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000263624 037__ $$aDZNE-2023-00843
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000263624 1001_ $$00000-0001-7645-5448$$aZhang, Shuyu$$b0
000263624 245__ $$aAlpha-synuclein fibrils amplified from multiple system atrophy and Parkinson's disease patient brain spread after intracerebral injection into mouse brain.
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000263624 520__ $$aParkinson'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.
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000263624 650_2 $$2MeSH$$aAnimals
000263624 650_2 $$2MeSH$$aMice
000263624 650_2 $$2MeSH$$aalpha-Synuclein: metabolism
000263624 650_2 $$2MeSH$$aParkinson Disease: pathology
000263624 650_2 $$2MeSH$$aMultiple System Atrophy: pathology
000263624 650_2 $$2MeSH$$aBrain: pathology
000263624 650_2 $$2MeSH$$aSynucleinopathies: pathology
000263624 650_2 $$2MeSH$$aAntibodies
000263624 650_7 $$2NLM Chemicals$$aSnca protein, mouse
000263624 650_7 $$2Other$$aParkinson's disease
000263624 650_7 $$2Other$$aalpha-synuclein
000263624 650_7 $$2Other$$amicroglia
000263624 650_7 $$2Other$$amultiple system atrophy
000263624 650_7 $$2Other$$apatient-derived fibrils
000263624 650_7 $$2NLM Chemicals$$aalpha-Synuclein
000263624 650_7 $$2NLM Chemicals$$aAntibodies
000263624 7001_ $$aDauer, Karina$$b1
000263624 7001_ $$0P:(DE-2719)2812850$$aStrohäker, Timo$$b2
000263624 7001_ $$0P:(DE-2719)2812849$$aTatenhorst, Lars$$b3$$udzne
000263624 7001_ $$00000-0003-4959-2169$$aCaldi Gomes, Lucas$$b4
000263624 7001_ $$aMayer, Simon$$b5
000263624 7001_ $$aJung, Byung Chul$$b6
000263624 7001_ $$aKim, Woojin S$$b7
000263624 7001_ $$aLee, Seung-Jae$$b8
000263624 7001_ $$aBecker, Stefan$$b9
000263624 7001_ $$00000-0003-1948-1580$$aLiesche-Starnecker, Friederike$$b10
000263624 7001_ $$0P:(DE-2719)2810591$$aZweckstetter, Markus$$b11
000263624 7001_ $$0P:(DE-2719)2812561$$aLingor, Paul$$b12$$udzne
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