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Toward a biological definition of neuronal and glial synucleinopathies

Soto, Claudio ; Mollenhauer, Brit ; Hansson, Oskar LU orcid ; Kang, Un Jung ; Alcalay, Roy N. ; Standaert, David ; Trenkwalder, Claudia ; Marek, Kenneth ; Galasko, Douglas and Poston, Kathleen (2025) In Nature Medicine 31(2). p.396-408
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... (More)

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.

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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Medicine
volume
31
issue
2
article number
34
pages
13 pages
publisher
Nature Publishing Group
external identifiers
  • scopus:85217249905
  • pmid:39885358
ISSN
1078-8956
DOI
10.1038/s41591-024-03469-7
language
English
LU publication?
yes
id
05a95577-27f6-4726-abaf-32ccf0399ccb
date added to LUP
2025-04-09 11:05:27
date last changed
2025-07-17 02:33:34
@article{05a95577-27f6-4726-abaf-32ccf0399ccb,
  abstract     = {{<p>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.</p>}},
  author       = {{Soto, Claudio and Mollenhauer, Brit and Hansson, Oskar and Kang, Un Jung and Alcalay, Roy N. and Standaert, David and Trenkwalder, Claudia and Marek, Kenneth and Galasko, Douglas and Poston, Kathleen}},
  issn         = {{1078-8956}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{396--408}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Medicine}},
  title        = {{Toward a biological definition of neuronal and glial synucleinopathies}},
  url          = {{http://dx.doi.org/10.1038/s41591-024-03469-7}},
  doi          = {{10.1038/s41591-024-03469-7}},
  volume       = {{31}},
  year         = {{2025}},
}