| 101. |
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| 102. |
- Wallenius, Ville, 1970, et al.
(författare)
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The lipocalins retinol-binding protein-4, lipocalin-2 and lipocalin-type prostaglandin D2-synthase correlate with markers of inflammatory activity, alcohol intake and blood lipids, but not with insulin sensitivity in metabolically healthy 58-year-old Swedish men
- 2011
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Ingår i: Experimental and clinical endocrinology & diabetes. - : Georg Thieme Verlag KG. - 1439-3646 .- 0947-7349. ; 119:2, s. 75-80
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Tidskriftsartikel (refereegranskat)abstract
- The lipocalins retinol-binding protein (RBP)-4, lipocalin-2 and lipocalin-type prostaglandin D-synthase (L-PGDS) have been suggested to mediate obesity-associated insulin resistance and other metabolic co-morbidities. The role of lipocalins is however controversial and it is unclear whether they have a physiological role in regulation of insulin sensitivity and metabolic function in clinically healthy humans. Therefore, we examined the correlations between serum levels of RBP-4, L-PGDS and lipocalin-2 and insulin sensitivity and other metabolic parameters in non-diabetic subjects selected to display variations in insulin sensitivity. 100 clinically healthy 58-year-old Swedish men were selected by stratified sampling among 818 screened subjects to represent quintiles of varying degrees of insulin sensitivity. Insulin sensitivity was measured by the euglycaemic hyperinsulinaemic clamp method. Serum levels of lipocalins and cytokines were determined using antibody-based techniques. Serum lipids were measured by standardized laboratory methods. None of the measured lipocalins showed any correlations with insulin sensitivity. However, we found that lipocalin-2 and L-PGDS were correlated with each other, but not with RBP-4. Lipocalin-2 and L-PGDS were positively correlated with soluble TNF- receptors 1 and 2 and negatively with alcohol consumption and serum HDL. Further, lipocalin-2 was correlated with interleukin-6 whereas RBP-4 was negatively correlated with TNF-α. □These results suggest that RBP-4, lipocalin-2 and L-PGDS do not regulate insulin sensitivity in healthy men. Rather the expression levels of lipocalin-2 and L-PGDS, but not RBP-4, seemed to reflect inflammatory activity and were inversely correlated with alcohol intake and serum HDL levels.
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| 103. |
- Wallin, Anders, 1950, et al.
(författare)
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Progression from mild to pronounced MCI is not associated with cerebrospinal fluid biomarker deviations.
- 2011
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 32:3, s. 193-7
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aim: Detection of cerebrospinal fluid (CSF) biomarker deviations improve prediction of progression from mild cognitive impairment (MCI) to dementia. However, it is not settled whether the same pattern exists in patients progressing from very mild to more pronounced MCI. Given that neurodegenerative processes occur very early in the disease course, we also expected to find biomarker deviations in these patients. Methods: A total of 246 memory clinic patients with non-progressive (n = 161), progressive (n = 19), or converting (n = 66) MCI, 67 with stable dementia, and 80 controls were followed for 24 months. At baseline, CSF total tau (T-tau), β-amyloid 1–42 (Aβ42) and the light subunit of neurofilament protein (NFL) were determined. Results: Patients with converting MCI and stable dementia had lower CSF Aβ42 concentrations and higher T-tau concentrations and NFL in comparison with controls and non-progressive/progressive MCI (p < 0.0005). No differences were found between progressive and non-progressive MCI. Conclusion: As expected, biomarker deviations predicted progression from MCI to dementia. Contrary to our hypothesis, progression from very mild MCI to more pronounced MCI was not reflected by biomarker deviations. The results suggest that the measured biomarkers are not early disease markers, or alternatively Alzheimer or vascular pathology is not the underlying cause in this patient group.
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| 104. |
- Wallin, Å K, et al.
(författare)
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CSF biomarkers predict a more malignant outcome in Alzheimer disease.
- 2010
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Ingår i: Neurology. - 1526-632X. ; 74:19, s. 1531-7
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate if patterns of CSF biomarkers (T-tau, P-tau, and Abeta42) can predict cognitive progression, outcome of cholinesterase inhibitor (ChEI) treatment, and mortality in Alzheimer disease (AD). METHODS: We included outpatients with AD (n = 151) from a prospective treatment study with ChEI. At baseline, patients underwent cognitive assessments and lumbar puncture. The patients were assessed longitudinally. The 5-year survival rate was evaluated. CSF-Abeta42, T-tau, and P-tau were analyzed at baseline. K-means cluster analysis including the 3 CSF biomarkers was carried out. RESULTS: Cluster 1 contained 87 patients with low levels of Abeta42 and relatively low levels of T-tau and P-tau. Cluster 2 contained 52 patients with low levels of Abeta42 and intermediate levels of T-tau and P-tau. Cluster 3 contained 12 patients with low levels of Abeta42 and very high levels of CSF T-tau and P-tau. There were no differences between the clusters regarding age, gender, years of education, baseline instrumental activities of daily living, or APOE genotype. Even though there was no difference between cluster 3 and the other clusters in disease duration or global rating, the patients in cluster 3 performed worse on cognitive tests already at baseline. Patients in cluster 3 exhibited a very poor outcome of ChEI treatment. Finally, cognition deteriorated faster over time and the mortality rate was substantially increased in cluster 3. CONCLUSION: A subgroup of patients with Alzheimer disease with extreme levels of CSF biomarkers exhibits worse clinical outcomes over time, including faster progression of cognitive deficits, no response to ChEI treatment, and a higher mortality.
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| 105. |
- Zetterberg, Henrik, 1973, et al.
(författare)
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Amyloid beta and APP as biomarkers for Alzheimer's disease.
- 2010
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Ingår i: Experimental gerontology. - : Elsevier BV. - 1873-6815 .- 0531-5565. ; 45:1, s. 23-9
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Forskningsöversikt (refereegranskat)abstract
- Intense research during the past decade has aimed at dissecting the molecular pathogenesis of Alzheimer's disease (AD). Primarily, the focus has been directed towards brain amyloid pathology and its relation to synaptic and neuronal loss. Clearly, AD is associated with accumulation of amyloid beta (Abeta) in the brain. Further, the results of many experimental studies suggest that certain forms of Abeta may act as initiators in the disease process with potent toxic effects at the synaptic level. Molecular aberrations in the AD brain are reflected in the cerebrospinal fluid (CSF). Core CSF biomarkers include secreted Abeta and amyloid precursor protein (APP) isoforms, Abeta oligomers and beta-site APP-cleaving enzyme 1 (BACE1). This article reviews recent research advances on CSF and plasma Abeta-related biomarkers for AD and how they may reflect pathogenic changes in AD-affected neuronal networks. We also consider their usefulness in clinical practice and in clinical trials.
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| 106. |
- Zetterberg, Henrik, 1973, et al.
(författare)
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Biochemical markers in Alzheimer's disease clinical trials.
- 2010
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Ingår i: Biomarkers in medicine. - 1752-0363. ; 4:1, s. 91-8
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Forskningsöversikt (refereegranskat)abstract
- This article summarizes how biochemical markers may aid in the development of novel treatments that interfere with fundamental pathogenic processes in Alzheimer's disease. Details are given on the potential use of biomarkers in Alzheimer's disease clinical trials as additional inclusion criteria to enrich study populations with participants who really suffer from the disease, as a means to stratify study participants into meaningful subgroups that may benefit differently from the treatment, and as tools to detect desired biochemical effects and undesired side effects of the drug.
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| 107. |
- Zetterberg, Henrik, 1973, et al.
(författare)
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Cerebrospinal fluid analysis should be considered in patients with cognitive problems.
- 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
- Hepatologists assay liver enzymes and cardiologists structural heart proteins in serum to diagnose and monitor their patients. This way of thinking has not quite made it into the memory clinics yet, in spite of the availability of validated cerebrospinal fluid biomarkers for key pathological events in the brain in neurodegeneration. Here, we argue that a spinal tap should be considered in all patients who seek medical advice for memory problems and list the highly relevant clinical questions CSF analyses can address.
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| 108. |
- Zetterberg, Henrik, 1973, et al.
(författare)
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Hypoxia Due to Cardiac Arrest Induces a Time-Dependent Increase in Serum Amyloid β Levels in Humans
- 2011
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:12, s. e28263-
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Tidskriftsartikel (refereegranskat)abstract
- Amyloid β (Aβ) peptides are proteolytic products from amyloid precursor protein (APP) and are thought to play a role in Alzheimer disease (AD) pathogenesis. While much is known about molecular mechanisms underlying cerebral Aβ accumulation in familial AD, less is known about the cause(s) of brain amyloidosis in sporadic disease. Animal and postmortem studies suggest that Aβ secretion can be up-regulated in response to hypoxia. We employed a new technology (Single Molecule Arrays, SiMoA) capable of ultrasensitive protein measurements and developed a novel assay to look for changes in serum Aβ42 concentration in 25 resuscitated patients with severe hypoxia due to cardiac arrest. After a lag period of 10 or more hours, very clear serum Aβ42 elevations were observed in all patients. Elevations ranged from approximately 80% to over 70-fold, with most elevations in the range of 3-10-fold (average approximately 7-fold). The magnitude of the increase correlated with clinical outcome. These data provide the first direct evidence in living humans that ischemia acutely increases Aβ levels in blood. The results point to the possibility that hypoxia may play a role in the amyloidogenic process of AD.
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| 109. |
- Zetterberg, Henrik, 1973, et al.
(författare)
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Low Incidence of Post-Lumbar Puncture Headache in 1,089 Consecutive Memory Clinic Patients
- 2010
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Ingår i: European Neurology. - : S. Karger AG. - 1421-9913 .- 0014-3022. ; 63:6, s. 326-330
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To examine the incidence of post-lumbar puncture headache (PLPH) in patients admitted for cognitive disturbances. Methods: The incidence of PLPH and other general (subdural hematoma, meningitis, encephalitis) or local (local pain, spinal hematoma, local infection) complications was evaluated in 1,089 consecutive patients (aged 23-89 years) who underwent lumbar puncture as a part of the routine diagnostic evaluation between February 2001 and March 2007 at a specialized memory clinic. Results: 28 (2.6%) of the patients reported PLPH of mild severity. No other local or general complications occurred. Conclusions: The incidence of PLPH in patients with cognitive disturbances is low and CSF analyses can thus be part of the diagnostic work-up at memory clinics. Copyright (C) 2010 S. Karger AG, Basel
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| 110. |
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