| 61. |
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| 62. |
- Duits, Flora H., et al.
(författare)
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The cerebrospinal fluid "Alzheimer profile": Easily said, but what does it mean?
- 2014
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Ingår i: Alzheimer's & Dementia. - : Elsevier. - 1552-5260 .- 1552-5279. ; 10:6, s. 713-723
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Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to identify the most useful definition of the "cerebrospinal fluid Alzheimer profile," based on amyloid-beta(1-42) (A beta(42)), total tau, and phosphorylated tau (p-tau), for diagnosis and prognosis of Alzheimers disease (AD). Methods: We constructed eight Alzheimer profiles with previously published combinations, including regression formulas and simple ratios. We compared their diagnostic accuracy and ability to predict dementia due to AD in 1385 patients from the Amsterdam Dementia Cohort. Results were validated in an independent cohort (n = 1442). Results: Combinations outperformed individual biomarkers. Based on the sensitivity of the best performing regression formulas, cutoffs were chosen at 0.52 for the tau/A beta(42) ratio and 0.08 for the p-tau/A beta(42) ratio. Ratios performed similar to formulas (sensitivity, 91%-93%; specificity, 81%-84%). The same combinations best predicted cognitive decline in mild cognitive impairment patients. Validation confirmed these results, especially regarding the tau/A beta(42) ratio. Conclusions: A tau/A beta(42) ratio of greater than0.52 constitutes a robust cerebrospinal fluid Alzheimer profile. We recommend using this ratio to combine biomarkers.
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| 63. |
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| 64. |
- Edvinsson, Lars, et al.
(författare)
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Neuropeptides in cerebrospinal fluid of patients with Alzheimer's disease and dementia with frontotemporal lobe degeneration
- 1993
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Ingår i: Dementia (Switzerland). - 1013-7424. ; 4:3-4, s. 71-167
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Tidskriftsartikel (refereegranskat)abstract
- The two major primary degenerative dementias, dementia of Alzheimer type (DAT) and frontal lobe degeneration of non-Alzheimer type (FLD) have several clinical features in common but also many symptoms that differ. In a clinical material of 80 patients with either of the two forms of dementia (DAT = 39, FLD = 41) we have studied the levels of neuropeptides in the cerebrospinal fluid (CSF) in order to find biochemical markers for CNS affection. The dementia forms were evaluated by careful clinical analysis, psychometric testing and measurement of regional cerebral blood flow. Approximately one third of the subjects died during the completion of the study and neuropathology was performed, confirming the diagnoses. We observed reductions in the CSF levels of antidiuretic hormone and somatostatin in both DAT and FLD. A strong tendency to reduction was noted for neuropeptide Y (NPY). There was a correlation with the duration of disease demonstrating a significant reduction in NPY levels in subjects with DAT. Most notably there was a strong reduction in the levels of delta sleep inducing peptide (DSIP) in DAT cases only. The levels of DSIP in FLD were the same as in controls. The reverse was found for corticotropin releasing factor (CRF) which had a significant reduction in FLD patients but not in those with DAT. The present study indicates a difference in the CSF levels of neuropeptides, observations that these may serve as biochemical markers which differentiate DAT and FLD.
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| 65. |
- Ewers, Michael, et al.
(författare)
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Body mass index is associated with biological CSF markers of core brain pathology of Alzheimer's disease
- 2012
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 33:8, s. 1599-1608
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Tidskriftsartikel (refereegranskat)abstract
- Weight changes are common in aging and Alzheimer's disease (AD) and postmortem findings suggest a relation between lower body mass index (BMI) and increased AD brain pathology. In the current multicenter study, we tested whether lower BMI is associated with higher core AD brain pathology as assessed by cerebrospinal fluid (CSF)-based biological markers of AD in 751 living subjects: 308 patients with AD, 296 subjects with amnestic mild cognitive impairment (MCI), and 147 elderly healthy controls (HC). Based upon a priori cutoff values on CSF concentration of total tau and beta-amyloid (A beta(1-42)), subjects were binarized into a group with abnormal CSF biomarker signature (CSF+) and those without (CSF-). Results showed that BMI was significantly lower in the CSF+ when compared with the CSF- group (F = 27.7, df = 746, p < 0.001). There was no interaction between CSF signature and diagnosis or apolipoprotein E (ApoE) genotype. In conclusion, lower BMI is indicative of AD pathology as assessed with CSF-based biomarkers in demented and nondemented elderly subjects. Published by Elsevier Inc.
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| 66. |
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| 67. |
- Gao, Carol Man, et al.
(författare)
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Aβ40 oligomers identified as a potential biomarker for the diagnosis of Alzheimer's disease.
- 2010
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 5:12
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's Disease (AD) is the most prevalent form of dementia worldwide, yet the development of therapeutics has been hampered by the absence of suitable biomarkers to diagnose the disease in its early stages prior to the formation of amyloid plaques and the occurrence of irreversible neuronal damage. Since oligomeric Aβ species have been implicated in the pathophysiology of AD, we reasoned that they may correlate with the onset of disease. As such, we have developed a novel misfolded protein assay for the detection of soluble oligomers composed of Aβ x-40 and x-42 peptide (hereafter Aβ40 and Aβ42) from cerebrospinal fluid (CSF). Preliminary validation of this assay with 36 clinical samples demonstrated the presence of aggregated Aβ40 in the CSF of AD patients. Together with measurements of total Aβ42, diagnostic sensitivity and specificity greater than 95% and 90%, respectively, were achieved. Although larger sample populations will be needed to confirm this diagnostic sensitivity, our studies demonstrate a sensitive method of detecting circulating Aβ40 oligomers from AD CSF and suggest that these oligomers could be a powerful new biomarker for the early detection of AD.
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| 68. |
- Gerhardsson, Lars, 1952, et al.
(författare)
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Cerebrospinal fluid/plasma quotients of essential and non-essential metals in patients with Alzheimer's disease.
- 2011
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Ingår i: Journal of neural transmission (Vienna, Austria : 1996). - : Springer Science and Business Media LLC. - 1435-1463 .- 0300-9564. ; 118:6, s. 957-62
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Tidskriftsartikel (refereegranskat)abstract
- In this study, the quotients (Q) between metal concentrations in cerebrospinal fluid (CSF) and plasma were studied in subjects with Alzheimer's disease (AD) and referents to investigate if the leakage through the blood-CSF barrier (BCB) increased with increased duration and severity of the disease. Concentrations of 18 metals (Mg, Ca, Mn, Fe, Co, Ni, Cu, Zn, Se, Rb, Sr, Mo, Cd, Sn, Sb, Cs, Hg, and Pb) were determined by ICP-MS in plasma and cerebrospinal fluid in 264 patients with AD, and in 54 healthy referents. The quotients Q (Mn), Q (Rb), Q (Sb), Q (Pb) and Q (Hg) were significantly lower (p ≤ 0.003) and Q (Co) significantly higher (p ≤ 0.001) in subjects with AD as compared with the controls. Subjects in a subgroup with more severe AD, showed the same pattern. The metal leakage into CSF did not increase with increased duration and/or severity of the disease. The permeability of BCB varied considerably between the studied metals with low median quotients (Q ≤ 0.02) for Cd, Cu, Sb, Se and Zn and higher median quotients for Ca (Q ~ 0.5) and Mg (Q ~ 1.3), probably partly depending on differences in size and lipophilicity of metal-carrier complexes and specific carrier mechanisms.
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| 69. |
- Gerhardsson, Lars, 1952, et al.
(författare)
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Concentrations of metals, beta-amyloid and tau-markers in cerebrospinal fluid in patients with Alzheimer's disease.
- 2009
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 28:1, s. 88-94
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/AIMS: In this study, metal concentrations were related to the levels of well-known Alzheimer markers in cerebrospinal fluid (CSF), such as amyloid-beta (Abeta), total tau (T-tau) and phosphorylated-tau (P-tau). METHODS: Concentrations of 19 metals (Mg, Ca, V, Mn, Fe, Co, Ni, Cu, Zn, Se, Rb, Sr, Mo, Cd, Sn, Sb, Cs, Hg and Pb by inductively coupled plasma-mass spectrometry) and the levels of Abeta, T-tau and P-tau in CSF were determined (xMAP technology) in 264 patients with Alzheimer's disease (AD), and in 54 healthy referents. RESULTS: The AD subjects showed positive correlations between CSF-T-tau and CSF-P-tau versus CSF-Mn (r(s) = 0.22, p = 0.004; r(s) = 0.18, p = 0.021). CSF-T-tau, however, showed a negative correlation with CSF-Cs (r(s) = -0.17; p = 0.027). In subjects with severe AD, CSF-Abeta showed a strong positive correlation with CSF-Cs (r(s) = 0.49; p = 0.026), while CSF-T-tau showed a strong negative correlation with CSF-Cs (r(s) = -0.49; p = 0.026). Also, CSF P-tau was negatively associated with CSF-Cs (r(s) = -0.41; p = 0.06). CONCLUSION: The different relationships between the CSF-levels of Abeta and tau-markers versus the levels of CSF-Mn and CSF-Cs may be due to different binding affinity between these metals and metal binding proteins in the CSF and the surrounding brain.
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| 70. |
- Gerhardsson, Lars, 1952, et al.
(författare)
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Metal concentrations in plasma and cerebrospinal fluid in patients with Alzheimer's disease.
- 2008
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 25:6, s. 508-15
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/AIMS: The homeostasis of essential metals such as copper, iron, selenium and zinc may be altered in the brain of subjects with Alzheimer's disease (AD). METHODS: Concentrations of metals (magnesium, calcium, vanadium, manganese, iron, cobalt, nickel, copper, zinc, selenium, rubidium, strontium, molybdenum, cadmium, tin, antimony, cesium, mercury and lead) were determined in plasma and cerebrospinal fluid (CSF) by inductively coupled plasma mass spectrometry in 173 patients with AD and in 87 patients with the combination of AD and minor vascular components (AD + vasc). Comparison was made with 54 healthy controls. RESULTS: The plasma concentrations of manganese and total mercury were significantly higher in subjects with AD (p < 0.001) and AD + vasc (p
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