TY  - JOUR
AU  - Zhang, Shuyu
AU  - Dauer, Karina
AU  - Strohäker, Timo
AU  - Tatenhorst, Lars
AU  - Caldi Gomes, Lucas
AU  - Mayer, Simon
AU  - Jung, Byung Chul
AU  - Kim, Woojin S
AU  - Lee, Seung-Jae
AU  - Becker, Stefan
AU  - Liesche-Starnecker, Friederike
AU  - Zweckstetter, Markus
AU  - Lingor, Paul
TI  - Alpha-synuclein fibrils amplified from multiple system atrophy and Parkinson's disease patient brain spread after intracerebral injection into mouse brain.
JO  - Brain pathology
VL  - 33
IS  - 5
SN  - 1015-6305
CY  - Oxford
PB  - Wiley-Blackwell
M1  - DZNE-2023-00843
SP  - e13196
PY  - 2023
AB  - 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.
KW  - Animals
KW  - Mice
KW  - alpha-Synuclein: metabolism
KW  - Parkinson Disease: pathology
KW  - Multiple System Atrophy: pathology
KW  - Brain: pathology
KW  - Synucleinopathies: pathology
KW  - Antibodies
KW  - Snca protein, mouse (NLM Chemicals)
KW  - Parkinson's disease (Other)
KW  - alpha-synuclein (Other)
KW  - microglia (Other)
KW  - multiple system atrophy (Other)
KW  - patient-derived fibrils (Other)
KW  - alpha-Synuclein (NLM Chemicals)
KW  - Antibodies (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C2  - pmc:PMC10467043
C6  - pmid:37485772
DO  - DOI:10.1111/bpa.13196
UR  - https://pub.dzne.de/record/263624
ER  -