| 1. |
- Johansson, Per, et al.
(författare)
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Cerebrospinal Fluid Biomarkers for Alzheimer's Disease: Diagnostic Performance in a Homogeneous Mono-Center Population
- 2011
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 24:3, s. 537-546
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Tidskriftsartikel (refereegranskat)abstract
- The cerebrospinal fluid (CSF) biomarkers amyloid-beta (A beta)(1-42), T-tau, and P-tau have good diagnostic accuracy for clinically diagnosed Alzheimer's disease (AD). However, in multi-center studies, the predictive values of the CSF biomarkers have been lower, possibly due to differences in procedures for lumbar puncture and CSF handling and storage, and to differences in patient populations, clinical evaluations, and diagnostic procedures. Here we investigate the diagnostic accuracy of CSF biomarkers in a well defined homogeneous mono-center population. We also evaluate an extended panel of amyloid related biomarkers. Sixty consecutive patients admitted for cognitive impairment to a memory clinic were recruited. The participants included patients with AD or mild cognitive impairment (MCI) diagnosed with AD upon follow-up (n = 32), patients with stable MCI (n = 13), patients with other dementias diagnosed at primary evaluation or upon follow-up (n = 15), and healthy controls (n = 20). CSF was analyzed for A beta(1-42), T-tau, P-tau, A beta(X-38), A beta(X-40), A beta(X-42), sA beta PP alpha, and sA beta PP beta. In multivariate analysis, the core biomarkers A beta(1-42), T-tau, and P-tau demonstrated a high ability to diagnose AD versus the combined groups of controls and stable MCI, with an area under the receiver operating characteristic curve (AUROC) of 0.97 (95% CI 0.93-1.00, p < 0.0001). The additional biomarkers only marginally increased AUROC to 0.98 (95% CI 0.95-1.00, p < 0.0001), this increase mainly mediated by A beta(X-42). In conclusion, CSF biomarkers A beta(1-42), T-tau, and P-tau have very high diagnostic accuracy in a well defined cohort of untreated patients, demonstrating the excellent potency of CSF biomarkers to identify pathological processes in AD when a stringent analytical protocol is used.
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| 2. |
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| 3. |
- Johansson, Per, 1966, et al.
(författare)
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Mild dementia is associated with increased adrenal secretion of cortisol and precursor sex steroids in women.
- 2011
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Ingår i: Clinical endocrinology. - : Wiley. - 1365-2265 .- 0300-0664. ; 75:3, s. 301-308
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Tidskriftsartikel (refereegranskat)abstract
- Context Sex steroid levels decrease with increasing age, but little is known whether this is of importance for the age-related decline in cognitive function. Design and patients A cross-sectional study of 50 (26 men) consecutive patients under primary evaluation of cognitive impairment (D group) and 18 (9 men) matched healthy controls (C group). Measurements Sex steroid and precursor levels were determined in serum and, when measurable, in cerebrospinal fluid (CSF) using gas chromatography/mass spectroscopy (GC-MS) or liquid chromatography/mass spectroscopy (LC-MS). Sex hormone binding globulin (SHBG) and cortisol concentrations were measured using conventional assays. Results Patients in the D group had higher 24-h urine cortisol levels and increased serum levels of dehydroepiandrosterone (DHEA) and its sulphate ester dihydroepiandrosterone sulphate (DHEAS), androsterone (ADT), and oestrone (E1) and its sulphate ester E1S, compared with the controls. When men and women were analysed separately, increased serum concentrations of E1 and E1S were observed in both D men and D women, whereas increased levels of other sex steroids and cortisol were seen only in D women. Conclusions In both D men and women, serum E1 and E1S levels were increased, whereas other changes were gender specific and only seen in D women. Further studies are needed to determine whether these changes are a cause of, or merely a consequence of, cognitive impairment in elderly subjects.
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| 4. |
- Johansson, Per, et al.
(författare)
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Reduced cerebrospinal fluid level of thyroxine in patients with Alzheimer's disease
- 2013
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 1873-3360 .- 0306-4530. ; 38:7, s. 1058-1066
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Tidskriftsartikel (refereegranskat)abstract
- Background: Little is known of the association between thyroid hormones in the central nervous system and Alzheimer's disease (AD). We determined thyroid hormone levels in serum and cerebrospinal fluid (CSF) in a well-defined homogeneous mono-center population. Methods: Fifty-nine consecutive patients under primary evaluation for cognitive impairment were recruited. The participants included patients with AD or mild cognitive impairment (MCI) diagnosed with AD upon follow-up (n = 31), patients with stable MCI (SMCI, n = 13), patients with other dementias (n = 15), and healthy controls (n = 19). Thyroid hormones in serum and CSF and AD biomarkers in CSF were analyzed using established immunochemical assays. Cognitive impairment was estimated using mini-mental state examination (MMSE). Results: Serum levels of free and total thyroxine (T4) and triiodothyronine (T3) were similar in all groups whereas a marginal increase in serum thyroid-stimulating hormone (TSH) level was observed in the AD patients. The CSF level of total T4 was decreased in patients with AD and other dementias compared to SMCI (both P = 0.01) and healthy controls (both P = 0.001), whereas CSF levels of TSH and total T3 were unchanged. In the total study population, CSF total 14 level correlated positively with MMSE score (r = 0.26, P < 0.05) and negatively with CSF total-tau (T-Tau) level (r = -0.23, P < 0.05). Conclusion: Patients with AD as well as other dementias had signs of mild brain hypothyroidism, which could only to a small extent be detected in serum values. (C) 2012 Elsevier Ltd. All rights reserved.
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| 6. |
- Mattsson, Niklas, 1979, et al.
(författare)
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Cerebrospinal Fluid Microglial Markers in Alzheimer's Disease: Elevated Chitotriosidase Activity but Lack of Diagnostic Utility
- 2011
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Ingår i: NeuroMolecular Medicine. - : Springer Science and Business Media LLC. - 1535-1084 .- 1559-1174. ; 13:2, s. 151-159
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Tidskriftsartikel (refereegranskat)abstract
- Activated microglial cells, which are the resident macrophages of the central nervous system, surround amyloid beta-plaques in Alzheimer's disease (AD) brains. Inflammation including microglial activation may contribute in AD pathogenesis, and biomarkers for this process may thus be of value to study AD pathogenesis and might facilitate development of therapies targeting these cells. We therefore examined cerebrospinal fluid (CSF) biomarkers in patients with AD, other dementias, mild cognitive impairment and in healthy controls. Samples were analyzed for markers with known association to macrophage activity, including chitotriosidase, YKL-40 (CHI3L1, HC gp-39) and chemokine CC motif ligand 2 (CCL2, MCP1). Patients with AD had higher chitotriosidase activity than controls and patients with stable mild cognitive impairment, consistent with the presence of activated microglial cells in AD brains, but with large overlaps between groups. CCL2 and YKL-40 concentrations did not differ among groups. Microglial markers are unlikely to be useful for AD diagnosis, but might be useful for identification of distinct subgroups of patients, and for the development and implementation of drugs targeting microglial pathology.
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| 7. |
- Mattsson, Niklas, 1979, et al.
(författare)
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Converging Pathways of Chromogranin and Amyloid Metabolism in the Brain
- 2010
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 20:4, s. 1039-1048
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Tidskriftsartikel (refereegranskat)abstract
- Much is unknown regarding the regulation of Alzheimer-related amyloid-beta protein precursor (A beta PP)-processing in the human central nervous system. It has been hypothesized that amyloidogenic A beta PP-processing preferentially occurs in the regulated secretory pathway of neurons. To test this hypothesis we looked for correlations of A beta PP-derived molecules in cerebrospinal fluid (CSF) with chromogranin (Cg) derived peptides, representing the regulated secretion. Patients with Alzheimer's disease (AD, N = 32), multiple sclerosis (MS, N = 50), and healthy controls (N = 70) were enrolled. CSF was analyzed for the amyloid peptides A beta(1-42), A beta(x-42), A beta(x-40), A beta(x-38), alpha-cleaved soluble A beta PP (sA beta PP alpha), beta-cleaved soluble A beta PP (sA beta PP beta), and peptides derived from CgB and SgII (Secretogranin-II, CgC). We investigated CSF levels of the protease BACE1, which processes A beta PP into A beta, in relation to Cg-levels. Finally, we measured Cg levels in cell media from untreated and BACE1-inhibited SH-SY5Y human neuroblastoma cells. CSF Cg levels correlated to sA beta PP and A beta peptides in AD, MS, and controls, and to CSF BACE1. Cell medium from BACE1-inhibited cells had decreased CgB levels. These results suggest that a large part of A beta PP in the human central nervous system is processed in the regulated secretory pathway of neurons.
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| 8. |
- Movérare-Skrtic, Sofia, et al.
(författare)
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Leukocyte Telomere Length (LTL) is reduced in stable mild cognitive impairment but low LTL is not associated with conversion to Alzheimer's Disease: A pilot study
- 2012
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Ingår i: Experimental Gerontology. - : Elsevier BV. - 1873-6815 .- 0531-5565. ; 47:2, s. 179-182
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Tidskriftsartikel (refereegranskat)abstract
- Leukocyte telomere length (LTL) is associated with the aging process and may be related to cognitive aging. Previous studies have shown conflicting results whether LTL is affected in patients with Alzheimer's disease (AD). In this pilot study, we investigated LTL in a well-defined homogeneous mono-center population. Sixty consecutive patients admitted for cognitive impairment to a memory clinic were recruited. The participants included patients with AD or mild cognitive impairment (MCI) diagnosed with AD upon follow-up (n=32), patients with stable MCI (n=13), patients with other dementias diagnosed at primary evaluation or upon follow-up (n=15), and healthy controls (n=20). LTL was determined using a quantitative PCR assay. Patients with AD had similar LTL as healthy controls. Patients with stable MCI had reduced LTL both compared to AD patients (p=0.02) and controls (p=0.008). Subanalyses within the AD group showed that patients with MCI that later converted to AD had similar LTL as patients with clinical diagnosis of AD at primary evaluation and healthy controls whereas the LTL was longer compared to the stable MCI group (p=0.02). There were no correlations between LTL and the core AD biomarkers A beta(1-42), T-tau and P-tau. In conclusion, in this pilot study, patients with AD or MCI that later converted to AD had similar LTL as healthy controls. Patients with stable MCI that did not progress to dementia had reduced LTL compared to controls, which might suggest a more marked biological aging as a cause of the cognitive symptoms in this group. (C) 2011 Elsevier Inc. All rights reserved.
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| 9. |
- Rosén, Christoffer, 1986, et al.
(författare)
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Discriminatory analysis of biochip-derived protein patterns in CSF and plasma in neurodegenerative diseases
- 2011
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Ingår i: Frontiers in Aging Neuroscience. - : Frontiers Media SA. - 1663-4365. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- The role of biomarkers in neurodegenerative diseases has been emphasized by recent research. Future clinical demands for identifying diseases at an early stage may render them essential. The aim of this pilot study was to test the analytical performance of two multiplex assays of cerebral markers on a well-defined clinical material consisting of patients with various neurodegenerative diseases. We measured 10 analytes in plasma and cerebrospinal fluid (CSF) from 60 patients suffering from Alzheimer's disease (AD), vascular dementia, frontotemporal dementia, dementia with Lewy bodies, or mild cognitive impairment, as well as 20 cognitively healthy controls. We used the Randox biochip-based Evidence Investigator™ system to measure the analytes. We found it possible to measure most analytes in both plasma and CSF, and there were some interesting differences between the diagnostic groups, although with large overlaps. CSF heart-type fatty acid-binding protein was increased in AD. Glial fibrillary acidic protein and neutrophil gelatinase-associated lipocalin in CSF and D-dimer in plasma were elevated in patients with cerebrovascular disease. A multivariate statistical analysis revealed that the pattern of analytes could help to differentiate the conditions, although more studies are required to verify this.
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