Journal Article (Review Article)

DZNE-2025-00327

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Toward a biological definition of neuronal and glial synucleinopathies.

Soto, C. ; Mollenhauer, B.DZNE* ; Hansson, O. ; Kang, U. J. ; Alcalay, R. N. ; Standaert, D. ; Trenkwalder, C. ; Marek, K. ; Galasko, D. ; Poston, K.

2025
Springer Nature [New York, NY]

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Please use a persistent id in citations: doi:10.1038/s41591-024-03469-7

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.

Keyword(s): Humans (MeSH) ; Neuroglia: pathology (MeSH) ; Neuroglia: metabolism (MeSH) ; alpha-Synuclein: metabolism (MeSH) ; alpha-Synuclein: genetics (MeSH) ; Synucleinopathies: pathology (MeSH) ; Synucleinopathies: metabolism (MeSH) ; Neurons: pathology (MeSH) ; Neurons: metabolism (MeSH) ; Parkinson Disease: pathology (MeSH) ; Parkinson Disease: genetics (MeSH) ; Parkinson Disease: metabolism (MeSH) ; Brain: pathology (MeSH) ; Brain: metabolism (MeSH) ; Multiple System Atrophy: pathology (MeSH) ; Multiple System Atrophy: metabolism (MeSH) ; Multiple System Atrophy: genetics (MeSH) ; Lewy Body Disease: pathology (MeSH) ; Lewy Body Disease: metabolism (MeSH) ; Lewy Body Disease: genetics (MeSH) ; alpha-Synuclein

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Contributing Institute(s):

1. Epigenetics and Systems Medicine in Neurodegenerative Diseases (AG Fischer)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2025

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; DEAL Nature ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 80 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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