Journal Article

DZNE-2023-00843

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Alpha-synuclein fibrils amplified from multiple system atrophy and Parkinson's disease patient brain spread after intracerebral injection into mouse brain.

Zhang, S. ; Dauer, K. ; Strohäker, T.DZNE* ; Tatenhorst, L.Extern* ; Caldi Gomes, L. ; Mayer, S. ; Jung, B. C. ; Kim, W. S. ; Lee, S.-J. ; Becker, S. ; Liesche-Starnecker, F. ; Zweckstetter, M.DZNE* ; Lingor, P.Extern*

2023
Wiley-Blackwell Oxford

This record in other databases:    

Please use a persistent id in citations: doi:10.1111/bpa.13196

Abstract: Parkinson'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.

Keyword(s): Animals (MeSH) ; Mice (MeSH) ; alpha-Synuclein: metabolism (MeSH) ; Parkinson Disease: pathology (MeSH) ; Multiple System Atrophy: pathology (MeSH) ; Brain: pathology (MeSH) ; Synucleinopathies: pathology (MeSH) ; Antibodies (MeSH) ; Snca protein, mouse ; Parkinson's disease ; alpha-synuclein ; microglia ; multiple system atrophy ; patient-derived fibrils ; alpha-Synuclein ; Antibodies

---

Contributing Institute(s):

1. Translational Structural Biology (AG Zweckstetter)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2023

---

Database coverage:
; ; ; ; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DOAJ Seal ; Ebsco Academic Search ; IF >= 5 ; JCR ; PubMed Central ; SCOPUS ; Web of Science Core Collection

---