Abstract
Parkinson's disease (PD), multiple system atrophy (MSA), and dementia with Lewy bodies (DLB) are neurodegenerative disorders with alpha-synuclein (& alpha;-syn) aggregation pathology. Different strains of & alpha;-syn with unique properties are suggested to cause distinct clinical and pathological manifestations resulting in PD, MSA, or DLB. To study individual & alpha;-syn spreading patterns, we injected & alpha;-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-& alpha;-syn showed that & alpha;-syn fibrils amplified from the brain homogenates of the four different patients caused different levels of & alpha;-syn spreading. The strongest & alpha;-syn pathology was triggered by & alpha;-syn fibrils of one of the two MSA patients, followed by comparable pS129-& alpha;-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-& alpha;-syn is associated with increased microglia activation. In contrast, no differences in dopaminergic neuron numbers or co-localization of & alpha;-syn in oligodendrocytes were observed between the different groups. Our data support the spreading of & alpha;-syn pathology in MSA, while at the same time pointing to spreading heterogeneity between different patients potentially driven by individual patient immanent factors.
| Item Type: | Journal article |
|---|---|
| Faculties: | Medicine > Munich Cluster for Systems Neurology (SyNergy) |
| Subjects: | 600 Technology > 610 Medicine and health |
| URN: | urn:nbn:de:bvb:19-epub-117332-8 |
| Language: | English |
| Item ID: | 117332 |
| Date Deposited: | 07. Jun 2024, 15:45 |
| Last Modified: | 11. Jun 2024, 14:06 |
| DFG: | Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198 |
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