| 1. |
|
|
| 2. |
- de Rojas, I., et al.
(författare)
-
Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
|
|
| 3. |
|
|
| 4. |
- Kattge, Jens, et al.
(författare)
-
TRY plant trait database - enhanced coverage and open access
- 2020
-
Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
-
Tidskriftsartikel (refereegranskat)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
|
|
| 5. |
- Bhowal, S., et al.
(författare)
-
Development of collective structures over noncollective excitations in Nd-139
- 2011
-
Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 84:2
-
Tidskriftsartikel (refereegranskat)abstract
- High-spin states in Nd-139 were investigated using the reaction Zr-96(Ca-48,5n) at a beam energy of 195 MeV and gamma-ray coincidences were acquired with the Euroball spectrometer. Apart from several dipole bands at medium excitation energy, three quadrupole bands have been observed at high spin. Linking transitions connecting two of the high-spin bands to low-energy states have been observed. Calculations based on the cranked-Nilsson-Strutinsky formalism have been used to assign configurations for the high-spin quadrupole bands.
|
|
| 6. |
- Leguillon, R., et al.
(författare)
-
High-spin spectroscopy of Nd-140
- 2013
-
Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 88:1
-
Tidskriftsartikel (refereegranskat)abstract
- The population of the high-spin states in Nd-140 was investigated using the reaction Zr-96(Ca-48,4n). The results from two experiments, one with the EUROBALL array and one with the JUROGAM II + RITU + GREAT setup employing the recoil decay tagging technique, have been combined to develop a very detailed level scheme for Nd-140. Twelve bands of quadrupole transitions and eleven bands of dipole transitions were identified and their connections to low-lying states were established. Calculations using the cranked Nilsson-Strutinsky and the tilted axis cranking models were used to interpret the observed structures. The overall good agreement between the experimental results and the calculations assuming a triaxial shape of the nucleus strongly support the existence of a stable triaxial shape at high spins in this mass region.
|
|
| 7. |
- Petrache, C. M., et al.
(författare)
-
Triaxiality at high spins in Nd nuclei
- 2006
-
Ingår i: Physica Scripta. - 0031-8949. ; T125, s. 212-213
-
Tidskriftsartikel (refereegranskat)abstract
- The level structure of Nd-140(80) has been established up to spin 48 by in-beam gamma-ray spectroscopy using the Zr-96(Ca-48, 4n) reaction. High-fold gamma-ray coincidences were measured with the EUROBALL spectrometer. Twelve new rotational bands have been discovered at high spins, showing the change from a spherical single-particle behaviour at low spins to a deformed regime with stable triaxiality at high spins. Possible configurations are assigned to the observed bands on the basis of configuration-dependent cranked Nilsson-Strutinsky calculations.
|
|
| 8. |
- Zerrouki, T., et al.
(författare)
-
Shape evolution and magnetic rotation in Nd-141
- 2015
-
Ingår i: European Physical Journal A. Hadrons and Nuclei. - : Springer Science and Business Media LLC. - 1434-6001. ; 51:4
-
Tidskriftsartikel (refereegranskat)abstract
- The high-spin states in Nd-141 were investigated using the Zr-96(Ca-48, 3n) reaction and the EU-ROBALL array. The level scheme has been extended up to an excitation energy of around 16MeV and spin 81/2. Two new bands of dipole transitions and three bands presumably of quadrupole transitions were identified and their connections to low-lying states were established. Cranked Nilsson-Strutinsky and tilted axis cranking calculations are combined in the interpretation of the observed dipole bands. The high-spin bands with assigned quadrupole transitions are interpreted as triaxial bands, while the dipole bands appear in the calculations to exhibit a shape evolution from low-deformation triaxial to spherical shape. They can be classified as magnetic rotation, with transition probabilities that show the characteristic decrease with angular momentum caused by the shears mechanism.
|
|
| 9. |
- Gorska, M., et al.
(författare)
-
Nuclear Structure far off Stability - RISING Campaigns
- 2007
-
Ingår i: Acta Physica Polonica. Series B: Elementary Particle Physics, Nuclear Physics, Statistical Physics, Theory of Relativity, Field Theory. - 0587-4254. ; 38:4, s. 1219-1228
-
Tidskriftsartikel (refereegranskat)abstract
- Nuclear structure studies at CST attracted recently increased interest for the results of present activities as well as for the future project FAIR. A broad range of physics phenomena can be addressed by high-resolution in-beam gamma-ray spectroscopy experiments with radioactive beams offered within the Rare Isotopes Spectroscopic INvestigation at GSI (RISING) project. It combined the EUROBALL Ge-Cluster detectors, the MINIBALL Ce detectors, the HECTOR-BaF detectors, and the fragment separator FRS. The secondary beams produced at relativistic energies were used for Coulomb excitation or secondary fragmentation experiments to study projectile like nuclei by measuring de-excitation photons. The first results of the "fast beam campaign" is discussed in comparison to various shell model calculations. The discussion focuses on the N = 32, 34 sub-shell closure based on neutron rich Cr isotopes. Alternatively, the relativistic radioactive beams, both in their ground and isomeric states, were implanted and their decay could be investigated. The "stopped beam campaign" has started in October 2005 with a series of g-factor measurements. It continued from February 2006 with the next, configuration and the main goal of identification of new isomers and angular momentum population in fragmentation reactions.
|
|
| 10. |
- Nag, Somnath, et al.
(författare)
-
Collective and noncollective states in (120)Te
- 2012
-
Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 85:1
-
Tidskriftsartikel (refereegranskat)abstract
- High-spin states in (120)Te were populated in the reaction (80)Se((48)Ca, alpha 4n)(120)Te at a beam energy of 207 MeV and gamma-ray coincidences were measured using the Gammasphere spectrometer. The previously known level scheme is extended to higher spin and new interband transitions and side-feeding branches are established. Five highly deformed rotational bands, extending up to almost I = 50, are observed for the first time. The bands are compared with similar structures found recently in neighboring nuclei. The experimental results are interpreted within the framework of the cranked Nilsson-Strutinsky model. Configuration assignments to several terminating states and to the high-spin bands are discussed.
|
|
| 11. |
- Recchia, F, et al.
(författare)
-
Position resolution of the prototype AGATA triple-cluster detector from an in-beam experiment
- 2009
-
Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 604:3, s. 555-562
-
Tidskriftsartikel (refereegranskat)abstract
- AGATA belongs to a new generation of gamma-ray detector arrays for nuclear spectroscopy at present in its final stage of development. The detectors of these new arrays will be based on 36-fold electronically segmented coaxial germanium diodes operated in position sensitive mode. An in-beam test of the AGATA prototype triple cluster detector was carried out with the purpose of demonstrating the feasibility of such detectors and in order to measure the most sensitive parameters for their overall performance. An inverse kinematics reaction was performed, using a Ti-48 beam at an energy of 100MeV, impinging on a deuterated titanium tat-get. The results from the analysis of the experimental data, compared with the predictions of Monte Carlo Simulations, give an estimation of the position sensitivity of these detectors of about 5 mm FWHM, consistent with the specifications required. (C) 2009 Elsevier B.V. All rights reserved.
|
|
| 12. |
- Singh, Purnima, et al.
(författare)
-
High-spin rotational bands in I-123
- 2012
-
Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 86:6
-
Tidskriftsartikel (refereegranskat)abstract
- High-spin states in I-123 were populated in the reaction Se-80(Ca-48,p4n)I-123 at a beam energy of 207 MeV and gamma-ray coincidence events were measured using the Gammasphere spectrometer. Three weakly populated, high-spin rotational bands have been discovered with characteristics similar to those of the long collective bands recently observed in other nuclei of this mass region. Configuration assignments are proposed based on calculations within the framework of the cranked Nilsson-Strutinsky approach. DOI: 10.1103/PhysRevC.86.067305
|
|
| 13. |
- Nag, Somnath, et al.
(författare)
-
Revised level structure of Te-120
- 2014
-
Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 90:3
-
Tidskriftsartikel (refereegranskat)abstract
- The level scheme of the nucleus Te-120, populated in the reaction Se-80(Ca-48, alpha 4n), was reinvestigated using gamma-ray coincidence data measured with the Gammasphere spectrometer. Previously, five high-spin rotational bands were discovered in this nucleus. The present reinvestigation revealed that the decay of band b1 is more complex than suggested in the earlier work and that it cannot be uniquely determined. Furthermore, a number of new transitions are added to the level scheme. The implications for the spin assignments and excitation energies of the five bands and for comparisons with cranked Nilsson-Strutinsky calculations are discussed.
|
|
| 14. |
- Singh, Purnima, et al.
(författare)
-
Core excitations beyond maximally aligned configurations in I-123
- 2012
-
Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 85:3
-
Tidskriftsartikel (refereegranskat)abstract
- High-spin states in I-123 have been populated in the Se-80(Ca-48, p4n) I-123 reaction at 207 MeV and gamma-ray coincidence events have been recorded with the Gammasphere spectrometer. The level scheme of I-123 has been extended up to spin I = 63/2. The nucleus undergoes a shape transition from moderately deformed states with collective rotation at low spins to noncollective oblate configurations at higher spins. Maximally aligned terminating states involving all nine particles outside the Sn-114 core and states with one particle antialigned are identified. A large number of weak transitions feed the terminating states. Cranked Nilsson-Strutinsky calculations have been performed to determine possible configurations for the observed energy levels.
|
|
| 15. |
- Jansen, Iris E, et al.
(författare)
-
Genome-wide meta-analysis for Alzheimer's disease cerebrospinal fluid biomarkers.
- 2022
-
Ingår i: Acta neuropathologica. - : Springer Science and Business Media LLC. - 1432-0533 .- 0001-6322. ; 144:5, s. 821-842
-
Tidskriftsartikel (refereegranskat)abstract
- Amyloid-beta 42 (Aβ42) and phosphorylated tau (pTau) levels in cerebrospinal fluid (CSF) reflect core features of the pathogenesis of Alzheimer's disease (AD) more directly than clinical diagnosis. Initiated by the European Alzheimer & Dementia Biobank (EADB), the largest collaborative effort on genetics underlying CSF biomarkers was established, including 31 cohorts with a total of 13,116 individuals (discovery n=8074; replication n=5042 individuals). Besides the APOE locus, novel associations with two other well-established AD risk loci were observed; CR1 was shown a locus for Aβ42 and BIN1 for pTau. GMNC and C16orf95 were further identified as loci for pTau, of which the latter is novel. Clustering methods exploring the influence of all known AD risk loci on the CSF protein levels, revealed 4 biological categories suggesting multiple Aβ42 and pTau related biological pathways involved in the etiology of AD. In functional follow-up analyses, GMNC and C16orf95 both associated with lateral ventricular volume, implying an overlap in genetic etiology for tau levels and brain ventricular volume.
|
|
| 16. |
- Buck, M., et al.
(författare)
-
The LIVE program : Results of test L1 and joint analyses on transient molten pool thermal hydraulics
- 2010
-
Ingår i: Progress in nuclear energy (New series). - : Elsevier BV. - 0149-1970 .- 1878-4224. ; 52:1, s. 46-60
-
Tidskriftsartikel (refereegranskat)abstract
- The development of a corium pool in the lower head and its behaviour is still a critical issue. This concerns, in general, the understanding of a severe accident with core melting, its course, major critical phases and timing, and the influence of these processes on the accident progression as well as, in particular, the evaluation of in-vessel melt retention by external vessel flooding as an accident mitigation strategy. Previous studies were especially related to the in-vessel retention question and often just concentrated on the quasi-steady state behaviour of a large molten pool in the lower head, considered as a bounding configuration. However, non-feasibility of the in-vessel retention concept for high power density reactors and uncertainties e.g. due to layering effects even for low or medium power reactors, turns this to be insufficient. Rather, it is essential to consider the whole evolution of the accident, including e.g. formation and growth of the in-core melt pool, characteristics of corium arrival in the lower head, and molten pool behaviour after the debris re-melting. These phenomena have a strong impact on a potential termination of a severe accident. The general objective of the LIVE program at FZK is to study these phenomena resulting from core melting experimentally in large-scale 3D geometry and in supporting separate-effects tests, with emphasis on the transient behaviour. Up to now, several tests on molten pool behaviour have been performed within the LIVE experimental program with water and with non-eutectic melts (KNO3-NaNO3) as simulant fluids. The results of these experiments, performed in nearly adiabatic and in isothermal conditions, allow a direct comparison with findings obtained earlier in other experimental programs (SIMECO, ACOPO, BALI, etc.) and will be used for the assessment of the correlations derived for the molten pool behaviour. Complementary to other international programs with real corium melts, the results of the LIVE activities also provide data for a better understanding of in-core corium pool behaviour. The experimental results are being used for the development and validation of mechanistic models for the description of molten pool behaviour, In the present paper, a range of different models is used for post-test calculations and comparative analyses. This includes simplified, but fast running models implemented in the severe accident codes ASTEC and ATHLET-CD. Further, a computational tool developed at KTH (PECM model implemented in Fluent) is applied. These calculations are complemented by analyses with the CFD code CONV (thermal hydraulics of heterogeneous, viscous and heat-generating melts) which was developed at IBRAE (Nuclear Safety Institute of Russian Academy) within the RASPLAV project and was further improved within the ISTC 2936 Project.
|
|
| 17. |
- Magallon, D, et al.
(författare)
-
European expert network for the reduction of uncertainties in severe accident safety issues (EURSAFE)
- 2005
-
Ingår i: Nuclear Engineering and Design. - : Elsevier BV. - 0029-5493 .- 1872-759X. ; 235:2-4, s. 309-346
-
Tidskriftsartikel (refereegranskat)abstract
- EURSAFE thematic network was a concerted action in the sixth framework programme of the European Commission. It established a large consensus among the main actors in nuclear safety on the severe accident issues where large uncertainties still subsist. The conclusions were derived from a first-of-kind phenomena identification and ranking tables (PIRT) on all aspects of severe accident also realised in the frame of the project. Starting from a list of all severe accident phenomena containing approximately 1000 entries and established by the twenty partner organisations, 106 phenomena were retained eventually as both important for safety and still lacking sufficient knowledge. Ultimately, 21 research areas for addressing these phenomena regrouped according to their similarities were identified. A networking structure for implementing and executing the necessary research was proposed, which promotes integration and harmonisation of the different national programmes. A severe accident database structure was proposed to ensure preservation of experimental data and enhanced communication for data exchange and use for severe accident codes assessment. The final product, named EURSAFE, is a website network, http://asa2.jrc.it/eursafe, connecting nodes located at partner sites. As the result of an action involving R&D governmental institutions, regulatory bodies, nuclear industry, utilities and universities from six EU Member States (Finland, France, Germany, Spain, Sweden, UK) plus JRC, three European third countries (Czech Republic, Hungary, Switzerland), and USA, EURSAFE represents a significant step towards harmonisation and credibility of the approaches, and resolution of the remaining severe accident issues.
|
|
| 18. |
|
|
| 19. |
- Bainbridge, Wilma A., et al.
(författare)
-
Memorability of photographs in subjective cognitive decline and mild cognitive impairment : Implications for cognitive assessment
- 2019
-
Ingår i: Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring. - : Wiley. - 2352-8729. ; 11, s. 610-618
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Impaired long-term memory is a defining feature of mild cognitive impairment (MCI). We tested whether this impairment is item specific, limited to some memoranda, whereas some remain consistently memorable. Methods: We conducted item-based analyses of long-term visual recognition memory. Three hundred ninety-four participants (healthy controls, subjective cognitive decline [SCD], and MCI) in the multicentric DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE) were tested with images from a pool of 835 photographs. Results: We observed consistent memorability for images in healthy controls, SCD, and MCI, predictable by a neural network trained on another healthy sample. Looking at memorability differences between groups, we identified images that could successfully categorize group membership with higher success and a substantial image reduction than the original image set. Discussion: Individuals with SCD and MCI show consistent memorability for specific items, while other items show significant diagnosticity. Certain stimulus features could optimize diagnostic assessment, while others could support memory.
|
|
| 20. |
- Buddingh, Emilie P., et al.
(författare)
-
Tumor-Infiltrating Macrophages Are Associated with Metastasis Suppression in High-Grade Osteosarcoma: A Rationale for Treatment with Macrophage Activating Agents
- 2011
-
Ingår i: Clinical Cancer Research. - 1078-0432. ; 17:8, s. 2110-2119
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: High-grade osteosarcoma is a malignant primary bone tumor with a peak incidence in adolescence. Overall survival (OS) of patients with resectable metastatic disease is approximately 20%. The exact mechanisms of development of metastases in osteosarcoma remain unclear. Most studies focus on tumor cells, but it is increasingly evident that stroma plays an important role in tumorigenesis and metastasis. We investigated the development of metastasis by studying tumor cells and their stromal context. Experimental Design: To identify gene signatures playing a role in metastasis, we carried out genome-wide gene expression profiling on prechemotherapy biopsies of patients who did (n = 34) and patients who did not (n = 19) develop metastases within 5 years. Immunohistochemistry (IHC) was performed on pretreatment biopsies from 2 additional cohorts (n = 63 and n = 16) and corresponding postchemotherapy resections and metastases. Results: A total of 118/132 differentially expressed genes were upregulated in patients without metastases. Remarkably, almost half of these upregulated genes had immunological functions, particularly related to macrophages. Macrophage-associated genes were expressed by infiltrating cells and not by osteosarcoma cells. Tumor-associated macrophages (TAM) were quantified with IHC and associated with significantly better overall survival (OS) in the additional patient cohorts. Osteosarcoma samples contained both M1-(CD14/HLA-DR alpha positive) and M2-type TAMs (CD14/CD163 positive and association with angiogenesis). Conclusions: In contrast to most other tumor types, TAMs are associated with reduced metastasis and improved survival in high-grade osteosarcoma. This study provides a biological rationale for the adjuvant treatment of high-grade osteosarcoma patients with macrophage activating agents, such as muramyl tripeptide. Clin Cancer Res; 17(8); 2110-9. (C) 2011 AACR.
|
|
| 21. |
|
|
| 22. |
- Huber, Maria, et al.
(författare)
-
Metabolic correlates of dopaminergic loss in dementia with lewy bodies
- 2020
-
Ingår i: Movement Disorders. - : WILEY. - 0885-3185 .- 1531-8257. ; 35, s. 595-605
-
Tidskriftsartikel (refereegranskat)abstract
- Background Striatal dopamine deficiency and metabolic changes are well-known phenomena in dementia with Lewy bodies and can be quantified in vivo by I-123-Ioflupane brain single-photon emission computed tomography of dopamine transporter and F-18-fluorodesoxyglucose PET. However, the linkage between both biomarkers is ill-understood. Objective We used the hitherto largest study cohort of combined imaging from the European consortium to elucidate the role of both biomarkers in the pathophysiological course of dementia with Lewy bodies. Methods We compared striatal dopamine deficiency and glucose metabolism of 84 dementia with Lewy body patients and comparable healthy controls. After normalization of data, we tested their correlation by region-of-interest-based and voxel-based methods, controlled for study center, age, sex, education, and current cognitive impairment. Metabolic connectivity was analyzed by inter-region coefficients stratified by dopamine deficiency and compared to healthy controls. Results There was an inverse relationship between striatal dopamine availability and relative glucose hypermetabolism, pronounced in the basal ganglia and in limbic regions. With increasing dopamine deficiency, metabolic connectivity showed strong deteriorations in distinct brain regions implicated in disease symptoms, with greatest disruptions in the basal ganglia and limbic system, coincident with the pattern of relative hypermetabolism. Conclusions Relative glucose hypermetabolism and disturbed metabolic connectivity of limbic and basal ganglia circuits are metabolic correlates of dopamine deficiency in dementia with Lewy bodies. Identification of specific metabolic network alterations in patients with early dopamine deficiency may serve as an additional supporting biomarker for timely diagnosis of dementia with Lewy bodies. (c) 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
|
|
| 23. |
- Johansson, Annica, 1969, et al.
(författare)
-
Genetic association of CDC2 with cerebrospinal fluid tau in Alzheimer's disease
- 2005
-
Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 20:6, s. 367-374
-
Tidskriftsartikel (refereegranskat)abstract
- We have recently reported that a polymorphism in the cell division cycle <i>(CDC2) </i>gene, designated Ex6 + 7I/D, is associated with Alzheimer’s disease (AD). The <i>CDC2</i> gene is located on chromosome 10q21.1 close to the marker D10S1225 linked to AD. Active cdc2 accumulates in neurons containing neurofibrillary tangles (NFT), a process that can precede the formation of NFT. Therefore, <i>CDC2 </i>is a promising candidate susceptibility gene for AD. We investigated the possible effects of the <i>CDC2</i> polymorphism on cerebrospinal fluid (CSF) biomarkers in AD patients. <i>CDC2</i> genotypes were evaluated in relation to CSF protein levels of total tau, phospho-tau and β-amyloid<sub>(1–42)</sub> in AD patients and control individuals, and in relation to the amount of senile plaques and NFT in the frontal cortex and in the hippocampus in patients with autopsy-proven AD and controls. The <i>CDC2</i> Ex6 + 7I allele was associated with a gene dose-dependent increase of CSF total tau levels (F<sub>2, 626</sub> = 7.0, p = 0.001) and the homozygous <i>CDC2</i> Ex6 + 7II genotype was significantly more frequent among AD patients compared to controls (p = 0.006, OR = 1.57, 95% CI 1.13–2.17). Our results provide further evidence for an involvement of cdc2 in the pathogenesis of AD.
|
|
| 24. |
|
|
| 25. |
- Johansson, Annica, 1969, et al.
(författare)
-
Increased frequency of a new polymorphism in the cell division cycle 2 (cdc2) gene in patients with Alzheimer's disease and frontotemporal dementia.
- 2003
-
Ingår i: Neuroscience letters. - : Elsevier BV. - 0304-3940. ; 340:1, s. 69-73
-
Tidskriftsartikel (refereegranskat)abstract
- Recent studies show linkage between Alzheimer's disease (AD) and two loci on chromosome 10. The cell division cycle 2 (cdc2) gene is located close to one of the chromosome 10 markers, and is a candidate gene for AD since it is involved in the pathogenesis of AD. We sequenced coding exons and flanking intronic sequences and the promoter region on the cdc2 gene and found three new single nucleotide polymorphisms (SNPs). We analyzed 272 Caucasian AD cases, 160 controls and 70 cases with frontotemporal dementia (FTD) for these SNPs. Homozygosity for one of the SNPs (Ex6+7I/D) was more frequent in both AD and FTD cases than in controls. In the combined tauopathy (AD and FTD) group the odds ratio (OR) was 1.77 (95% CI 1.19-2.63) for the Ex6+7II genotype. Our findings suggest that the Ex6+7I allele is associated with tauopathies, both AD and FTD.
|
|
| 26. |
- Johansson, A, et al.
(författare)
-
Increased frequency of a new polymorphism in the cycle 2 (cdc2) gene in patients with Alzheimer's disease frontotemporal dementia
- 2003
-
Ingår i: Neuroscience Letters. - 0304-3940. ; 340:1, s. 69-73
-
Tidskriftsartikel (refereegranskat)abstract
- Recent studies show linkage between Alzheimer's disease (AD) and two loci on chromosome 10. The cell division cycle 2 (cdc2) gene is located close to one of the chromosome 10 markers, and is a candidate gene for AD since it is involved in the pathogenesis of AD. We sequenced coding exons and flanking intronic sequences and the promoter region on the cdc2 gene and found three new single nucleotide polymorphisms (SNPs). We analyzed 272 Caucasian AD cases, 160 controls and 70 cases with frontotemporal dementia (FTD) for these SNPs. Homozygosity for one of the SNPs (Ex6 + 7I/D) was more frequent in both AD and FTD cases than in controls. In the combined tauopathy (AD and FTD) group the odds ratio (OR) was 1.77 (95% CI 1.19-2.63) for the Ex6 + 7II genotype. Our findings suggest that the Ex6 + 7I allele is associated with tauopathies, both AD and FrD. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.
|
|
| 27. |
- Olsson, A, et al.
(författare)
-
Measurement of alpha- and beta-secretase cleaved amyloid precursor protein in cerebrospinal fluid from Alzheimer patients
- 2003
-
Ingår i: Experimental Neurology. - 0014-4886. ; 183, s. 74-
-
Tidskriftsartikel (refereegranskat)abstract
- One of the major histopathological hallmarks of Alzheimer's disease (AD) is redundant senile plaques mainly composed of beta-amyloid (Abeta) aggregates. Alternative cleavage of the amyloid precursor protein (APP), occurring in both normal and AD subjects, results in the generation and secretion of soluble APP (sAPP) and Abeta. We examined the cerebrospinal fluid (CSF) for alpha- and beta-secretase cleaved sAPP (alpha-sAPP and beta-sAPP) in 81 sporadic AD patients, 19 patients with mild cognitive impairment, and 42 healthy controls by using newly developed sandwich enzyme-linked immunosorbent assay methods. We found that neither the level of CSF-alpha-sAPP nor CSF-beta-sAPP differed between sporadic AD patients and healthy controls. These findings further support the conclusion that there is no change in APP expression in sporadic AD. However, the level of CSF-beta-sAPP was significantly increased in patients with mild cognitive impairment compared to controls. We also investigated the relationship between the CSF level of alphabeta-sAPP and Abeta(42) and the apoE epsilon4 (apoFA.) allele. Significantly lower levels of CSF-alpha-sAPP were found in AD patients possessing one or two apoE4 alleles than in those not possessing the apoE4 allele. Neither the levels of CSF-beta-sAPP nor CSF-Abeta(42) differed when comparing ApoE4 allele-positive with allele-negative individuals. (C) 2003 Elsevier Science (USA). All rights reserved.
|
|
| 28. |
- Shami, Annelie, et al.
(författare)
-
Glucocorticoid-induced tumour necrosis factor receptor family-related protein (GITR) drives atherosclerosis in mice and is associated with an unstable plaque phenotype and cerebrovascular events in humans
- 2020
-
Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 41:31, s. 2938-2948
-
Tidskriftsartikel (refereegranskat)abstract
- AIMS: GITR-a co-stimulatory immune checkpoint protein-is known for both its activating and regulating effects on T-cells. As atherosclerosis bears features of chronic inflammation and autoimmunity, we investigated the relevance of GITR in cardiovascular disease (CVD). METHODS AND RESULTS: GITR expression was elevated in carotid endarterectomy specimens obtained from patients with cerebrovascular events (n = 100) compared to asymptomatic patients (n = 93) and correlated with parameters of plaque vulnerability, including plaque macrophage, lipid and glycophorin A content, and levels of interleukin (IL)-6, IL-12, and C-C-chemokine ligand 2. Soluble GITR levels were elevated in plasma from subjects with CVD compared to healthy controls. Plaque area in 28-week-old Gitr-/-Apoe-/- mice was reduced, and plaques had a favourable phenotype with less macrophages, a smaller necrotic core and a thicker fibrous cap. GITR deficiency did not affect the lymphoid population. RNA sequencing of Gitr-/-Apoe-/- and Apoe-/- monocytes and macrophages revealed altered pathways of cell migration, activation, and mitochondrial function. Indeed, Gitr-/-Apoe-/- monocytes displayed decreased integrin levels, reduced recruitment to endothelium, and produced less reactive oxygen species. Likewise, GITR-deficient macrophages produced less cytokines and had a reduced migratory capacity. CONCLUSION: Our data reveal a novel role for the immune checkpoint GITR in driving myeloid cell recruitment and activation in atherosclerosis, thereby inducing plaque growth and vulnerability. In humans, elevated GITR expression in carotid plaques is associated with a vulnerable plaque phenotype and adverse cerebrovascular events. GITR has the potential to become a novel therapeutic target in atherosclerosis as it reduces myeloid cell recruitment to the arterial wall and impedes atherosclerosis progression.
|
|
| 29. |
- Stockbauer, Anna, et al.
(författare)
-
Metabolic network alterations as a supportive biomarker in dementia with Lewy bodies with preserved dopamine transmission
- 2024
-
Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : SPRINGER. - 1619-7070 .- 1619-7089. ; 51:4, s. 1023-1034
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose Metabolic network analysis of FDG-PET utilizes an index of inter-regional correlation of resting state glucose metabolism and has been proven to provide complementary information regarding the disease process in parkinsonian syndromes. The goals of this study were (i) to evaluate pattern similarities of glucose metabolism and network connectivity in dementia with Lewy bodies (DLB) subjects with subthreshold dopaminergic loss compared to advanced disease stages and to (ii) investigate metabolic network alterations of FDG-PET for discrimination of patients with early DLB from other neurodegenerative disorders (Alzheimer's disease, Parkinson's disease, multiple system atrophy) at individual patient level via principal component analysis (PCA).Methods FDG-PETs of subjects with probable or possible DLB (n = 22) without significant dopamine deficiency (z-score < 2 in putamen binding loss on DaT-SPECT compared to healthy controls (HC)) were scaled by global-mean, prior to volume-of-interest-based analyses of relative glucose metabolism. Single region metabolic changes and network connectivity changes were compared against HC (n = 23) and against DLB subjects with significant dopamine deficiency (n = 86). PCA was applied to test discrimination of patients with DLB from disease controls (n = 101) at individual patient level.Results Similar patterns of hypo- (parietal- and occipital cortex) and hypermetabolism (basal ganglia, limbic system, motor cortices) were observed in DLB patients with and without significant dopamine deficiency when compared to HC. Metabolic connectivity alterations correlated between DLB patients with and without significant dopamine deficiency (R2 = 0.597, p < 0.01). A PCA trained by DLB patients with dopamine deficiency and HC discriminated DLB patients without significant dopaminergic loss from other neurodegenerative parkinsonian disorders at individual patient level (area-under-the-curve (AUC): 0.912).Conclusion Disease-specific patterns of altered glucose metabolism and altered metabolic networks are present in DLB subjects without significant dopaminergic loss. Metabolic network alterations in FDG-PET can act as a supporting biomarker in the subgroup of DLB patients without significant dopaminergic loss at symptoms onset.
|
|
