Silver staining (Campbell-Switzer) of neuronal [alpha]-synuclein assemblies induced by multiple system atrophy and Parkinson's disease brain extracts in transgenic mice

• Published in: Acta neuropathologica communications Vol. 7; no. 1
• Main Authors: Lavenir, Isabelle, Passarella, Daniela, Masuda-Suzukake, Masami, Curry, Annabelle, Holton, Janice L, Ghetti, Bernardino, Goedert, Michel
• Format: Journal Article
• Language: English
• Published: BioMed Central Ltd 16.09.2019
• Subjects: Comparative analysis; Dementia; Gene expression; Genetic engineering; Multiple system atrophy; Neurons
• ISSN: 2051-5960; 2051-5960
• DOI: 10.1186/s40478-019-0804-5

Synucleinopathies [Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA)] share filamentous [alpha]-synuclein assemblies in nerve cells and glial cells. We compared the abilities of brain extracts from MSA and PD patients to induce neuronal [alpha]-synuclein assembly and neurodegeneration following intracerebral injection in heterozygous mice transgenic for human mutant A53T [alpha]-synuclein. MSA extracts were more potent than PD extracts in inducing [alpha]-synuclein assembly and in causing neurodegeneration. MSA assemblies were Campbell-Switzer- and Gallyas-silver-positive, whereas PD assemblies were only Campbell-Switzer-positive, in confirmation of previous findings. However, induced [alpha]-synuclein inclusions were invariably Campbell-Switzer-positive and Gallyas-negative, irrespective of whether MSA or PD brain extracts were injected. The [alpha]-synuclein inclusions of non-injected homozygous mice transgenic for A53T [alpha]-synuclein were also Campbell-Switzer-positive and Gallyas-negative. These findings demonstrate that transgene expression and its intracellular environment dominated over the silver staining properties of the conformers of assembled [alpha]-synuclein. Keywords: [alpha]-Synuclein, Multiple system atrophy, Parkinson's disease, Seeding, Silver staining, Transgenic