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@ARTICLE{Zhang:263624,
author = {Zhang, Shuyu and Dauer, Karina and Strohäker, Timo and
Tatenhorst, Lars and Caldi Gomes, Lucas and Mayer, Simon and
Jung, Byung Chul and Kim, Woojin S and Lee, Seung-Jae and
Becker, Stefan and Liesche-Starnecker, Friederike and
Zweckstetter, Markus and Lingor, Paul},
title = {{A}lpha-synuclein fibrils amplified from multiple system
atrophy and {P}arkinson's disease patient brain spread after
intracerebral injection into mouse brain.},
journal = {Brain pathology},
volume = {33},
number = {5},
issn = {1015-6305},
address = {Oxford},
publisher = {Wiley-Blackwell},
reportid = {DZNE-2023-00843},
pages = {e13196},
year = {2023},
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.},
keywords = {Animals / Mice / alpha-Synuclein: metabolism / Parkinson
Disease: pathology / Multiple System Atrophy: pathology /
Brain: pathology / Synucleinopathies: pathology / Antibodies
/ Snca protein, mouse (NLM Chemicals) / Parkinson's disease
(Other) / alpha-synuclein (Other) / microglia (Other) /
multiple system atrophy (Other) / patient-derived fibrils
(Other) / alpha-Synuclein (NLM Chemicals) / Antibodies (NLM
Chemicals)},
cin = {AG Zweckstetter},
ddc = {610},
cid = {I:(DE-2719)1410001},
pnm = {352 - Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pmc = {pmc:PMC10467043},
pubmed = {pmid:37485772},
doi = {10.1111/bpa.13196},
url = {https://pub.dzne.de/record/263624},
}