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Wide distribution of alpha-synuclein oligomers in Creutzfeldt-Jakob disease detected by a novel proximity ligation assay

R. Valenti-Azcarate, I. Martinez-Valbuena, C. Caballero, I. Marcilla Garcia, G. Marti, M. Carmona-Abellan, M. Tuñon-Alvarez, MR. Luquin-Piudo (Pamplona, Spain)

Meeting: 2019 International Congress

Abstract Number: 753

Keywords: Alpha-synuclein, Prion diseases. See Transmissible spongiform encephalopathies

Session Information

Date: Monday, September 23, 2019

Session Title: Other

Session Time: 1:45pm-3:15pm

Location: Agora 2 West, Level 2

Objective: The objective of this work is to assess if oligomeric forms of alpha-synuclein exist in patients with Creutzfeldt-Jakob disease.

Background: Prion diseases, the most frequent variety of which in human is Creutzfeldt-Jakob disease (CJD), are characterized by post-translational accumulation of the host-encoded prion protein PrP in an amyloid misfolded isoform (PrPsc). In a previous work, our group found that brains of CJD patients present alpha synuclein inclusions. Recently a novel method has been developed to reveal early alpha-synuclein pathology.

Method: We analyze the expression of alpha-synuclein oligomers in fifteen cases of sporadic CJD in order to determine the existence and location of pathological protein seeds. We focused our work on the frontal cortex, putamen, amygdala and cerebellum, since they are specially affected in CJD. Besides the proximity ligation assay, immunofluorescence was performed to locate, characterize and understand the histological localization of these seeds.

Results: Wide distribution of alpha-synuclein oligomers were found in all regions examined.  These inclusions were more prominent in the Dentate nucleus and in the cerebellar granular layer than in the frontal cortex, where profuse cytoplasmic inclusions were observed. Six of the thirteen CJD brains examined presented oligomers of α-synuclein in Purkinje cells.

Conclusion: The existence of both oligomers and Lewy dots in cases of CJD disease could suggest a common neurodegenerative pathway between CJD and Parkinson disease. The relevance of these oligomers for CJD physiopathology will be further discussed.

To cite this abstract in AMA style:

R. Valenti-Azcarate, I. Martinez-Valbuena, C. Caballero, I. Marcilla Garcia, G. Marti, M. Carmona-Abellan, M. Tuñon-Alvarez, MR. Luquin-Piudo. Wide distribution of alpha-synuclein oligomers in Creutzfeldt-Jakob disease detected by a novel proximity ligation assay [abstract]. Mov Disord. 2019; 34 (suppl 2). https://www.mdsabstracts.org/abstract/wide-distribution-of-alpha-synuclein-oligomers-in-creutzfeldt-jakob-disease-detected-by-a-novel-proximity-ligation-assay/. Accessed July 14, 2025.
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