| 1. |
- Brinkmalm-Westman, Ann, 1966, et al.
(författare)
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SNAP-25 is a promising novel cerebrospinal fluid biomarker for synapse degeneration in Alzheimer's disease
- 2014
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Ingår i: Molecular Neurodegeneration. - : Springer Science and Business Media LLC. - 1750-1326. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Synaptic degeneration is an early pathogenic event in Alzheimer's disease, associated with cognitive impairment and disease progression. Cerebrospinal fluid biomarkers reflecting synaptic integrity would be highly valuable tools to monitor synaptic degeneration directly in patients. We previously showed that synaptic proteins such as synaptotagmin and synaptosomal-associated protein 25 (SNAP-25) could be detected in pooled samples of cerebrospinal fluid, however these assays were not sensitive enough for individual samples. Results: We report a new strategy to study synaptic pathology by using affinity purification and mass spectrometry to measure the levels of the presynaptic protein SNAP-25 in cerebrospinal fluid. By applying this novel affinity mass spectrometry strategy on three separate cohorts of patients, the value of SNAP-25 as a cerebrospinal fluid biomarker for synaptic integrity in Alzheimer's disease was assessed for the first time. We found significantly higher levels of cerebrospinal fluid SNAP-25 fragments in Alzheimer's disease, even in the very early stages, in three separate cohorts. Cerebrospinal fluid SNAP-25 differentiated Alzheimer's disease from controls with area under the curve of 0.901 (P < 0.0001). Conclusions: We developed a sensitive method to analyze SNAP-25 levels in individual CSF samples that to our knowledge was not possible previously. Our results support the notion that synaptic biomarkers may be important tools for early diagnosis, assessment of disease progression, and to monitor drug effects in treatment trials.
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| 2. |
- Portelius, Erik, 1977, et al.
(författare)
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An Alzheimer's disease-specific beta-amyloid fragment signature in cerebrospinal fluid.
- 2006
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Ingår i: Neuroscience letters. - : Elsevier BV. - 0304-3940. ; 409:3, s. 215-9
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Tidskriftsartikel (refereegranskat)abstract
- Pathogenic events in Alzheimer's disease (AD) involve an imbalance between the production and clearance of the neurotoxic beta-amyloid peptide (Abeta), especially the 42 amino acid peptide Abeta1-42. While much is known about the production of Abeta1-42, many questions remain about how the peptide is degraded. To investigate the degradation pattern, we developed a method based on immunoprecipitation combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry that determines the Abeta degradation fragment pattern in cerebrospinal fluid (CSF). We found in total 18 C-terminally and 2 N-terminally truncated Abeta peptides and preliminary data indicated that there were differences in the detected Abeta relative abundance pattern between AD and healthy controls. Here, we provide direct evidence that an Abeta fragment signature consisting of Abeta1-16, Abeta1-33, Abeta1-39, and Abeta1-42 in CSF distinguishes sporadic AD patients from non-demented controls with an overall accuracy of 86%.
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| 3. |
- Öhrfelt Olsson, Annika, 1973, et al.
(författare)
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Identification of Novel α-Synuclein Isoforms in Human Brain Tissue by using an Online NanoLC-ESI-FTICR-MS Method.
- 2011
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Ingår i: Neurochemical research. - : Springer Science and Business Media LLC. - 1573-6903 .- 0364-3190. ; 36:11, s. 2029-2042
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Tidskriftsartikel (refereegranskat)abstract
- Parkinson's disease (PD) and Dementia with Lewy bodies (DLB) are neurodegenerative diseases that are characterized by intra-neuronal inclusions of Lewy bodies in distinct brain regions. These inclusions consist mainly of aggregated α-synuclein (α-syn) protein. The present study used immunoprecipitation combined with nanoflow liquid chromatography (LC) coupled to high resolution electrospray ionization Fourier transform ion cyclotron resonance tandem mass spectrometry (ESI-FTICR-MS/MS) to determine known and novel isoforms of α-syn in brain tissue homogenates. N-terminally acetylated full-length α-syn (Ac-α-syn(1-140)) and two N-terminally acetylated C-terminally truncated forms of α-syn (Ac-α-syn(1-139) and Ac-α-syn(1-103)) were found. The different forms of α-syn were further studied by Western blotting in brain tissue homogenates from the temporal cortex Brodmann area 36 (BA36) and the dorsolateral prefrontal cortex BA9 derived from controls, patients with DLB and PD with dementia (PDD). Quantification of α-syn in each brain tissue fraction was performed using a novel enzyme-linked immunosorbent assay (ELISA).
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| 4. |
- Hansson, Sarah, 1976, et al.
(författare)
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Cystatin C in cerebrospinal fluid and multiple sclerosis.
- 2007
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Ingår i: Annals of neurology. - : Wiley. - 0364-5134. ; 62:2, s. 193-196
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: A recent study using surface-enhanced laser desorption/ionization time-of-flight analysis of cerebrospinal fluid identified a 12.5 kDa truncated isoform of cystatin C (CysC) as a specific biomarker for multiple sclerosis (MS). METHODS: Surface-enhanced laser desorption/ionization time-of-flight analysis of cerebrospinal fluid samples from 43 MS patients and 46 healthy control subjects. RESULTS: Full-length CysC (13.4 kDa) concentration was similar in MS and control samples. The 12.5 kDa CysC protein was produced from full-length CysC by N-terminal cleavage during storage at -20 degrees C. INTERPRETATION: The 12.5 kDa CysC isoform is a storage-related artifact and is not useful as a diagnostic marker for MS.
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