TY  - JOUR
AU  - Soto, Claudio
AU  - Mollenhauer, Brit
AU  - Hansson, Oskar
AU  - Kang, Un Jung
AU  - Alcalay, Roy N
AU  - Standaert, David
AU  - Trenkwalder, Claudia
AU  - Marek, Kenneth
AU  - Galasko, Douglas
AU  - Poston, Kathleen
TI  - Toward a biological definition of neuronal and glial synucleinopathies.
JO  - Nature medicine
VL  - 31
IS  - 2
SN  - 1078-8956
CY  - [New York, NY]
PB  - Springer Nature
M1  - DZNE-2025-00327
SP  - 396 - 408
PY  - 2025
AB  - 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.
KW  - Humans
KW  - Neuroglia: pathology
KW  - Neuroglia: metabolism
KW  - alpha-Synuclein: metabolism
KW  - alpha-Synuclein: genetics
KW  - Synucleinopathies: pathology
KW  - Synucleinopathies: metabolism
KW  - Neurons: pathology
KW  - Neurons: metabolism
KW  - Parkinson Disease: pathology
KW  - Parkinson Disease: genetics
KW  - Parkinson Disease: metabolism
KW  - Brain: pathology
KW  - Brain: metabolism
KW  - Multiple System Atrophy: pathology
KW  - Multiple System Atrophy: metabolism
KW  - Multiple System Atrophy: genetics
KW  - Lewy Body Disease: pathology
KW  - Lewy Body Disease: metabolism
KW  - Lewy Body Disease: genetics
KW  - alpha-Synuclein (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:39885358
DO  - DOI:10.1038/s41591-024-03469-7
UR  - https://pub.dzne.de/record/276802
ER  -