| 1. |
- Engström, Åsa, et al.
(författare)
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Losing the identity of a hockey player : the long-term effects of concussions
- 2020
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Ingår i: Concussion. - : Future Medicine. - 2056-3299. ; 5:2
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To describe what suffering multiple concussions meant for former semi-professional or professional hockey players who were forced to end their career. Results: Nine former Swedish hockey players, who once played on national or professional teams were interviewed. The interviews were analyzed with reference to hermeneutic phenomenology to interpret and explain their experiences. The theme of losing one’s identity as a hockey player was constructed from five subthemes: being limited in everyday life, returning to the hockey stadium as soon as possible, forming a post career identity, lacking understanding and support, and preventing injuries by respecting other players. Conclusion: The former hockey players struggled with developing their off-the-ice identities and with finding other sources of meaning for their lives.Lay abstractDespite considerable attention to improving the initial management of concussions suffered by hockey players, few studies have examined their long-term effects. In response, the study reported here aimed to describe what suffering multiple concussions meant for former semi-professional or professional hockey players who were forced to end their career. Nine former Swedish hockey players, who once played on national or professional teams were interviewed and the interviews were analyzed in order to interpret and explain their experiences. The overall theme was formulated as losing one’s identity as a hockey player. In conclusion, the former hockey players seem to struggle with developing their off-the-ice identities and with finding other sources of meaning for their lives.
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| 2. |
- Sandin, Linnea, et al.
(författare)
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Beneficial effects of increased lysozyme levels in Alzheimer’s disease modelled in Drosophila melanogaster
- 2016
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Ingår i: The FEBS Journal. - : John Wiley & Sons. - 1742-464X .- 1742-4658. ; 283:19, s. 3508-3522
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Tidskriftsartikel (refereegranskat)abstract
- Genetic polymorphisms of immune genes that associate with higher risk to develop Alzheimer’s disease (AD) have led to an increased research interest on the involvement of the immune system in AD pathogenesis. A link between amyloid pathology and immune gene expression was suggested in a genome-wide gene expression study of transgenic amyloid mouse models. In this study, the gene expression of lysozyme, a major player in the innate immune system, was found to be increased in a comparable pattern as the amyloid pathology developed in transgenic mouse models of AD. A similar pattern was seen at protein levels of lysozyme in human AD brain and CSF, but this lysozyme pattern was not seen in a tau transgenic mouse model. Lysozyme was demonstrated to be beneficial for different Drosophila melanogaster models of AD. In flies that expressed Aβ1-42 or AβPP together with BACE1 in the eyes, the rough eye phenotype indicative of toxicity was completely rescued by coexpression of lysozyme. In Drosophila flies bearing the Aβ1-42 variant with the Arctic gene mutation, lysozyme increased the fly survival and decreased locomotor dysfunction dose dependently. An interaction between lysozyme and Aβ1-42 in the Drosophila eye was discovered. We propose that the increased levels of lysozyme, seen in mouse models of AD and in human AD cases, were triggered by Aβ1-42 and caused a beneficial effect by binding of lysozyme to toxic species of Aβ1-42, which prevented these from exerting their toxic effects. These results emphasize the possibility of lysozyme as biomarker and therapeutic target for AD.
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| 3. |
- Palmqvist, Sebastian, et al.
(författare)
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Detailed comparison of amyloid PET and CSF biomarkers for identifying early Alzheimer disease
- 2015
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Ingår i: Neurology. - : Lippincott Williams & Wilkins. - 1526-632X .- 0028-3878. ; 85:14, s. 1240-1249
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Tidskriftsartikel (refereegranskat)abstract
- Objective:To compare the diagnostic accuracy of CSF biomarkers and amyloid PET for diagnosing early-stage Alzheimer disease (AD).Methods:From the prospective, longitudinal BioFINDER study, we included 122 healthy elderly and 34 patients with mild cognitive impairment who developed AD dementia within 3 years (MCI-AD). -Amyloid (A) deposition in 9 brain regions was examined with [F-18]-flutemetamol PET. CSF was analyzed with INNOTEST and EUROIMMUN ELISAs. The results were replicated in 146 controls and 64 patients with MCI-AD from the Alzheimer's Disease Neuroimaging Initiative study.Results:The best CSF measures for identifying MCI-AD were A42/total tau (t-tau) and A42/hyperphosphorylated tau (p-tau) (area under the curve [AUC] 0.93-0.94). The best PET measures performed similarly (AUC 0.92-0.93; anterior cingulate, posterior cingulate/precuneus, and global neocortical uptake). CSF A42/t-tau and A42/p-tau performed better than CSF A42 and A42/40 (AUC difference 0.03-0.12, p < 0.05). Using nonoptimized cutoffs, CSF A42/t-tau had the highest accuracy of all CSF/PET biomarkers (sensitivity 97%, specificity 83%). The combination of CSF and PET was not better than using either biomarker separately.Conclusions:Amyloid PET and CSF biomarkers can identify early AD with high accuracy. There were no differences between the best CSF and PET measures and no improvement when combining them. Regional PET measures were not better than assessing the global A deposition. The results were replicated in an independent cohort using another CSF assay and PET tracer. The choice between CSF and amyloid PET biomarkers for identifying early AD can be based on availability, costs, and doctor/patient preferences since both have equally high diagnostic accuracy.Classification of evidence:This study provides Class III evidence that amyloid PET and CSF biomarkers identify early-stage AD equally accurately.
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| 4. |
- Schöll, Michael, 1980, et al.
(författare)
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Biomarkers for tau pathology.
- 2019
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Ingår i: Molecular and cellular neurosciences. - : Elsevier BV. - 1095-9327 .- 1044-7431. ; 97, s. 18-33
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Forskningsöversikt (refereegranskat)abstract
- The aggregation of fibrils of hyperphosphorylated and C-terminally truncated microtubule-associated tau protein characterizes 80% of all dementia disorders, the most common neurodegenerative disorders. These so-called tauopathies are hitherto not curable and their diagnosis, especially at early disease stages, has traditionally proven difficult. A keystone in the diagnosis of tauopathies was the development of methods to assess levels of tau protein in vivo in cerebrospinal fluid, which has significantly improved our knowledge about these conditions. Tau proteins have also been measured in blood, but the importance of tau-related changes in blood is still unclear. The recent addition of positron emission tomography ligands to visualize, map and quantify tau pathology has further contributed with information about the temporal and spatial characteristics of tau accumulation in the living brain. Together, the measurement of tau with fluid biomarkers and positron emission tomography constitutes the basis for a highly active field of research. This review describes the current state of biomarkers for tau biomarkers derived from neuroimaging and from the analysis of bodily fluids and their roles in the detection, diagnosis and prognosis of tau-associated neurodegenerative disorders, as well as their associations with neuropathological findings, and aims to provide a perspective on how these biomarkers might be employed prospectively in research and clinical settings.
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| 5. |
- Wang, Hao, 1975, et al.
(författare)
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Genome-scale metabolic network reconstruction of model animals as a platform for translational research
- 2021
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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. ; 118:30
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Tidskriftsartikel (refereegranskat)abstract
- Genome-scale metabolic models (GEMs) are used extensively for analysis of mechanisms underlying human diseases and metabolic malfunctions. However, the lack of comprehensive and high-quality GEMs for model organisms restricts translational utilization of omics data accumulating from the use of various disease models. Here we present a unified platform of GEMs that covers five major model animals, including Mouse1 (Mus musculus), Rat1 (Rattus norvegicus), Zebrafish1 (Danio rerio), Fruitfly1 (Drosophila melanogaster), and Worm1 (Caenorhabditis elegans). These GEMs represent the most comprehensive coverage of the metabolic network by considering both orthology-based pathways and species-specific reactions. All GEMs can be interactively queried via the accompanying web portal Metabolic Atlas. Specifically, through integrative analysis of Mouse1 with RNA-sequencing data from brain tissues of transgenic mice we identified a coordinated up-regulation of lysosomal GM2 ganglioside and peptide degradation pathways which appears to be a signature metabolic alteration in Alzheimer’s disease (AD) mouse models with a phenotype of amyloid precursor protein overexpression. This metabolic shift was further validated with proteomics data from transgenic mice and cerebrospinal fluid samples from human patients. The elevated lysosomal enzymes thus hold potential to be used as a biomarker for early diagnosis of AD. Taken together, we foresee that this evolving open-source platform will serve as an important resource to facilitate the development of systems medicines and translational biomedical applications.
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| 6. |
- Janelidze, Shorena, et al.
(författare)
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Increased blood-brain barrier permeability is associated with dementia and diabetes but not amyloid pathology or APOE genotype
- 2017
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 51, s. 104-112
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Tidskriftsartikel (refereegranskat)abstract
- Blood-brain barrier (BBB) dysfunction might be an important component of many neurodegenerative disorders. In this study, we investigated its role in dementia using large clinical cohorts. The cerebrospinal fluid (CSF)/plasma albumin ratio (Qalb), an indicator of BBB (and blood-CSF barrier) permeability, was measured in a total of 1015 individuals. The ratio was increased in patients with Alzheimer's disease, dementia with Lewy bodies or Parkinson's disease dementia, subcortical vascular dementia, and frontotemporal dementia compared with controls. However, this measure was not changed during preclinical or prodromal Alzheimer's disease and was not associated with amyloid positron emission tomography or APOE genotype. The Qalb was increased in diabetes mellitus and correlated positively with CSF bio-markers of angiogenesis and endothelial dysfunction (vascular endothelial growth factor, intracellular adhesion molecule 1, and vascular cell adhesion molecule 1). In healthy elderly, high body mass index and waist-hip ratio predicted increased Qalb 20 years later. In summary, BBB permeability is increased in major dementia disorders but does not relate to amyloid pathology or APOE genotype. Instead, BBB impairment may be associated with diabetes and brain microvascular damage. (C) 2016 The Authors. Published by Elsevier Inc.
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| 7. |
- Michno, Wojciech, 1992, et al.
(författare)
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Multimodal Chemical Imaging of Amyloid Plaque Polymorphism Reveals A beta Aggregation Dependent Anionic Lipid Accumulations and Metabolism
- 2018
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 90:13, s. 8130-8138
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Tidskriftsartikel (refereegranskat)abstract
- Amyloid plaque formation constitutes one of the main pathological hallmarks of Alzheimer's disease (AD) and is suggested to be a critical factor driving disease pathogenesis. Interestingly, in patients that display amyloid pathology but remain cognitively normal, A beta deposits are predominantly of diffuse morphology suggesting that cored plaque formation is primarily associated with cognitive deterioration and AD pathogenesis. Little is known about the molecular mechanism responsible for conversion of monomeric A beta into neurotoxic aggregates and the predominantly cored deposits observed in AD. The structural diversity among A beta plaques, including cored/compact- and diffuse, may be linked to their distinct A beta profile and other chemical species including neuronal lipids. We developed a novel, chemical imaging paradigm combining matrix assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) and fluorescent amyloid staining. This multimodal imaging approach was used to probe the lipid chemistry associated with structural plaque heterogeneity in transgenic AD mice (tgAPP(Swe)) and was correlated to A beta profiles determined by subsequent laser microdissection and immunoprecipitation-mass spectrometry. Multivariate image analysis revealed an inverse localization of ceramides and their matching metabolites to diffuse and cored structures within single plaques, respectively. Moreover, phosphatidylinositols implicated in AD pathogenesis, were found to localize to the diffuse A beta structures and correlate with A beta 1-42. Further, lysophospholipids implicated in neuroinflammation were increased in all A beta deposits. The results support previous clinical findings on the importance of lipid disturbances in AD pathophysiology and associated sphingolipid processing. These data highlight the potential of multimodal imaging as a powerful technology to probe neuropathological mechanisms.
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| 8. |
- Pikwer, Andreas, et al.
(författare)
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Effects of surgery and propofol-remifentanil total intravenous anesthesia on cerebrospinal fluid biomarkers of inflammation, Alzheimer's disease, and neuronal injury in humans: a cohort study
- 2017
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Ingår i: Journal of Neuroinflammation. - : Springer Science and Business Media LLC. - 1742-2094. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Background: Surgery and anesthesia have been linked to postoperative cognitive disturbance and increased risk of Alzheimer's disease. It is not clear by which mechanisms this increased risk for cognitive disease is mediated. Further, amyloid beta production has been suggested to depend on the sleep-wake cycle and neuronal activity. The aim of the present study was to examine if cerebrospinal fluid (CSF) concentrations of a number of biomarkers for Alzheimer's disease-related processes, including amyloid beta, neuronal injury, and inflammation, changed over time during intravenous anesthesia in surgical patients. Methods: We included patients scheduled for hysterectomy via laparotomy during general anesthesia with intravenous propofol and remifentanil. CSF samples were obtained before, during, and after surgery (5 h after induction) and tested for 27 biomarkers. Changes over time were tested with linear mixed effects models. Results: A total of 22 patients, all females, were included. The mean age was 50 years (+/- 9 SD). The mean duration of the anesthesia was 145 min (+/- 40 SD). Interleukin (IL)-6, IL-8, monocyte chemoattractant protein 1, and vascular endothelial growth factor A increased over time. IL-15 and IL-7 decreased slightly over time. Macrophage inflammatory protein 1 beta and placental growth factor also changed significantly. There were no significant effects on amyloid beta (A beta) or tau biomarkers. Conclusions: Surgery and general anesthesia with intravenous propofol and remifentanil induce, during and in the short term after the procedure, a neuroinflammatory response which is dominated by monocyte attractants, without biomarker signs of the effects on Alzheimer's disease pathology or neuronal injury.
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| 9. |
- Kaya, Ibrahim, et al.
(författare)
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Shedding Light on the Molecular Pathology of Amyloid Plaques in Transgenic Alzheimer's Disease Mice Using Multimodal MALDI Imaging Mass Spectrometry
- 2018
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Ingår i: ACS Chemical Neuroscience. - : American Chemical Society (ACS). - 1948-7193. ; 9:7, s. 1802-1817
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Tidskriftsartikel (refereegranskat)abstract
- Senile plaques formed by aggregated amyloid beta peptides are one of the major pathological hallmarks of Alzheimers disease (AD) which have been suggested to be the primary influence triggering the AD pathogenesis and the rest of the disease process. However, neurotoxic A beta aggregation and progression are associated with a wide range of enigmatic biochemical, biophysical and genetic processes. MALDI imaging mass spectrometry (IMS) is a label-free method to elucidate the spatial distribution patterns of intact molecules in biological tissue sections. In this communication, we utilized multimodal MALDI-IMS analysis on 18 month old transgenic AD mice (tgArcSwe) brain tissue sections to enhance molecular information correlated to individual amyloid aggregates on the very same tissue section. Dual polarity MALDI-IMS analysis of lipids on the same pixel points revealed high throughput lipid molecular information including sphingolipids, phospholipids, and lysophospholipids which can be correlated to the ion images of individual amyloid beta peptide isoforms at high spatial resolutions (10 mu m). Further, multivariate image analysis was applied in order to probe the multimodal MALDI-IMS data in an unbiased way which verified the correlative accumulations of lipid species with dual polarity and A beta peptides. This was followed by the lipid fragmentation obtained directly on plaque aggregates at higher laser pulse energies which provided tandem MS information useful for structural elucidation of several lipid species. Majority of the amyloid plaque-associated alterations of lipid species are for the first time reported here. The significance of this technique is that it allows correlating the biological discussion of all detected plaque-associated molecules to the very same individual amyloid plaques which can give novel insights into the molecular pathology of even a single amyloid plaque microenvironment in a specific brain region. Therefore, this allowed us to interpret the possible roles of lipids and amyloid peptides in amyloid plaque-associated pathological events such as focal demyelination, autophagic/lysosomal dysfunction, astrogliosis, inflammation, oxidative stress, and cell death.
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| 10. |
- Osborn, K. E., et al.
(författare)
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Cerebrospinal fluid beta-amyloid(42) and neurofilament light relate to white matter hyperintensities
- 2018
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580. ; 68, s. 18-25
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Tidskriftsartikel (refereegranskat)abstract
- White matter hyperintensities (WMHs) are associated with poorer brain health, but their pathophysiological substrates remain elusive. To better understand the mechanistic underpinnings of WMHs among older adults, this study examined in vivo cerebrospinal fluid biomarkers of beta-amyloid(42) deposition (A beta(42)), hyperphosphorylated tau pathology, neurodegeneration (total tau), and axonal injury (neurofilament light [NFL]) in relation to log-transformed WMHs volume. Participants free of clinical stroke and dementia were drawn from the Vanderbilt Memory & Aging Project (n = 148, 72 +/- 6 years). Linear regression models adjusted for age, sex, race/ethnicity, education, intracranial volume, modified Framingham Stroke Risk Profile (excluding points assigned for age), cognitive diagnosis, and APOE-epsilon 4 carrier status. A beta(42) (beta = -0.001, p = 0.007) and NFL (beta = 0.0003, p = 0.01) concentrations related to WMHs but neither hyperphosphorylated tau nor total tau associations with WMHs reached statistical significance (p-values > 0.21). In a combined model, NFL accounted for 3.2% of unique variance in WMHs and A beta(42) accounted for an additional 4.3% beyond NFL, providing novel evidence of the co-occurrence of at least 2 distinct pathways for WMHs among older adults, including amyloid deposition and axonal injury. (C) 2018 Elsevier Inc. All rights reserved.
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