Toward a Biological Definition of Neuronal and Glial Synucleinopathies

Authors

Claudio Soto
Brit Mollenhauer
Oskar Hansson
Un Jung Kang
Roy N Alcalay
David Standaert
Claudia Trenkwalder
Kenneth Marek
Douglas Galasko
Kathleen Poston

Language

English

Publication Date

2-1-2025

Journal

Nature Medicine

DOI

10.1038/s41591-024-03469-7

PMID

39885358

PMCID

PMC12466200

PubMedCentral® Posted Date

9-27-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

Cerebral accumulation of alpha-synuclein (αSyn) aggregates is the hallmark event in a group of neurodegenerative diseases-collectively called synucleinopathies-which include Parkinson's disease, dementia with Lewy bodies and multiple system atrophy. Currently, these are diagnosed by their clinical symptoms and definitively confirmed postmortem by the presence of αSyn deposits in the brain. Here, we summarize the drawbacks of the current clinical definition of synucleinopathies and outline the rationale for moving toward an earlier, biology-anchored definition of these disorders, with or without the presence of clinical symptoms. We underscore the utility of the αSyn seed amplification assay to detect aggregated αSyn in living patients and to differentiate between neuronal or glial αSyn pathology. We anticipate that a biological definition of synucleinopathies, if well-integrated with the current clinical classifications, will enable further understanding of the disease pathogenesis and contribute to the development of effective, disease-modifying therapies.

Keywords

Humans, alpha-Synuclein, Synucleinopathies, Neuroglia, Neurons, Parkinson Disease, Lewy Body Disease, Multiple System Atrophy, Brain, Animals

Published Open-Access

yes

Recommended Citation

Soto, Claudio; Mollenhauer, Brit; Hansson, Oskar; et al., "Toward a Biological Definition of Neuronal and Glial Synucleinopathies" (2025). Faculty, Staff and Student Publications. 6557.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6557