SCIENTIFIC HUB

Follow the evidence.

SCIENTIFIC LITERATURE · MED

Multiple System Atrophy: Pathology, Pathogenesis, and Path Forward.

Annu Rev Pathol · 2025-01-02

DOI: 10.1146/annurev-pathmechdis-051122-104528PMID: 39405585

Check source for accessResearch Support, Non-U.S. Gov't; Review; Journal Article; Research Support, N.I.H., ExtramuralOriginal source ↗

Research overview

The text below is the source article’s original abstract under a verified reuse license. cc by

Multiple system atrophy (MSA) is a fatal neurodegenerative disease characterized by autonomic failure and motor impairment. The hallmark pathologic finding in MSA is widespread oligodendroglial cytoplasmic inclusions rich in aggregated α-synuclein (αSyn). MSA is widely held to be an oligodendroglial synucleinopathy, and we outline lines of evidence to support this assertion, including the presence of early myelin loss. However, we also consider emerging data that support the possibility of neuronal or immune dysfunction as a primary driver of MSA. These hypotheses are placed in the context of a major recent discovery that αSyn is conformationally distinct in MSA versus other synucleinopathies such as Parkinson's disease. We outline emerging techniques in epidemiology, genetics, and molecular pathology that will shed more light on this mysterious disease. We anticipate a future in which cutting-edge developments in personalized disease modeling, including with pluripotent stem cells, bridge mechanistic developments at the bench and real benefits at the bedside.

Scientific assessment

01

Research question

Assess the question within the original study’s scope.

02

Methods & sample

Check the source article for study design and sample details.

03

Key findings

An editorially approved findings summary is not yet published for this record.

04

Limitations

Generalizability, bias and clinical meaning require separate assessment.

Methods, samples and clinical conclusions are not inferred from bibliographic metadata.