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- Mattsson, Niklas, 1979, et al.
(författare)
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Reference measurement procedures for Alzheimer's disease cerebrospinal fluid biomarkers: definitions and approaches with focus on amyloid β42.
- 2012
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Ingår i: Biomarkers in medicine. - : Future Medicine Ltd. - 1752-0371 .- 1752-0363. ; 6:4, s. 409-17
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Tidskriftsartikel (refereegranskat)abstract
- Cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) are increasingly used in clinical settings, research and drug trials. However, their broad-scale use on different technology platforms is hampered by the lack of standardization at the level of sample handling, determination of concentrations of analytes and the absence of well-defined performance criteria for in vitro diagnostic or companion diagnostic assays, which influences the apparent concentration of the analytes measured and the subsequent interpretation of the data. There is a need for harmonization of CSF AD biomarker assays that can reliably, across centers, quantitate CSF biomarkers with high analytical precision, selectivity and stability over long time periods. In this position paper, we discuss reference procedures for the measurement of CSF AD biomarkers, especially amyloid β42 and tau. We describe possible technical approaches, focusing on a selected reaction monitoring mass spectrometry assay as a candidate reference method for quantification of CSF amyloid β42.
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| 2. |
- Jonsson, Michael, 1955, et al.
(författare)
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Low Cerebrospinal Fluid Sulfatide Predicts Progression of White Matter Lesions - The LADIS Study
- 2012
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 34:1, s. 61-67
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: Demyelination and axonal degeneration are the hallmarks of established white matter lesions (WML). The neurochemistry of ongoing WML is only partially known. We explored cerebrospinal fluid (CSF) substances as markers of brain tissue damage in relation to progression of WML rated on magnetic resonance imaging. Methods: CSF from elderly individuals with WML was analyzed for amyloid markers, total tau, hyperphosphorylated t, neurofilament protein light subunit, sulfatide and CSF/serum-albumin ratio. After 3 years, a follow-up magnetic resonance imaging was performed. Progression of WML was rated using the Rotterdam Progression Scale (RPS). Results: 37 subjects (age 73.6 +/- 4.6 years) were included. Subjects with more pronounced progression (RPS > 2; n = 15) had lower mean sulfatide concentration at baseline as compared to subjects with no or minimal progression (RPS 0-2; n = 22) according to univariate analyses (p = 0.009). Sulfatide was the only biomarker that predicted the RPS score according to regression analysis, explaining 18.9% of the total variance (r = 0.38, p = 0.015). Conclusion: The correlation of CSF sulfatide levels and RPS scores may reflect a remyelination response to the demyelination process associated with WML. Furthermore, the results strengthen the notion that WML pathology is different from that of Alzheimer's disease.
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| 3. |
- Wallin, Anders, 1950, et al.
(författare)
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Characteristic clinical presentation and CSF biomarker pattern in cerebral small vessel disease
- 2012
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Ingår i: Journal of the Neurological Sciences. - : Elsevier BV. - 0022-510X. ; 322:1-2, s. 192-196
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Tidskriftsartikel (refereegranskat)abstract
- To be able to live a good, independent life cognitive functions need to be intact. Dementia, stroke and neuropsychiatric disorders are the major disorders underlying disability. Stroke is usually a consequence of an underlying vessel wall disease that has lasted for a longer period. This vessel wall disease is commonly silent or without prominent symptoms. Damage to the small penetrating arterioles of the brain, arteriolosclerosis, induced by aging and hypertension, as well as other factors such as diabetes and genetic vulnerability, plays an important role in the origin of white matter changes. The pathological vascular wall process leads to lumen constriction, impaired ability to change lumen diameter according to metabolic needs and possible ischemic-hypoxic tissue damage in the vulnerable vascular architectural terminal areas of the long penetrating arteries. The arteriolosclerotic blood vessels are associated with inflammation and remodelling of the extracellular matrix. Enzymes connected to this process have also been found to be involved in demyelination and blood brain barrier opening but also in the repair process of angiogenesis and neurogenesis. Biochemical changes reflecting these processes might be early indicators of small vessel disease and hence increase the knowledge about the disease characteristic mechanisms. Moreover, monitoring disease modifying treatment effects can be an important application for small vessel disease specific biochemical markers. (c) 2012 Elsevier B.V. All rights reserved.
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