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A proximity ligatio...
A proximity ligation assay recognizing phosphorylated α-syn reveals previously undetected α-syn pathology in the brains of synucleinopathy patients and mouse model.
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- Behere, Anish (author)
- Uppsala universitet,Geriatrik,Molecular Geriatrics
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- Ingelsson, Martin (author)
- Uppsala universitet,Geriatrik
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- Ekmark-Lewén, Sara (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Geriatrik
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- Bergström, Joakim (author)
- Uppsala universitet,Geriatrik
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(creator_code:org_t)
- English.
- Related links:
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https://urn.kb.se/re...
Abstract
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- Aim: To enhance detection sensitivity of phosphorylated α-synuclein (pSynS129) on post mortem synucleinopathy brains using the newly developed PLA and characterize possible ‘strain’-specific differences in the synucleinopathy brains.Experimental plan: Four different antibodies detecting different epitopes from N- to C- terminal of α-syn were paired systematically with an antibody detecting pSynS129 to reveal patho-morphological features of α-syn aggregates on post mortem brain tissue. In addition, we tested the application of our novel PLA technique in the A30P-tg mouse model that shows different types of pSynS129 aggregates in different stages of PD.Results: The PLA experiments revealed a wide distribution of pSynS129 aggregates in post mortem synucleinopathy-patient brains. We observed unique staining patterns on the brain tissue sections using only certain antibody combinations in a PLA setup, which could not be visualized using regular immunohistochemistry. In A30P-tg mice, the morphological pattern of PLA signal indicated an age-progressive, intracellular shift of pSynS129 aggregation species from periphery towards soma in the prefrontal cortex.Significance: Here we demonstrate that employing PLA with certain α-syn antibodies pair combinations can enhance detection sensitivity and specificity of α-syn pathology in the respective synucleinopathies. Additionally, it could be a useful tool to monitor the ‘strain’-specific aggregation and intracellular morphology of α-syn on post mortem brain tissue.
Publication and Content Type
- vet (subject category)
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