTREM2 biomarkers positively correlated with patient age. Analyses of ABBY, BLAZE, CREAD, and CREAD2 showed consistent findings across all studies. Levels of NfL, GFAP, and α‐synuclein biomarkers increased at the 1 year and 1.5‐year timepoints. NfL correlated with disease severity and progression in the prodromal‐to‐mild population. Additionally, results from NTK measurements in SCarlet RoAD and Marguerite RoAD CSF samples will also be presented.
Conclusion
The NTK provided robust data and sufficient measuring range for the biomarkers tested. Further evaluation of these biomarkers is needed to understand their potential utility for clinical trials as pharmacodynamic biomarkers or for selecting patient populations. Elecsys is a trademark of Roche.
ZnO/Nylon 6 nanofiber mats were prepared by an electrospinning–electrospraying hybrid process in which ZnO nanoparticles were dispersed on the surface of Nylon 6 nanofibers without becoming ...completely embedded. The prepared ZnO/Nylon 6 nanofiber mats were evaluated for their abilities to kill bacteria or inhibit their growth and to catalytically detoxify chemicals. Results showed that these ZnO/Nylon 6 nanofiber mats had excellent antibacterial efficiency (99.99%) against both the Gram-negative Escherichia coli and Gram-positive Bacillus cereus bacteria. In addition, they exhibited good detoxifying efficiency (95%) against paraoxon, a simulant of highly toxic chemicals. ZnO/Nylon 6 nanofiber mats were also deposited onto nylon/cotton woven fabrics and the nanofiber mats did not significantly affect the moisture vapor transmission rates and air permeability values of the fabrics. Therefore, ZnO/Nylon 6 nanofiber mats prepared by the electrospinning–electrospraying hybrid process are promising material candidates for protective applications.
Magnesium (Mg)-based alloys have become an important category of materials that is attracting more and more attention due to their high potential use as orthopedic temporary implants. These alloys ...are a viable alternative to nondegradable metals implants in orthopedics. In this paper, a detailed overview covering alloy development and manufacturing techniques is described. Further, important attributes for Mg-based alloys involved in orthopedic implants fabrication, physiological and toxicological effects of each alloying element, mechanical properties, osteogenesis, and angiogenesis of Mg are presented. A section detailing the main biocompatible Mg-based alloys, with examples of mechanical properties, degradation behavior, and cytotoxicity tests related to in vitro experiments, is also provided. Special attention is given to animal testing, and the clinical translation is also reviewed, focusing on the main clinical cases that were conducted under human use approval.
PDF
