| 1. |
|
|
| 2. |
- Morrow, A., et al.
(författare)
-
Cerebrospinal Fluid Sphingomyelins in Alzheimer's Disease, Neurodegeneration, and Neuroinflammation
- 2022
-
Ingår i: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 90:2, s. 667-680
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Sphingomyelin (SM) levels have been associated with Alzheimer's disease (AD), but the association direction has been inconsistent and research on cerebrospinal fluid (CSF) SMs has been limited by sample size, breadth of SMs examined, and diversity of biomarkers available. Objective: Here, we seek to build on our understanding of the role of SM metabolites in AD by studying a broad range of CSF SMs and biomarkers of AD, neurodegeneration, and neuroinflammation. Methods: Leveraging two longitudinal AD cohorts with metabolome-wide CSF metabolomics data (n = 502), we analyzed the relationship between the levels of 12 CSF SMs, and AD diagnosis and biomarkers of pathology, neurodegeneration, and neuroinflammation using logistic, linear, and linear mixed effects models. Results: No SMs were significantly associated with AD diagnosis, mild cognitive impairment, or amyloid biomarkers. Phosphorylated tau, neurofilament light, alpha-synuclein, neurogranin, soluble triggering receptor expressed on myeloid cells 2, and chitinase-3-like-protein 1 were each significantly, positively associated with at least 5 of the SMs. Conclusion: The associations between SMs and biomarkers of neurodegeneration and neuroinflammation, but not biomarkers of amyloid or diagnosis of AD, point to SMs as potential biomarkers for neurodegeneration and neuroinflammation that may not be AD-specific.
|
|
| 3. |
- Mistry, A. K., et al.
(författare)
-
The DESPEC setup for GSI and FAIR
- 2022
-
Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 1033, s. 166662-
-
Tidskriftsartikel (refereegranskat)abstract
- The DEcay SPECtroscopy (DESPEC) setup for nuclear structure investigations was developed and commissioned at GSI, Germany in preparation for a full campaign of experiments at the FRS and Super-FRS. In this paper, we report on the first employment of the setup in the hybrid configuration with the AIDA implanter coupled to the FATIMA LaBr3(Ce) fast-timing array, and high-purity germanium detectors. Initial results are shown from the first experiments carried out with the setup. An overview of the setup and function is discussed, including technical advancements along the path.
|
|
| 4. |
- Deming, Y., et al.
(författare)
-
Neuropathology-based APOE genetic risk score better quantifies Alzheimer's risk
- 2023
-
Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:8, s. 3406-3416
-
Tidskriftsartikel (refereegranskat)abstract
- IntroductionApolipoprotein E (APOE) epsilon 4-carrier status or epsilon 4 allele count are included in analyses to account for the APOE genetic effect on Alzheimer's disease (AD); however, this does not account for protective effects of APOE epsilon 2 or heterogeneous effect of epsilon 2, epsilon 3, and epsilon 4 haplotypes. MethodsWe leveraged results from an autopsy-confirmed AD study to generate a weighted risk score for APOE (APOE-npscore). We regressed cerebrospinal fluid (CSF) amyloid and tau biomarkers on APOE variables from the Wisconsin Registry for Alzheimer's Prevention (WRAP), Wisconsin Alzheimer's Disease Research Center (WADRC), and Alzheimer's Disease Neuroimaging Initiative (ADNI). ResultsThe APOE-npscore explained more variance and provided a better model fit for all three CSF measures than APOE epsilon 4-carrier status and epsilon 4 allele count. These findings were replicated in ADNI and observed in subsets of cognitively unimpaired (CU) participants. DiscussionThe APOE-npscore reflects the genetic effect on neuropathology and provides an improved method to account for APOE in AD-related analyses.
|
|
| 5. |
- Keck, Michaela Kristina, et al.
(författare)
-
Amplification of the PLAG-family genes—PLAGL1 and PLAGL2—is a key feature of the novel tumor type CNS embryonal tumor with PLAGL amplification
- 2023
-
Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 145:1, s. 49-69
-
Tidskriftsartikel (refereegranskat)abstract
- Pediatric central nervous system (CNS) tumors represent the most common cause of cancer-related death in children aged 0–14 years. They differ from their adult counterparts, showing extensive clinical and molecular heterogeneity as well as a challenging histopathological spectrum that often impairs accurate diagnosis. Here, we use DNA methylation-based CNS tumor classification in combination with copy number, RNA-seq, and ChIP-seq analysis to characterize a newly identified CNS tumor type. In addition, we report histology, patient characteristics, and survival data in this tumor type. We describe a biologically distinct pediatric CNS tumor type (n = 31 cases) that is characterized by focal high-level amplification and resultant overexpression of either PLAGL1 or PLAGL2, and an absence of recurrent genetic alterations characteristic of other pediatric CNS tumor types. Both genes act as transcription factors for a regulatory subset of imprinted genes (IGs), components of the Wnt/β-Catenin pathway, and the potential drug targets RET and CYP2W1, which are also specifically overexpressed in this tumor type. A derived PLAGL-specific gene expression signature indicates dysregulation of imprinting control and differentiation/development. These tumors occurred throughout the neuroaxis including the cerebral hemispheres, cerebellum, and brainstem, and were predominantly composed of primitive embryonal-like cells lacking robust expression of markers of glial or neuronal differentiation (e.g., GFAP, OLIG2, and synaptophysin). Tumors with PLAGL1 amplification were typically diagnosed during adolescence (median age 10.5 years), whereas those with PLAGL2 amplification were diagnosed during early childhood (median age 2 years). The 10-year overall survival was 66% for PLAGL1-amplified tumors, 25% for PLAGL2-amplified tumors, 18% for male patients, and 82% for female patients. In summary, we describe a new type of biologically distinct CNS tumor characterized by PLAGL1/2 amplification that occurs predominantly in infants and toddlers (PLAGL2) or adolescents (PLAGL1) which we consider best classified as a CNS embryonal tumor and which is associated with intermediate survival. The cell of origin and optimal treatment strategies remain to be defined.
|
|
| 6. |
- Nedić Vasiljević, Bojana, et al.
(författare)
-
Galvanic displacement of Co with Rh boosts hydrogen and oxygen evolution reactions in alkaline media
- 2023
-
Ingår i: Journal of Solid State Electrochemistry. - : Springer Nature. - 1432-8488 .- 1433-0768. ; 27:7, s. 1877-1887
-
Tidskriftsartikel (refereegranskat)abstract
- The growing energy crisis put an emphasis on the development of novel efficient energy conversion and storage systems. Here we show that surface modification of cobalt by a fast galvanic displacement with rhodium significantly affects the activity towards hydrogen (HER) and oxygen evolution reactions (OER) in alkaline media. After only 20 s of galvanic displacement, the HER overpotential is reduced by 0.16 V and OER overpotential by 0.06 V. This means that the predicted water splitting voltage is reduced from 2.03 V (clean Co anode and cathode) to 1.81 V at 10 mA cm−2 (Rh-exchanged Co electrode). During the galvanic displacement process, the surface roughness of the Co electrode does not suffer significant changes, which suggests an increase in the intrinsic catalytic activity. Density Functional Theory calculations show that the reactivity of the Rh-modified Co(0001) surface is modified compared to that of the clean Co(0001). In the case of HER, experimentally observed activity improvements are directly correlated to the weakening of the hydrogen-surface bond, confirming the beneficial role of Rh incorporation into the Co surface. Graphical abstract: [Figure not available: see fulltext.].
|
|
| 7. |
- Xu, Yuexuan, et al.
(författare)
-
Effect of Pathway-Specific Polygenic Risk Scores for Alzheimer's Disease (AD) on Rate of Change in Cognitive Function and AD-Related Biomarkers Among Asymptomatic Individuals.
- 2023
-
Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 94:4, s. 1587-1605
-
Tidskriftsartikel (refereegranskat)abstract
- Genetic scores for late-onset Alzheimer's disease (LOAD) have been associated with preclinical cognitive decline and biomarker variations. Compared with an overall polygenic risk score (PRS), a pathway-specific PRS (p-PRS) may be more appropriate in predicting a specific biomarker or cognitive component underlying LOAD pathology earlier in the lifespan.In this study, we leveraged longitudinal data from the Wisconsin Registry for Alzheimer's Prevention and explored changing patterns in cognition and biomarkers at various age points along six biological pathways.PRS and p-PRSs with and without APOE were constructed separately based on the significant SNPs associated with LOAD in a recent genome-wide association study meta-analysis and compared to APOE alone. We used a linear mixed-effects model to assess the association between PRS/p-PRSs and cognitive trajectories among 1,175 individuals. We also applied the model to the outcomes of cerebrospinal fluid biomarkers in a subset. Replication analyses were performed in an independent sample.We found p-PRSs and the overall PRS can predict preclinical changes in cognition and biomarkers. The effects of PRS/p-PRSs on rate of change in cognition, amyloid-β, and tau outcomes are dependent on age and appear earlier in the lifespan when APOE is included in these risk scores compared to when APOE is excluded.In addition to APOE, the p-PRSs can predict age-dependent changes in amyloid-β, tau, and cognition. Once validated, they could be used to identify individuals with an elevated genetic risk of accumulating amyloid-β and tau, long before the onset of clinical symptoms.
|
|
| 8. |
- Xu, Yuexuan, et al.
(författare)
-
Effect of Pathway-specific Polygenic Risk Scores for Alzheimer's Disease (AD) on Rate of Change in Cognitive Function and AD-related Biomarkers among Asymptomatic Individuals.
- 2023
-
Ingår i: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory.
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Genetic scores for late-onset Alzheimer's disease (LOAD) have been associated with preclinical cognitive decline and biomarker variations. Compared with an overall polygenic risk score (PRS), a pathway-specific PRS (p-PRS) may be more appropriate in predicting a specific biomarker or cognitive component underlying LOAD pathology earlier in the lifespan.In this study, we leveraged 10 years of longitudinal data from initially cognitively unimpaired individuals in the Wisconsin Registry for Alzheimer's Prevention and explored changing patterns in cognition and biomarkers at various age points along six biological pathways.PRS and p-PRSs with and without apolipoprotein E ( APOE ) were constructed separately based on the significant SNPs associated with LOAD in a recent genome-wide association study meta-analysis and compared to APOE alone. We used a linear mixed-effects model to assess the association between PRS/p-PRSs and global/domain-specific cognitive trajectories among 1,175 individuals. We also applied the model to the outcomes of cerebrospinal fluid biomarkers for beta-amyloid 42 (Aβ42), Aβ42/40 ratio, total tau, and phosphorylated tau in a subset. Replication analyses were performed in an independent sample.We found p-PRSs and the overall PRS can predict preclinical changes in cognition and biomarkers. The effects of p-PRSs/PRS on rate of change in cognition, beta-amyloid, and tau outcomes are dependent on age and appear earlier in the lifespan when APOE is included in these risk scores compared to when APOE is excluded.In addition to APOE , the p-PRSs can predict age-dependent changes in beta-amyloid, tau, and cognition. Once validated, they could be used to identify individuals with an elevated genetic risk of accumulating beta-amyloid and tau, long before the onset of clinical symptoms.
|
|
