Alpha‐synuclein fibrils amplified from multiple system atrophy and Parkinson's disease patient brain spread after intracerebral injection into mouse brain

Author:

Zhang Shuyu1ORCID,Dauer Karina23,Strohäker Timo4,Tatenhorst Lars23,Caldi Gomes Lucas123ORCID,Mayer Simon1,Jung Byung Chul5,Kim Woojin S.67,Lee Seung‐Jae5,Becker Stefan8,Liesche‐Starnecker Friederike910ORCID,Zweckstetter Markus48ORCID,Lingor Paul123ORCID

Affiliation:

1. Clinical Department of Neurology, School of Medicine, University Hospital rechts der Isar Technical University of Munich Munich Germany

2. Department of Neurology University Medical Center Göttingen Göttingen Germany

3. Center for Biostructural Imaging of Neurodegeneration University Medical Center Göttingen Göttingen Germany

4. German Center for Neurodegenerative Diseases (DZNE) Göttingen Germany

5. Department of Biomedical Sciences, Neuroscience Research Institute, Convergence Research Center for Dementia, College of Medicine Seoul National University Seoul South Korea

6. Faculty of Medicine and Health, Brain and Mind Centre and School of Medical Sciences The University of Sydney Sydney New South Wales Australia

7. School of Medical Sciences University of New South Wales and Neuroscience Research Australia Randwick New South Wales Australia

8. Department of NMR Based Structural Biology Max Planck Institute for Multidisciplinary Sciences Göttingen Germany

9. Department of Neuropathology, Institute of Pathology, School of Medicine Technical University Munich Munich Germany

10. Department of Pathology and Molecular Diagnostics, Medical Faculty University of Augsburg Augsburg Germany

Abstract

AbstractParkinson's disease (PD), multiple system atrophy (MSA), and dementia with Lewy bodies (DLB) are neurodegenerative disorders with alpha‐synuclein (α‐syn) aggregation pathology. Different strains of α‐syn with unique properties are suggested to cause distinct clinical and pathological manifestations resulting in PD, MSA, or DLB. To study individual α‐syn spreading patterns, we injected α‐syn fibrils amplified from brain homogenates of two MSA patients and two PD patients into the brains of C57BI6/J mice. Antibody staining against pS129‐α‐syn showed that α‐syn fibrils amplified from the brain homogenates of the four different patients caused different levels of α‐syn spreading. The strongest α‐syn pathology was triggered by α‐syn fibrils of one of the two MSA patients, followed by comparable pS129‐α‐syn induction by the second MSA and one PD patient material. Histological analysis using an antibody against Iba1 further showed that the formation of pS129‐α‐syn is associated with increased microglia activation. In contrast, no differences in dopaminergic neuron numbers or co‐localization of α‐syn in oligodendrocytes were observed between the different groups. Our data support the spreading of α‐syn pathology in MSA, while at the same time pointing to spreading heterogeneity between different patients potentially driven by individual patient immanent factors.

Funder

Deutsche Forschungsgemeinschaft

European Research Council

Michael J. Fox Foundation for Parkinson's Research

Publisher

Wiley

Subject

Neurology (clinical),Pathology and Forensic Medicine,General Neuroscience

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