%0 Journal Article
%A Zhang, Shuyu
%A Dauer, Karina
%A Strohäker, Timo
%A Tatenhorst, Lars
%A Caldi Gomes, Lucas
%A Mayer, Simon
%A Jung, Byung Chul
%A Kim, Woojin S
%A Lee, Seung-Jae
%A Becker, Stefan
%A Liesche-Starnecker, Friederike
%A Zweckstetter, Markus
%A Lingor, Paul
%T Alpha-synuclein fibrils amplified from multiple system atrophy and Parkinson's disease patient brain spread after intracerebral injection into mouse brain.
%J Brain pathology
%V 33
%N 5
%@ 1015-6305
%C Oxford
%I Wiley-Blackwell
%M DZNE-2023-00843
%P e13196
%D 2023
%X 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.
%K Animals
%K Mice
%K alpha-Synuclein: metabolism
%K Parkinson Disease: pathology
%K Multiple System Atrophy: pathology
%K Brain: pathology
%K Synucleinopathies: pathology
%K Antibodies
%K Snca protein, mouse (NLM Chemicals)
%K Parkinson's disease (Other)
%K alpha-synuclein (Other)
%K microglia (Other)
%K multiple system atrophy (Other)
%K patient-derived fibrils (Other)
%K alpha-Synuclein (NLM Chemicals)
%K Antibodies (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%2 pmc:PMC10467043
%$ pmid:37485772
%R 10.1111/bpa.13196
%U https://pub.dzne.de/record/263624