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PLoS One. 2018 Aug 29;13(8):e0202954. doi: 10.1371/journal.pone.0202954. eCollection 2018.

Extending the functional characteristics of naturally occurring autoantibodies against β-Amyloid, Prion Protein and α-Synuclein.

Author information

Chair of Geriatrics, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
Department of Neurology, Philipps-University, Marburg, Germany.
Department of Neurology, RWTH Aachen, Aachen, Germany.
Department of Hematology and Immunology, Justus-Liebig-University, Giessen, Germany.
Department of Neurology, University Goettingen, Goettingen, Germany.



Abnormal aggregation of proteins induces neuronal cell loss in neurodegenerative disorders such as Alzheimer's Disease, Creutzfeldt-Jakob Disease and Parkinson's Disease. Specific stimuli initialize conformational changes in physiological proteins, causing intra- or extracellular protein aggregation. We and other groups have identified naturally occurring autoantibodies (nAbs) as part of the human antibody pool that are able to prevent peptide fibrillation. These nAbs show a rescue effect following exposure of toxic aggregates on neurons, and they support microglial uptake of aggregated peptides.


Identification of a putative common epitope among the relevant proteins β-Amyloid, α-Synuclein and Prion Protein for the respective nAbs.


Binding affinity between the aforementioned proteins and nAbs was tested by Dot Blot, ELISA and SPR-technology. Furthermore, the functionality of the protein-nAbs-complexes was studied in Thioflavin-T assays and microglial uptake experiments to study dependent inhibition of protein aggregation and enhancement of Fcγ mediated uptake by microglial cells.


β-Amyloid and Prion Protein fragment showed considerable binding affinity and functional efficacy for all applied nAbs. Thereby, no significant difference within the different nAbs was detected. In contrast, α-Synuclein was bound exclusively by nAbs-α-Synuclein, which was reproduced in all binding studies. Surprisingly, functional assays with α-Synuclein revealed no significant effect of nAbs in comparison to IVIg treatment. However, all applied nAbs as well as IVIg show a minimal functionality on the microglial uptake of α-Synuclein.


nAbs-Aβ, nAbs-PrP possibly display comparable affinity to the same structural epitope within Aβ and PrP106-126 A117V whereas the epitope recognized by nAbs-α-Syn is only present in α-Syn. The structural similarity of Aβ and PrP fragment promotes the outline for an efficient antibody for the treatment of several neurodegenerative disorders and extend the functional characteristics of the investigated nAbs.

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Conflict of interest statement

The authors have the following interests. The DEMPARK study was partly funded by an unrestricted grant from Novartis. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

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