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| 2. |
- Minikel, EV, et al.
(författare)
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Quantifying prion disease penetrance using large population control cohorts
- 2016
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Ingår i: Science translational medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6242 .- 1946-6234. ; 8:322, s. 322ra9-
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Tidskriftsartikel (refereegranskat)abstract
- Large genomic reference data sets reveal a spectrum of pathogenicity in the prion protein gene and provide genetic validation for a therapeutic strategy in prion disease.
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| 4. |
- Delaby, Constance, et al.
(författare)
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Clinical reporting following the quantification of cerebrospinal fluid biomarkers in Alzheimer's disease: An international overview.
- 2022
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Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 18:10, s. 1868-1879
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Tidskriftsartikel (refereegranskat)abstract
- The current practice of quantifying cerebrospinal fluid (CSF) biomarkers as an aid in the diagnosis of Alzheimer's disease (AD) varies from center to center. For a same biochemical profile, interpretation and reporting of results may differ, which can lead to misunderstandings and raises questions about the commutability of tests.We obtained a description of (pre-)analytical protocols and sample reports from 40 centers worldwide. A consensus approach allowed us to propose harmonized comments corresponding to the different CSF biomarker profiles observed in patients.The (pre-)analytical procedures were similar between centers. There was considerable heterogeneity in cutoff definitions and report comments. We therefore identified and selected by consensus the most accurate and informative comments regarding the interpretation of CSF biomarkers in the context of AD diagnosis.This is the first time that harmonized reports are proposed across worldwide specialized laboratories involved in the biochemical diagnosis of AD.
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| 5. |
- Erragued, R., et al.
(författare)
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Novel polyethersulfone mixed matrix adsorptive nanofiltration membrane fabricated from embedding zinc oxide coated by polyaniline
- 2023
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Ingår i: Journal of Environmental Chemical Engineering. - : Elsevier BV. - 2213-3437. ; 11:6
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Tidskriftsartikel (refereegranskat)abstract
- Novel mixed matrix polymeric membranes were prepared by incorporating self-produced zinc oxide coated by polyaniline (ZnO-PANI) nanoparticles into polyethersulfone (PES) matrix using phase inversion method. Nanoparticles were synthesized, characterized and incorporated in PES matrix with loadings from 0.05 to 0.6 wt%. ZnO-PANI demonstrated effectiveness as a low-cost adsorbent, especially at a loading of 0.2 wt%. ZnO-PANI was used for adsorbing total phenolic compounds (TPC) from olive leaf extract (OLE) at different initial adsorbate concentration (49.92–466.59 mg/L) and pH (2−6). ZnO-PANI proved to be an effective and low-cost adsorbent to remove TPC from OLE. Langmuir model described the adsorption of TPC better than Freundlich model. Effect of incorporated nanoparticles on membranes morphology and hydrophilic properties studied using contact angle measurement, water content, membrane pore size and porosity, SEM, FTIR and pure water flux. Prepared membranes showed a significant increment in porosity, pore size and hydrophilicity by addition of ZnO-PANI in the casting solution up to 0.2 wt%. This led to a considerable improvement in permeability, which decreased with higher additive concentration. During OLE filtration tests (10–30 bar) using bare PES and 0.2 wt% ZnO-PANI/PES membranes, 0.2 wt% ZnO-PANI/PES showed the highest permeate flux and good TPC rejection (83–87%). Bare PES exhibited impressive TPC value rejections (85–92%) and better fouling resistance. Using 0.2 wt% ZnO-PANI achieved a balanced permeate flux and TPC rejection. The research emphasizes the practical applicability of these membranes in various industries due to their enhanced efficacy in removing phenolic compounds from natural extracts, offering a balanced approach between permeate flux and TPC rejection.
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| 6. |
- Saddiki, H., et al.
(författare)
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Age and the association between apolipoprotein E genotype and Alzheimer disease: A cerebrospinal fluid biomarker-based case-control study
- 2020
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Ingår i: Plos Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 17:8
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Tidskriftsartikel (refereegranskat)abstract
- Background The epsilon 4 allele of apolipoprotein E (APOE) gene and increasing age are two of the most important known risk factors for developing Alzheimer disease (AD). The diagnosis of AD based on clinical symptoms alone is known to have poor specificity; recently developed diagnostic criteria based on biomarkers that reflect underlying AD neuropathology allow better assessment of the strength of the associations of risk factors with AD. Accordingly, we examined the global and age-specific association betweenAPOEgenotype and AD by using the A/T/N classification, relying on the cerebrospinal fluid (CSF) levels of beta-amyloid peptide (A, beta-amyloid deposition), phosphorylated tau (T, pathologic tau), and total tau (N, neurodegeneration) to identify patients with AD. Methods and findings This case-control study included 1,593 white AD cases (55.4% women; mean age 72.8 [range = 44-96] years) with abnormal values of CSF biomarkers from nine European memory clinics and the American Alzheimer's Disease Neuroimaging Initiative (ADNI) study. A total of 11,723 dementia-free controls (47.1% women; mean age 65.6 [range = 44-94] years) were drawn from two longitudinal cohort studies (Whitehall II and Three-City), in which incident cases of dementia over the follow-up were excluded from the control population. Odds ratio (OR) and population attributable fraction (PAF) for AD associated withAPOEgenotypes were determined, overall and by 5-year age categories. In total, 63.4% of patients with AD and 22.6% of population controls carried at least oneAPOE epsilon 4 allele. Compared with non-epsilon 4 carriers, heterozygous epsilon 4 carriers had a 4.6 (95% confidence interval 4.1-5.2;p< 0.001) and epsilon 4/epsilon 4 homozygotes a 25.4 (20.4-31.2;p< 0.001) higher OR of AD in unadjusted analysis. This association was modified by age (pfor interaction < 0.001). The PAF associated with carrying at least one epsilon 4 allele was greatest in the 65-70 age group (69.7%) and weaker before 55 years (14.2%) and after 85 years (22.6%). The protective effect ofAPOE epsilon 2 allele for AD was unaffected by age. Main study limitations are that analyses were based on white individuals and AD cases were drawn from memory centers, which may not be representative of the general population of patients with AD. Conclusions In this study, we found that AD diagnosis based on biomarkers was associated with APOE epsilon 4 carrier status, with a higher OR than previously reported from studies based on only clinical AD criteria. This association differs according to age, with the strongest effect at 65-70 years. These findings highlight the need for early interventions for dementia prevention to mitigate the effect ofAPOE epsilon 4 at the population level. Author summaryWhy was this study done? The epsilon 4 allele of apolipoprotein E () gene () and increasing age are two of the most important known risk factors for developing Alzheimer disease (AD). The recent development of diagnostic criteria based on biomarkers that reflect brain beta-amyloid and tau lesions (beta-amyloid deposition, pathologic tau, neurodegeneration [A/T/N] classification]) increases homogeneity in diagnosed cases. The strength of association of AD with risk factors can be better determined using biomarker-based AD compared with AD diagnosis based only on clinical criteria because the latter are known to lack specificity as a result of difficulties in ruling out other causes of dementia. What did the researchers do and find? We compared the overall and age-specific association between and AD using a case-control study that included 1,593 AD cases from memory clinics with positive cerebrospinal fluid biomarkers and 11,723 dementia-free controls drawn from two longitudinal cohort studies. The use of a large number of cases and controls allows assessment of whether the association between and AD is dependent on age. Compared with controls, patients with AD were more likely to carry one (odds ratio [OR] = 4.6) or two (OR = 25.3). This association was significantly modified by age, with the strongest association seen between 65 and 70 years of age and weaker associations at the two tails of the age distribution. What do these findings mean? Incorporating biomarkers for diagnosis of AD identified an association with that is apparently greater than has been previously reported using clinical diagnosis of the disease. The impact of on the risk of AD was strongest between the 65 and 70 years of age, earlier than the mean age at diagnosis in this study, which was 72.8 years.
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| 7. |
- Dumurgier, J., et al.
(författare)
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A Pragmatic, Data-Driven Method to Determine Cutoffs for CSF Biomarkers of Alzheimer Disease Based on Validation Against PET Imaging
- 2022
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 99:7
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives To elaborate a new algorithm to establish a standardized method to define cutoffs for CSF biomarkers of Alzheimer disease (AD) by validating the algorithm against CSF classification derived from PET imaging. Methods Low and high levels of CSF phosphorylated tau were first identified to establish optimal cutoffs for CSF beta-amyloid (A beta) peptide biomarkers. These A beta cutoffs were then used to determine cutoffs for CSF tau and phosphorylated tau markers. We compared this algorithm to a reference method, based on tau and amyloid PET imaging status (ADNI study), and then applied the algorithm to 10 large clinical cohorts of patients. Results A total of 6,922 patients with CSF biomarker data were included (mean [SD] age: 70.6 [8.5] years, 51.0% women). In the ADNI study population (n = 497), the agreement between classification based on our algorithm and the one based on amyloid/tau PET imaging was high, with Cohen's kappa coefficient between 0.87 and 0.99. Applying the algorithm to 10 large cohorts of patients (n = 6,425), the proportion of persons with AD ranged from 25.9% to 43.5%. Discussion The proposed novel, pragmatic method to determine CSF biomarker cutoffs for AD does not require assessment of other biomarkers or assumptions concerning the clinical diagnosis of patients. Use of this standardized algorithm is likely to reduce heterogeneity in AD classification.
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| 8. |
- Ishaq, I., et al.
(författare)
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Work in progress - establishing a master program in cyber physical systems : Basic findings and future perspectives
- 2019
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Ingår i: Proceedings - 2019 International Conference on Promising Electronic Technologies, ICPET 2019. - : Institute of Electrical and Electronics Engineers (IEEE). ; , s. 4-9
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Konferensbidrag (refereegranskat)abstract
- This paper reports on the basic findings and future perspectives of a capacity building project funded by the European Union. The International Master of Science on Cyber Physical Systems (MS@CPS) is a collaborative project that aims to establish a master program in cyber physical systems (CPS). A consortium composed of nine partners proposed the project. Three partners are European and from Germany, UK and Sweden; while the other six partners are from the South Mediterranean region and include: Palestine, Jordan and Tunisia. The consortium is led by the University of Siegen in Germany who also manages the implementation of the work packages. CPS is an emerging engineering subject with significant economic and societal implications, which motivated the consortium to propose the establishment of a master program to offer educational and training opportunities at graduate level in the fields of CPS. In this paper, CPS as a field of study is presented with an emphasis on its importance, especially with regard to meeting local needs. A brief description of the project is presented in conjunction with the methodology for developing the courses and their learning outcomes.
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| 11. |
- Vrillon, A., et al.
(författare)
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Plasma neuregulin 1 as a synaptic biomarker in Alzheimer's disease: a discovery cohort study
- 2022
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Ingår i: Alzheimers Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Synaptic dysfunction is an early core feature of Alzheimer's disease (AD), closely associated with cognitive symptoms. Neuregulin 1 (NRG1) is a growth and differentiation factor with a key role in the development and maintenance of synaptic transmission. Previous reports have shown that changes in cerebrospinal fluid (CSF) NRG1 concentration are associated with cognitive status and biomarker evidence of AD pathology. Plasma biomarkers reflecting synaptic impairment would be of great clinical interest. Objective To measure plasma NRG1 concentration in AD patients in comparison with other neurodegenerative disorders and neurological controls (NC) and to study its association with cerebrospinal fluid (CSF) core AD and synaptic biomarkers. Methods This retrospective study enrolled 127 participants including patients with AD at mild cognitive impairment stage (AD-MCI, n = 27) and at dementia stage (n = 35), non-AD dementia (n = 26, A beta-negative), non-AD MCI (n = 19), and neurological controls (n=20). Plasma and CSF NRG1, as well as CSF core AD biomarkers (A beta 42/A beta 40 ratio, phospho-tau, and total tau), were measured using ELISA. CSF synaptic markers were measured using ELISA for GAP-43 and neurogranin and through immunoprecipitation mass spectrometry for SNAP-25. Results Plasma NRG1 concentration was higher in AD-MCI and AD dementia patients compared with neurological controls (respectively P = 0.005 and P < 0.001). Plasma NRG1 differentiated AD MCI patients from neurological controls with an area under the curve of 88.3%, and AD dementia patients from NC with an area under the curve of 87.3%. Plasma NRG1 correlated with CSF NRG1 (beta = 0.372, P = 0.0056, adjusted on age and sex). Plasma NRG1 was associated with AD CSF core biomarkers in the whole cohort and in A beta-positive patients (beta = -0.197-0.423). Plasma NRG1 correlated with CSF GAP-43, neurogranin, and SNAP-25 (beta = 0.278-0.355). Plasma NRG1 concentration correlated inversely with MMSE in the whole cohort and in A beta-positive patients (all, beta = -0.188, P = 0.038; A beta+: beta = -0.255, P = 0.038). Conclusion Plasma NRG1 concentration is increased in AD patients and correlates with CSF core AD and synaptic biomarkers and cognitive status. Thus, plasma NRG1 is a promising non-invasive biomarker to monitor synaptic impairment in AD.
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