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- Brinkmalm, Gunnar, et al.
(författare)
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An online nano-LC-ESI-FTICR-MS method for comprehensive characterization of endogenous fragments from amyloid β and amyloid precursor protein in human and cat cerebrospinal fluid.
- 2012
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Ingår i: Journal of mass spectrometry : JMS. - : Wiley. - 1096-9888 .- 1076-5174. ; 47:5, s. 591-603
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Tidskriftsartikel (refereegranskat)abstract
- Amyloid precursor protein (APP) is the precursor protein to amyloid β (Aβ), the main constituent of senile plaques in Alzheimer's disease (AD). Endogenous Aβ peptides reflect the APP processing, and greater knowledge of different APP degradation pathways is important to understand the mechanism underlying AD pathology. When one analyzes longer Aβ peptides by low-energy collision-induced dissociation tandem mass spectrometry (MS/MS), mainly long b-fragments are observed, limiting the possibility to determine variations such as amino acid variants or post-translational modifications (PTMs) within the N-terminal half of the peptide. However, by using electron capture dissociation (ECD), we obtained a more comprehensive sequence coverage for several APP/Aβ peptide species, thus enabling a deeper characterization of possible variants and PTMs. Abnormal APP/Aβ processing has also been described in the lysosomal storage disease Niemann-Pick type C and the major large animal used for studying this disease is cat. By ECD MS/MS, a substitution of Asp7 → Glu in cat Aβ was identified. Further, sialylated core 1 like O-glycans at Tyr10, recently discovered in human Aβ (a previously unknown glycosylation type), were identified also in cat cerebrospinal fluid (CSF). It is therefore likely that this unusual type of glycosylation is common for (at least) species belonging to the magnorder Boreoeutheria. We here describe a detailed characterization of endogenous APP/Aβ peptide species in CSF by using an online top-down MS-based method.
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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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