| 11. |
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| 12. |
- Olsson, Bob, et al.
(author)
-
Extreme Stability of Chitotriosidase in Cerebrospinal Fluid makes it a Suitable Marker for Microglial Activation in Clinical Trials
- 2012
-
In: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 32:2, s. 273-276
-
Journal article (peer-reviewed)abstract
- Microglia is thought to be important in Alzheimer's disease. Therefore, our aim was to investigate the usefulness of the microglial marker chitotriosidase in clinical trials. Chitotriosidase was analyzed in cerebrospinal fluid from Alzheimer's disease patients on acetylcholine esterase inhibitors (AChEI) and in cerebrospinal fluid from multiple sclerosis patients before and after natalizumab treatment. Chitotriosidase activity was extremely stable during treatment with the non-inflammatory drug AChEI. However, the immunomodulatory treatment with natalizumab led to lower chitotriosidase activity. Thus, chitotriosidase may be useful in clinical trials where microglia is targeted or as a safety biomarker in other trials where the brain is a bystander organ.
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| 13. |
- Olsson, Bob, 1969, et al.
(author)
-
Biomarker-based dissection of neurodegenerative diseases.
- 2011
-
In: Progress in neurobiology. - : Elsevier BV. - 1873-5118 .- 0301-0082. ; 95:4, s. 520-534
-
Research review (peer-reviewed)abstract
- The diagnosis of neurodegenerative diseases within neurology and psychiatry are hampered by the difficulty in getting biopsies and thereby validating the diagnosis by pathological findings. Biomarkers for other types of disease have been readily adopted into the clinical practice where for instance troponins are standard tests when myocardial infarction is suspected. However, the use of biomarkers for neurodegeneration has not been fully incorporated into the clinical routine. With the development of cerebrospinal fluid (CSF) biomarkers that reflect pathological events within the central nervous system (CNS), important clinical diagnostic tools are becoming available. This review summarizes the most promising biomarker candidates that may be used to monitor different types of neurodegeneration and protein inclusions, as well as different types of metabolic changes, in living patients in relation to the clinical phenotype and disease progression over time. Our aim is to provide the reader with an updated lexicon on currently available biomarker candidates, how far they have come in development and how well they reflect pathogenic processes in different neurodegenerative diseases. Biomarkers for specific pathogenetic processes would also be valuable tools both to study disease pathogenesis directly in patients and to identify and monitor the effect of novel treatment strategies.
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| 14. |
- Olsson, Bob, 1969, et al.
(author)
-
Imatinib treatment and Aβ42 in humans.
- 2014
-
In: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 10:5, supplement
-
Journal article (peer-reviewed)abstract
- The first-line treatment in chronic myeloid leukemia (CML), imatinib, has been shown to decrease the production of amyloid-β (Aβ) invitro and in animal studies. However, whether imatinib has this effect in humans is not known.
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| 15. |
- Olsson, Bob, 1969, et al.
(author)
-
The glial marker YKL-40 is decreased in synucleinopathies.
- 2013
-
In: Movement disorders : official journal of the Movement Disorder Society. - : Wiley. - 1531-8257. ; 28:14, s. 1882-1885
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Journal article (peer-reviewed)abstract
- Microglia are resident immunosurveillant cells in the central nervous system, and astrocytes are important for blood flow, plasticity, and neurotransmitter regulation. The aim of this study was to investigate whether astrocyte and microglial activation, estimated through markers in cerebrospinal fluid and serum, differed between synucleinopathies, tauopathies, and controls.
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| 16. |
- Olsson, Bob, 1969, et al.
(author)
-
Apolipoprotein C-I genotype and serum levels of triglycerides, C-reactive protein and coronary heart disease
- 2010
-
In: Metabolism. - : Elsevier BV. - 0026-0495. ; 59:12, s. 1736-1741
-
Journal article (peer-reviewed)abstract
- Apolipoprotein C-I (apoCI) is implicated in lipid metabolism and inflammatory response, both important risk factors for human heart disease. However, most findings come from in vitro or animal studies, whereas data on human apoCI are sparse. To elucidate the role of apoCI in human disease, we analyzed a functional polymorphism in the promoter region of the apoCI gene in relation to blood lipids, C-reactive protein (CRP), coronary artery disease (CAD), and myocardial infarction (MI). Rs11568822 is a 4-base pair insertion/deletion (Ins/Del) polymorphism, and the Ins allele leads to a higher transcription in vitro compared with the Del allele. This polymorphism was analyzed in the Intergene study, a case-control study for CAD (N = 1236), and the Stockholm Heart Epidemiology Program, a case-control study for MI (N = 2774). Subjects homozygous for the Ins genotype had significantly higher serum levels of triglycerides (P = .01 and P = .006) and lower serum levels of CRP (P = .02 and P < .0001) compared with all other subjects in both studies. Similar results were obtained when analyzing only the controls of both studies (P = .002 and P = .0002, triglycerides; P = .002 and P < .0001, CRP). However, apoCI was not associated with CAD or MI. In conclusion, our data show that apoCI genotype is associated with serum levels of triglycerides and CRP, confirming the role of apoCI in lipid metabolism and suggesting that it also influences inflammation.
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| 17. |
- Olsson, Bob, 1969, et al.
(author)
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Cerebrospinal Fluid Levels of Heart Fatty Acid Binding Protein are Elevated Prodromally in Alzheimer's Disease and Vascular Dementia
- 2013
-
In: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 34:3, s. 673-679
-
Journal article (peer-reviewed)abstract
- Heart fatty acid binding protein (HFABP) is expressed in the brain and is elevated in cerebrospinal fluid (CSF) from patients with several forms of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease with dementia, Lewy body dementia, vascular dementia (VaD), and Creutzfeldt-Jakob disease. However, whether HFABP in CSF is a stable biomarker or if it can help predict conversion from mild cognitive impairment (MCI) to AD or VaD has not been well studied. To address the role of HFABP in neurodegeneration, we analyzed CSF levels of HFABP in 96 AD patients and 65 controls and also in 170 patients with MCI with an average follow up time of 5.7 years. For the stability analysis, two CSF samples were collected from 52 AD patients with a six month interval in between. HFABP levels in CSF were very stable over the six month period (r = 0.93, p < 0.001). Furthermore, the CSF levels of HFABP were significantly elevated in AD compared with controls after adjustments for age and gender (p < 0.001). They were also elevated in the patients with MCI that subsequently converted to AD or VaD compared with those that remained stable (p < 0.001 and p < 0.05, respectively). However, ROC curve analysis showed that HFABP had lesser predictive value in determining conversion from MCI to AD and VaD than A beta(42), t-tau, and p-tau. In conclusion, HFABP seems to be a stable CSF biomarker that reflects neuronal cell death in several neurodegenerative disorders, including early stages of AD and VaD.
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| 18. |
- Olsson, Bob, 1969, et al.
(author)
-
Extreme Stability of Chitotriosidase in Cerebrospinal Fluid makes it a Suitable Marker for Microglial Activation in Clinical Trials
- 2012
-
In: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 32:2, s. 273-276
-
Journal article (peer-reviewed)abstract
- Microglia is thought to be important in Alzheimer's disease. Therefore, our aim was to investigate the usefulness of the microglial marker chitotriosidase in clinical trials. Chitotriosidase was analyzed in cerebrospinal fluid from Alzheimer's disease patients on acetylcholine esterase inhibitors (AChEI) and in cerebrospinal fluid from multiple sclerosis patients before and after natalizumab treatment. Chitotriosidase activity was extremely stable during treatment with the non-inflammatory drug AChEI. However, the immunomodulatory treatment with natalizumab led to lower chitotriosidase activity. Thus, chitotriosidase may be useful in clinical trials where microglia is targeted or as a safety biomarker in other trials where the brain is a bystander organ.
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| 19. |
- Olsson, Bob, 1969, et al.
(author)
-
Increased number of B-cells in the red pulp of the spleen in ITP
- 2012
-
In: Annals of Hematology. - : Springer Science and Business Media LLC. - 1432-0584 .- 0939-5555. ; 91:2, s. 271-277
-
Journal article (peer-reviewed)abstract
- Platelets are targeted by autoantibodies and destroyed in the reticuloendothelial system in the spleen, liver and bone marrow in patients with immune thrombocytopenia (ITP). Other mechanisms such as destruction by cytotoxic T-cells and defective production of platelets in the bone marrow also exist. Splenectomy normalizes the platelet count in 70% of ITP patients, however, precious little is known about the spleen in this disease. Our aim was therefore to investigate the splenic morphology and especially the number and localization of splenic leukocytes in patients with ITP and controls and to evaluate factors predicting outcome of splenectomy. Spleen sections from 29 ITP patients and 11 individuals splenectomized due to trauma were analyzed by immunohistochemistry. All except one of the ITP patients had a normalized platelet count 12months after splenectomy and the platelet count was inversely correlated with age. ITP patients had an increased number of B-cells in the red pulp. The number of white pulp B-cells and number of T-cells in both compartments was unchanged. In conclusion, B-cells are increased in the red pulp of the spleen and together with cytotoxic T-cells, helper T-cells and macrophages line the sinusoids enabling the immunological attack on platelets in ITP.
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| 20. |
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