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| Fältnamn | Indikatorer | Metadata |
|---|---|---|
| 000 | 04284naa a2200433 4500 | |
| 001 | oai:DiVA.org:uu-133826 | |
| 003 | SwePub | |
| 008 | 101116s2010 | |||||||||||000 ||eng| | |
| 024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-1338262 URI |
| 024 | 7 | a https://doi.org/10.1186/1471-2202-11-1242 DOI |
| 040 | a (SwePub)uu | |
| 041 | a engb eng | |
| 042 | 9 SwePub | |
| 072 | 7 | a ref2 swepub-contenttype |
| 072 | 7 | a art2 swepub-publicationtype |
| 100 | 1 | a Kamali-Moghaddam, Masoodu Uppsala universitet,Molekylära verktyg4 aut |
| 245 | 1 0 | a Sensitive detection of A beta protofibrils by proximity ligation :b relevance for Alzheimer's disease |
| 264 | c 2010-10-05 | |
| 264 | 1 | b Springer Science and Business Media LLC,c 2010 |
| 338 | a print2 rdacarrier | |
| 520 | a Background: Protein aggregation plays important roles in several neurodegenerative disorders. For instance, insoluble aggregates of phosphorylated tau and of A beta peptides are cornerstones in the pathology of Alzheimer's disease. Soluble protein aggregates are therefore potential diagnostic and prognostic biomarkers for their cognate disorders. Detection of the aggregated species requires sensitive tools that efficiently discriminate them from monomers of the same proteins. Here we have established a proximity ligation assay (PLA) for specific and sensitive detection of A beta protofibrils via simultaneous recognition of three identical determinants present in the aggregates. PLA is a versatile technology in which the requirement for multiple target recognitions is combined with the ability to translate signals from detected target molecules to amplifiable DNA strands, providing very high specificity and sensitivity. Results: For specific detection of A beta protofibrils we have used a monoclonal antibody, mAb158, selective for A beta protofibrils in a modified PLA, where the same monoclonal antibody was used for the three classes of affinity reagents required in the assay. These reagents were used for detection of soluble Ab aggregates in solid- phase reactions, allowing detection of just 0.1 pg/ml A beta protofibrils, and with a dynamic range greater than six orders of magnitude. Compared to a sandwich ELISA setup of the same antibody the PLA increases the sensitivity of the Ab protofibril detection by up to 25- fold. The assay was used to measure soluble Ab aggregates in brain homogenates from mice transgenic for a human allele predisposing to A beta aggregation. Conclusions: The proximity ligation assay is a versatile analytical technology for proteins, which can provide highly sensitive and specific detection of A beta aggregates - and by implication other protein aggregates of relevance in Alzheimer's disease and other neurodegenerative disorders. | |
| 653 | a MEDICINE | |
| 653 | a MEDICIN | |
| 700 | 1 | a Ekholm Pettersson, Fridau Uppsala universitet,Geriatrik,Molekylär geriatrik4 aut0 (Swepub:uu)fpe17837 |
| 700 | 1 | a Wu, Diu Uppsala universitet,Molekylära verktyg4 aut |
| 700 | 1 | a Englund, Hilleviu Uppsala universitet,Geriatrik,Molekylär geriatrik4 aut0 (Swepub:uu)hieng020 |
| 700 | 1 | a Darmanis, Spyrosu Uppsala universitet,Molekylära verktyg4 aut |
| 700 | 1 | a Lord, Annau Uppsala universitet,Geriatrik,Molekylär geriatrik4 aut0 (Swepub:uu)anlor424 |
| 700 | 1 | a Tavoosidana, Gholamrezau Uppsala universitet,Molekylära verktyg4 aut |
| 700 | 1 | a Sehlin, Dagu Uppsala universitet,Geriatrik,Molekylär geriatrik4 aut0 (Swepub:uu)daseh499 |
| 700 | 1 | a Gustafsdottir, Sigrunu Uppsala universitet,Molekylära verktyg4 aut |
| 700 | 1 | a Nilsson, Lars N. G.u Uppsala universitet,Geriatrik,Molekylär geriatrik4 aut0 (Swepub:uu)lanil255 |
| 700 | 1 | a Lannfelt, Larsu Uppsala universitet,Geriatrik,Molekylär geriatrik4 aut0 (Swepub:uu)lalan021 |
| 700 | 1 | a Landegren, Ulfu Uppsala universitet,Molekylära verktyg4 aut0 (Swepub:uu)ulfland |
| 710 | 2 | a Uppsala universitetb Molekylära verktyg4 org |
| 773 | 0 | t BMC Neuroscienced : Springer Science and Business Media LLCg 11, s. 124-q 11<124-x 1471-2202 |
| 856 | 4 | u https://bmcneurosci.biomedcentral.com/track/pdf/10.1186/1471-2202-11-124 |
| 856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-133826 |
| 856 | 4 8 | u https://doi.org/10.1186/1471-2202-11-124 |
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