Dataset Information

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

ABSTRACT: Synucleinopathies [Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA)] share filamentous ?-synuclein assemblies in nerve cells and glial cells. We compared the abilities of brain extracts from MSA and PD patients to induce neuronal ?-synuclein assembly and neurodegeneration following intracerebral injection in heterozygous mice transgenic for human mutant A53T ?-synuclein. MSA extracts were more potent than PD extracts in inducing ?-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 ?-synuclein inclusions were invariably Campbell-Switzer-positive and Gallyas-negative, irrespective of whether MSA or PD brain extracts were injected. The ?-synuclein inclusions of non-injected homozygous mice transgenic for A53T ?-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 ?-synuclein.

SUBMITTER: Lavenir I

PROVIDER: S-EPMC6745790 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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

Lavenir Isabelle I Passarella Daniela D Masuda-Suzukake Masami M Curry Annabelle A Holton Janice L JL Ghetti Bernardino B Goedert Michel M

Acta neuropathologica communications 20190916 1

Synucleinopathies [Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA)] share filamentous α-synuclein assemblies in nerve cells and glial cells. We compared the abilities of brain extracts from MSA and PD patients to induce neuronal α-synuclein assembly and neurodegeneration following intracerebral injection in heterozygous mice transgenic for human mutant A53T α-synuclein. MSA extracts were more potent than PD extracts in inducing α-synuclein assembly and ...[more]

PMID: 31522685

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Project description:Synucleinopathies are neurodegenerative diseases that are associated with the misfolding and aggregation of α-synuclein, including Parkinson's disease, dementia with Lewy bodies and multiple system atrophy1. Clinically, it is challenging to differentiate Parkinson's disease and multiple system atrophy, especially at the early stages of disease2. Aggregates of α-synuclein in distinct synucleinopathies have been proposed to represent different conformational strains of α-synuclein that can self-propagate and spread from cell to cell3-6. Protein misfolding cyclic amplification (PMCA) is a technique that has previously been used to detect α-synuclein aggregates in samples of cerebrospinal fluid with high sensitivity and specificity7,8. Here we show that the α-synuclein-PMCA assay can discriminate between samples of cerebrospinal fluid from patients diagnosed with Parkinson's disease and samples from patients with multiple system atrophy, with an overall sensitivity of 95.4%. We used a combination of biochemical, biophysical and biological methods to analyse the product of α-synuclein-PMCA, and found that the characteristics of the α-synuclein aggregates in the cerebrospinal fluid could be used to readily distinguish between Parkinson's disease and multiple system atrophy. We also found that the properties of aggregates that were amplified from the cerebrospinal fluid were similar to those of aggregates that were amplified from the brain. These findings suggest that α-synuclein aggregates that are associated with Parkinson's disease and multiple system atrophy correspond to different conformational strains of α-synuclein, which can be amplified and detected by α-synuclein-PMCA. Our results may help to improve our understanding of the mechanism of α-synuclein misfolding and the structures of the aggregates that are implicated in different synucleinopathies, and may also enable the development of a biochemical assay to discriminate between Parkinson's disease and multiple system atrophy.

Dataset Information

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

Publications

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

Similar Datasets

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