| 51. |
- Zetterberg, Madeleine, 1969, et al.
(författare)
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Association of complement factor HY402H gene polymorphism with Alzheimer's disease
- 2008
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Ingår i: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. - : Wiley. - 1552-4841. ; 147B:6, s. 720-6
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD) and age-related macular degeneration (AMD) share several epidemiological and biochemical features. The present study aimed to assess the possible influence of the AMD-associated complement factor H (CFH) Y402H (1277T > C) polymorphism on the risk of AD. Caucasian subjects (n=800) meeting the criteria for probable (n = 717) or definite (n = 83) AD and Caucasian non-demented controls (n 1265) were included in this multi-center case-control study, in which genotype and allele frequencies of the CFH 1277T > C polymorphism were determined and related to diagnosis, APOE genotype, Mini-Mental State Examination score (MMSE) and the cerebrospinal fluid (CSF) biomarkers total-tau (T-tau), phospho-tau(181), (P-tau(181)), and beta-amyloid(1-42) (A beta(1-42)). The AMD-associated CFH genotypes (1277CC and 1277TC) were overrepresented in subjects with AD as compared to control individuals (P = 0.029). Positive C carrier status was associated with an odds ratio (OR) for AD of 1.24 (95% confidence interval [CI] 1.02-1.50). When APOE 4 carrier status was included in the regression model, this association was even stronger (OR 1.34, 95% CI: 1.08-1.65, P=0.007). Subgroup analysis showed that the association between CFH C allele positivity and AD was only evident for individuals carrying the APOE epsilon 4 allele. Positive C carrier status was also associated with lower levels of CSF A beta(1-42) selectively in the control group in an APOE epsilon 4-independent manner (P=0.003). In conclusion, the CFH 1277T > C polymorphism seems to influence the risk of AD and there appears to be an interaction between CFH 1277C and APOE epsilon 4 alleles. The CFH 1277C allele may predispose patients for co-morbidity in AD and AMD. (c) 2007 Wiley-Liss, Inc.
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| 52. |
- Zetterberg, Madeleine, 1969, et al.
(författare)
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Methylenetetrahydrofolate reductase genetic polymorphisms in patients with cataract.
- 2005
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Ingår i: American journal of ophthalmology. - : Elsevier BV. - 0002-9394. ; 140:5, s. 932-4
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Hyperhomocysteinemia is commonly associated with polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene. The level of homocysteine can be lowered by dietary intake of folate. A protective effect of folate supplementation has been reported against cataract. Here we investigate MTHFR polymorphisms in human cataract. DESIGN: Retrospective case-control association study. METHODS: Patients with nuclear (n = 77), cortical (n = 155), posterior subcapsular (n = 119), and mixed (n = 151) cataract, and 187 controls were analyzed for the MTHFR 677C-->T and 1298A-->C polymorphisms using minisequencing technique. RESULTS: The wild-type MTHFR 677CC/1298AA genotype was strongly overrepresented among cataract cases (P = .003). This effect was most pronounced in the mixed cataract group (P < .001). Hyperhomocysteinemia-associated genotypes had similar frequencies in cataract and control groups. CONCLUSIONS: The previously reported protective effect of folate against cataract is not due to overrepresentation of hyperhomocysteinemia-associated MTHFR genotypes. Instead, the strong predominance of wild-type MTHFR in cataract may suggest impaired DNA synthesis as a cataractogenic factor.
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| 53. |
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| 54. |
- Zetterberg, Madeleine, 1969, et al.
(författare)
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Ubiquitin carboxy-terminal hydrolase L1 (UCHL1) S18Y polymorphism in Alzheimer's disease.
- 2010
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Ingår i: Molecular neurodegeneration. - : Springer Science and Business Media LLC. - 1750-1326. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: Alzheimer's disease (AD) is characterized by protein aggregates, i.e. senile plaques and neurofibrillary tangles. The ubiquitin-proteasome system has been proposed a role in proteolytic removal of these protein aggregates. Ubiquitin carboxy-terminal hydrolase L1 (UCHL1) is a de-ubiquitinating enzyme with important functions in recycling of ubiquitin. The S18Y polymorphism of the UCHL1 gene confers protection against Parkinson's disease. In this study, the genotype and allele frequencies of the UCHL1 S18Y polymorphism were investigated in 452 AD patients and 234 control subjects, recruited from four memory clinics in Sweden. Using a binary logistic regression model including UCHL1 allele A and APOE epsilon4 allele positivity, age and sex as covariates with AD diagnosis as dependent variable, an adjusted OR of 0.82 ([95% CI 0.55-1.24], P = 0.35) was obtained for a positive UCHL1 allele A carrier status. The present study thus do not support a protective effect of the UCHL1 S18Y polymorphism against AD.
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| 55. |
- Aasa, Jenny, et al.
(författare)
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The genotoxic potency of glycidol established from micronucleus frequency and hemoglobin adduct levels in mice
- 2017
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Ingår i: Food and Chemical Toxicology. - : Elsevier BV. - 0278-6915 .- 1873-6351. ; 100, s. 168-174
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Tidskriftsartikel (refereegranskat)abstract
- Glycidol is a genotoxic animal carcinogen that has raised concern due to its presence in food, as glycidyl fatty acid esters. Here we investigated the genotoxicity of glycidol in BalbC mice (0-120 mg/kg) by monitoring the induction of micronuclei in peripheral blood as a marker of chromosomal damage. The scoring of the micronuclei was assessed by flow cytometry. In the treated mice, the internal dose of glycidol, expressed as area under the concentration-time curve, AUC (mol x L-1 x h; Mh), was measured by dihydroxypropyl adducts to hemoglobin (Hb). The study showed that glycidol induced linear dose dependent increases of Hb adducts (20 pmol/g Hb per mg/kg) and of micronuclei frequencies (12 parts per thousand per mMh). Compared to calculations based on administered dose, an improved dose-response relationship was observed when considering internal dose, achieved through the applied combination of sensitive techniques used for the scoring of micronuclei and AUC estimation of glycidol in the same mice. By comparing with earlier studies on micronuclei induction in mice exposed to ionizing radiation we estimated the radiation dose equivalent (rad-eq.) of glycidol to be ca 15 rad-eq./mMh.
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| 56. |
- Abb, Marcel J.S., et al.
(författare)
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Thermal Stability of Single-Crystalline IrO2(110) Layers : Spectroscopic and Adsorption Studies
- 2020
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Ingår i: Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 124:28, s. 15324-15336
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Tidskriftsartikel (refereegranskat)abstract
- The interaction of ultrathin single-crystalline IrO2(110) films with the gas phase proceeds via the coordinatively unsaturated sites (cus), in particular Ircus, the undercoordinated oxygen species on-top O (Oot) that are coordinated to Ircus, and bridging O (Obr). With the combination of different experimental techniques, such as thermal desorption spectroscopy, scanning tunneling microscopy (STM), high-resolution core-level spectroscopy (HRCLS), infrared spectroscopy, and first-principles studies employing density functional theory calculations, we are able to elucidate surface properties of single-crystalline IrO2(110). We provide spectroscopic fingerprints of the active surface sites of IrO2(110). The freshly prepared IrO2(110) surface is virtually inactive toward gas-phase molecules. The IrO2(110) surface needs to be activated by annealing to 500-600 K under ultrahigh vacuum (UHV) conditions. In the activation step, Ircus sites are liberated from on-top oxygen (Oot) and monoatomic Ir metal islands are formed on the surface, leading to the formation of a bifunctional model catalyst. Vacant Ircus sites of IrO2(110) allow for strong interaction and accommodation of molecules from the gas phase. For instance, CO can adsorb atop on Ircus and water forms a strongly bound water layer on the activated IrO2(110) surface. Single-crystalline IrO2(110) is thermally not very stable although chemically stable. Chemical reduction of IrO2(110) by extensive CO exposure at 473 K is not observed, which is in contrast to the prototypical RuO2(110) system.
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| 57. |
- Abdelhak, Ahmed, et al.
(författare)
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Prognostic performance of blood neurofilament light chain protein in hospitalized COVID-19 patients without major central nervous system manifestations: an individual participant data meta-analysis.
- 2023
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Ingår i: Journal of neurology. - : Springer. - 1432-1459 .- 0340-5354. ; 270:7, s. 3315-3328
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the prognostic value of blood neurofilament light chain protein (NfL) levels in the acute phase of coronavirus disease 2019 (COVID-19).We conducted an individual participant data (IPD) meta-analysis after screening on MEDLINE and Scopus to May 23rd 2022. We included studies with hospitalized adult COVID-19 patients without major COVID-19-associated central nervous system (CNS) manifestations and with a measurement of blood NfL in the acute phase as well as data regarding at least one clinical outcome including intensive care unit (ICU) admission, need of mechanical ventilation (MV) and death. We derived the age-adjusted measures NfL Z scores and conducted mixed-effects modelling to test associations between NfL Z scores and other variables, encompassing clinical outcomes. Summary receiver operating characteristic curves (SROCs) were used to calculate the area under the curve (AUC) for blood NfL.We identified 382 records, of which 7 studies were included with a total of 669 hospitalized COVID-19 cases (mean age 66.2 ± 15.0 years, 68.1% males). Median NfL Z score at admission was elevated compared to the age-corrected reference population (2.37, IQR: 1.13-3.06, referring to 99th percentile in healthy controls). NfL Z scores were significantly associated with disease duration and severity. Higher NfL Z scores were associated with a higher likelihood of ICU admission, need of MV, and death. SROCs revealed AUCs of 0.74, 0.80 and 0.71 for mortality, need of MV and ICU admission, respectively.Blood NfL levels were elevated in the acute phase of COVID-19 patients without major CNS manifestations and associated with clinical severity and poor outcome. The marker might ameliorate the performance of prognostic multivariable algorithms in COVID-19.
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| 58. |
- Abdelnour, C., et al.
(författare)
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Alzheimer's disease cerebrospinal fluid biomarkers predict cognitive decline in lewy body dementia
- 2016
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 31:8, s. 1203-1208
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionAlzheimer's disease pathologies are common in dementia with Lewy bodies, but their clinical relevance is not clear. CSF biomarkers amyloid beta 1-42, total tau, and tau phosphorylated at threonine 181 reflect Alzheimer's disease neuropathology antemortem. In PD, low CSF amyloid beta 1-42 predict long-term cognitive decline, but little is known about these biomarkers as predictors for cognitive decline in Lewy body dementia. The aim of this study was to assess whether Alzheimer's disease CSF biomarkers predict cognitive decline in Lewy body dementia. MethodsFrom a large European dementia with Lewy bodies multicenter study, we analyzed baseline Alzheimer's disease CSF biomarkers and serial MMSE (baseline and 1- and 2-year follow-up) in 100 patients with Lewy body dementia. Linear mixed-effects analyses, adjusted for sex, age, baseline MMSE, and education, were performed to model the association between CSF biomarkers and rate of cognitive decline measured with MMSE. An Alzheimer's disease CSF profile was defined as pathological amyloid beta 1-42 plus pathological total tau or phosphorylated tau. ResultsThe Alzheimer's disease CSF profile, and pathological levels of amyloid beta 1-42, were associated with a more rapid decline in MMSE (2.2 [P < 0.05] and 2.9 points difference [P < 0.01], respectively). Higher total tau values showed a trend toward association without statistical significance (2.0 points difference; P = 0.064), whereas phosphorylated tau was not associated with decline. ConclusionsReduced levels of CSF amyloid beta 1-42 were associated with more rapid cognitive decline in Lewy body dementia patients. Future prospective studies should include larger samples, centralized CSF analyses, longer follow-up, and biomarker-pathology correlation. (c) 2016 International Parkinson and Movement Disorder Society
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| 59. |
- Abramsson, Alexandra, 1973, et al.
(författare)
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Proteomics Profiling of Single Organs from Individual Adult Zebrafish.
- 2010
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Ingår i: Zebrafish. - : Mary Ann Liebert Inc. - 1557-8542 .- 1545-8547. ; 7:2, s. 161-168
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Tidskriftsartikel (refereegranskat)abstract
- Abstract The model organism zebrafish (Danio rerio) is extensively utilized in studies of developmental biology but is also being investigated in the context of a growing list of human age-related diseases. To facilitate such studies, we here present protein expression patterns of adult zebrafish organs, including blood, brain, fin, heart, intestine, liver, and skeletal muscle. Protein extracts were prepared from the different organs of two zebrafish and analyzed using liquid chromatography coupled to high-resolution tandem mass spectrometry. Zebrafish tissue was digested directly after minimal fractionation and cleaned up (the shotgun approach). Proteins were identified using Mascot software. In total, 1394 proteins were identified of which 644 were nonredundant. Of these, 373 demonstrated an organ-specific expression pattern and 57 had not been shown on protein level before. These data emphasize the need for increased research at the protein level to facilitate the selection of candidate proteins for targeted quantification and to refine systematic genetic network analysis in vertebrate development, biology, and disease.
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| 60. |
- Abramsson, Alexandra, 1973, et al.
(författare)
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The zebrafish amyloid precursor protein-b is required for motor neuron guidance and synapse formation.
- 2013
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Ingår i: Developmental biology. - : Elsevier BV. - 1095-564X .- 0012-1606. ; 381:2, s. 377-88
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Tidskriftsartikel (refereegranskat)abstract
- The amyloid precursor protein (APP) is a transmembrane protein mostly recognized for its association with Alzheimer's disease. The physiological function of APP is still not completely understood much because of the redundancy between genes in the APP family. In this study we have used zebrafish to study the physiological function of the zebrafish APP homologue, appb, during development. We show that appb is expressed in post-mitotic neurons in the spinal cord. Knockdown of appb by 50-60% results in a behavioral phenotype with increased spontaneous coiling and prolonged touch-induced activity. The spinal cord motor neurons in these embryos show defective formation and axonal outgrowth patterning. Reduction in Appb also results in patterning defects and changed density of pre- and post-synapses in the neuromuscular junctions. Together, our data show that development of functional locomotion in zebrafish depends on a critical role of Appb in the patterning of motor neurons and neuromuscular junctions.
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