| 1. |
- Abramsson, Alexandra, 1973, et al.
(författare)
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No Association of LOXL1 Gene Polymorphisms with Alzheimer's Disease
- 2011
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Ingår i: NeuroMolecular Medicine. - : Springer Science and Business Media LLC. - 1535-1084 .- 1559-1174. ; 13:2, s. 160-166
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Tidskriftsartikel (refereegranskat)abstract
- Aggregation of amyloid-beta is one of the major characteristics in brains of patients with Alzheimer's disease (AD). Although several mechanisms behind the formation of such aggregates have been suggested the regulatory factors are still unknown. The present study aimed at investigating the association of lysyl oxidase-like 1 (LOXL1) polymorphisms with AD diagnosis and cerebrospinal fluid biomarkers (CSF) for the disease. Proteins of the lysyl oxidase (LOX) family are involved in cross-linking extracellular matrix proteins to insoluble fibers and have been associated with neurodegenerative diseases including AD. Genetic polymorphisms in LOXL1 (rs1048661, rs3825942, and rs2165241) have been linked to exfoliation syndrome and exfoliation glaucoma, conditions that have shown association with AD. The polymorphisms were genotyped by Taqman allelic discrimination in a study sample including AD patients (n = 318) and controls (n = 575). In a subgroup of the population, the polymorphisms were analyzed in relation to APOE epsilon 4 genotype and to CSF (T-tau, P-tau, and A beta(1-42)). No evidence for associations of these polymorphisms with risk for AD or any of the studied CSF biomarkers measured was found. These results do not support LOXL1 as being a major risk gene for AD.
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| 2. |
- 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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| 3. |
- Alves, Guido, et al.
(författare)
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CSF amyloid-β and tau proteins, and cognitive performance, in early and untreated Parkinson's Disease: the Norwegian ParkWest study
- 2010
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Ingår i: Journal of neurology, neurosurgery, and psychiatry. - : BMJ. - 1468-330X .- 0022-3050. ; 81:10, s. 1080-1086
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Tidskriftsartikel (refereegranskat)abstract
- Background Alzheimer's disease (AD) pathology is found in a considerable portion of patients with Parkinson's disease (PD), particularly those with early dementia (PDD). Altered cerebrospinal fluid (CSF) levels of amyloid-beta (Abeta) and tau proteins have been found in PDD, with intermediate changes for Abeta42 in non-demented PD. The authors investigated whether AD-related CSF protein levels are altered and relate to neuropsychological performance in early, untreated PD. Methods CSF concentrations of Abeta42, Abeta40 and Abeta38 were measured by electrochemiluminiscene and levels of total tau (T-tau) and phosphorylated tau (P-tau) by ELISA in 109 newly diagnosed, unmedicated, non-demented, community-based PD patients who had undergone comprehensive neuropsychological testing, and were compared with those of 36 age-matched normal controls and 20 subjects with mild AD. Results PD patients displayed significant reductions in Abeta42 (19%; p=0.009), Abeta40 (15.5%; p=0.008) and Abeta38 (23%; p=0.004) but not T-tau (p=0.816) or P-tau (p=0.531) compared with controls. CSF Abeta42 reductions in PD were less marked than in AD (53%; p=0.002). Sequential regression analyses demonstrated significant associations between CSF levels of Abeta42 (beta=0.205; p=0.019), Abeta40 (beta=0.378; p<0.001) and Abeta38 (beta=0.288; p=0.001) and memory impairment, but not executive-attentional or visuospatial dysfunction. Tau protein levels did not correlate with cognitive measures. Conclusion CSF Abeta levels are altered in a subset of patients with early PD and relate to memory impairment. Our study suggests that alterations in Abeta protein metabolism may contribute to the heterogeneity in pattern and course of cognitive decline associated with PD. Longitudinal studies are needed to clarify the clinical significance of CSF Abeta peptides as prognostic biomarkers in PD.
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| 4. |
- Andersson, Maria A, et al.
(författare)
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The cognitive profile and CSF biomarkers in dementia with Lewy bodies and Parkinson's disease dementia.
- 2011
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Ingår i: International journal of geriatric psychiatry. - : Wiley. - 1099-1166 .- 0885-6230. ; 26:1, s. 100-5
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Tidskriftsartikel (refereegranskat)abstract
- Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) may be viewed as different points on a continuum reflecting the regional burden and distribution of pathology. An important clinical consideration is overlapping Alzheimer's disease (AD) pathology, since it has been reported that associated AD pathology in DLB shortens survival and leads to a more rapid cognitive decline. We aimed to investigate cerebrospinal fluid (CSF) biomarkers and the associated cognitive profile in DLB and PDD.
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| 5. |
- Andreasen, Niels, et al.
(författare)
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Neuroinflammation Screening in Immunotherapy Trials against Alzheimer's Disease.
- 2010
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Ingår i: International journal of Alzheimer's disease. - : Hindawi Limited. - 2090-0252. ; :638379
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Tidskriftsartikel (refereegranskat)abstract
- Due to side effects in the form of meningoencephalitis in the interrupted phase II AN1792 trial of active antiamyloid β(Aβ) immunization against Alzheimer's disease (AD), there has been concern that anti-Aβ immunization may cause destructive neuroinflammation. Here, we report on two patients fulfilling clinical AD criteria who were diagnosed with Lyme neuroborreliosis during screening before inclusion in anti-Aβ immunotherapy trials. The two cases illustrate the necessity of careful biochemical screening for neuroinflammatory/neuroinfectious conditions before an AD diagnosis is made and before clinical AD patients are included in trials of therapy that could impact the immune system. Should the two cases have been included and deteriorated, additional investigations might have led to the erroneous conclusion that therapy-induced meningoencephalitis had occurred.
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| 6. |
- Balldin, Jan, 1935, et al.
(författare)
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Gamma-glutamyltransferase in alcohol use disorders: Modification of decision limits in relation to treatment goals?
- 2010
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Ingår i: Scandinavian journal of clinical and laboratory investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 70:2, s. 71-74
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Serum gamma-glutamyltransferase (GGT) is recommended as a marker for alcohol use disorders by the Swedish National Guidelines for Addiction, although it has a low sensitivity and specificity. GGT is inexpensive and easily accessible but additional knowledge is required on how to use the marker in patients with various levels of alcohol intake. Levels of GGT were obtained from 37 male social drinkers (< 100 grams pure alcohol weekly) and 18 former alcohol-dependent males with long-term (6 +/- 5 years) abstinence. Reproducibility was calculated through repeated blood samplings. Mean serum activity of GGT, in former alcohol-dependent males, was 0.26 microkat/L with an intra-class correlation coefficient of 0.85. In social drinkers, these figures were 0.34 microkat/L and 0.92, respectively. In treatment of males, with the goal of abstinence, upper reference limit is suggested to be 0.40 microkat/L. Goals of non-harmful drinking (< 100 grams weekly) suggest higher limits (0.62 microkat/L). Thirty percent increase of GGT should be suggestive of relapse.
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| 7. |
- Berggren, Ulf, 1948, et al.
(författare)
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Dopamine D2 Receptor Genotype Is Associated with Increased Mortality at a 10-Year Follow-up of Alcohol-Dependent Individuals.
- 2010
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Ingår i: Alcohol and alcoholism. - : Oxford University Press (OUP). - 1464-3502 .- 0735-0414. ; 45:1, s. 1-5
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Because the TAQ1 A1 allele may be associated with alcohol-related medical illnesses, and medical illnesses in alcohol-dependent individuals are associated with increased mortality, we test the hypothesis that the TAQ1 A1 allele of the DRD2 gene is associated with increased mortality in alcohol-dependent individuals. METHODS: Following an index treatment episode, a 10-year follow-up study in 366 alcohol-dependent individuals was performed. The TAQ1 A1/A2 DRD2 genotype and allele frequencies were compared between those deceased and those still living at the 10-year point. In addition, the genotype and allele frequencies of these alcohol-dependent individuals were compared to that in 578 control subjects. RESULTS: The prevalence of the A1 allele differed between the deceased and living patients and the controls: 47% of the deceased were A1+, compared to 37% of the living patients and 32% of the controls. The frequency of the TAQ1 A1/A2 genotype also differed between the groups. Thus, 43% had the A1/A2 genotype in comparison with 32% in the living patients and 29% in the controls. The TAQ 1 A1 allele frequency differed between the groups. The frequency of A1 allele was 25% in the deceased patients compared to 21% in the living patients and 17% in the controls. CONCLUSION: The TAQ I A1 allele of the DRD2 gene (or DRD2 gene region) was associated with increased mortality over a 10-year period in alcohol-dependent individuals.
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| 8. |
- Bjerke, Maria, 1977, et al.
(författare)
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Cerebrospinal Fluid Matrix Metalloproteinases and Tissue Inhibitor of Metalloproteinases in Combination with Subcortical and Cortical Biomarkers in Vascular Dementia and Alzheimer's Disease.
- 2011
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Ingår i: Journal of Alzheimer's disease : JAD. - 1387-2877. ; 27:3, s. 665-676
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD) and vascular dementia (VaD) are intertwined by mixed dementia (MD) harboring varying degrees of AD pathology in combination with cerebrovascular disease. The aim was to assess whether there is a difference in the cerebrospinal fluid (CSF) profile, of selected proteins, between patients with VaD and MD with subcortical vascular disease (SVD), AD, and healthy controls that could contribute in the separation of the groups. The study included 30 controls, 26 SVD patients (9 VaD and 17 MD) and 30 AD patients. The protein panel included total tau (T-tau), hyperphosphorylated tau 181 (P-tau181), amyloid β 1-42 (Aβ1-42), neurofilament light (NF-L), myelin basic protein (MBP), heart fatty acid binding protein (H-FABP), matrix metalloproteinases (MMP-1, -2, -3, -9, and -10), and tissue inhibitors of metalloproteinases (TIMP-1 and -2). Immunochemical methods were utilized for quantification of the proteins in CSF and data analysis was performed with a multivariate discriminant algorithm. The concentrations of MBP, TIMP-1, P-tau181, NF-L, T-tau, MMP-9, Aβ1-42, and MMP-2 contributed the most to the separation between SVD and AD, with a sensitivity of 89% and a specificity of 90% (AUC = 0.92). MBP and NF-L performed the best in discriminating SVD from controls, while T-tau and Aβ1-42 contributed the most in segregating AD from controls. The CSF biomarkers reflecting AD pathology (T-tau, P-tau181, and Aβ1-42), white matter lesions (NF-L and MBP) and matrix remodeling (MMP-9 and TIMP-1) perform well in differentiating between SVD and AD patients.
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| 9. |
- Bjerke, Maria, 1977, et al.
(författare)
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Confounding factors influencing amyloid Beta concentration in cerebrospinal fluid.
- 2010
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Ingår i: International journal of Alzheimer's disease. - : Hindawi Limited. - 2090-0252. ; 2010
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Tidskriftsartikel (refereegranskat)abstract
- Background. Patients afflicted with Alzheimer's disease (AD) exhibit a decrease in the cerebrospinal fluid (CSF) concentration of the 42 amino acid form of beta-amyloid (Abeta(42)). However, a high discrepancy between different centers in measured Abeta(42) levels reduces the utility of this biomarker as a diagnostic tool and in monitoring the effect of disease modifying drugs. Preanalytical and analytical confounding factors were examined with respect to their effect on the measured Abeta(42) level. Methods. Aliquots of CSF samples were either treated differently prior to Abeta(42) measurement or analyzed using different commercially available xMAP or ELISA assays. Results. Confounding factors affecting CSF Abeta(42) levels were storage in different types of test tubes, dilution with detergent-containing buffer, plasma contamination, heat treatment, and the origin of the immunoassays used for quantification. Conclusion. In order to conduct multicenter studies, a standardized protocol to minimize preanalytical and analytical confounding factors is warranted.
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| 10. |
- Blennow, Kaj, 1958, et al.
(författare)
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Cerebrospinal fluid and plasma biomarkers in Alzheimer disease
- 2010
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Ingår i: Nature reviews. Neurology. - : Springer Science and Business Media LLC. - 1759-4766 .- 1759-4758. ; 6:3, s. 131-44
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Forskningsöversikt (refereegranskat)abstract
- Intense multidisciplinary research has provided detailed knowledge of the molecular pathogenesis of Alzheimer disease (AD). This knowledge has been translated into new therapeutic strategies with putative disease-modifying effects. Several of the most promising approaches, such as amyloid-beta immunotherapy and secretase inhibition, are now being tested in clinical trials. Disease-modifying treatments might be at their most effective when initiated very early in the course of AD, before amyloid plaques and neurodegeneration become too widespread. Thus, biomarkers are needed that can detect AD in the predementia phase or, ideally, in presymptomatic individuals. In this Review, we present the rationales behind and the diagnostic performances of the core cerebrospinal fluid (CSF) biomarkers for AD, namely total tau, phosphorylated tau and the 42 amino acid form of amyloid-beta. These biomarkers reflect AD pathology, and are candidate markers for predicting future cognitive decline in healthy individuals and the progression to dementia in patients who are cognitively impaired. We also discuss emerging plasma and CSF biomarkers, and explore new proteomics-based strategies for identifying additional CSF markers. Furthermore, we outline the roles of CSF biomarkers in drug discovery and clinical trials, and provide perspectives on AD biomarker discovery and the validation of such markers for use in the clinic.
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