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000276802 1001_ $$00000-0002-3412-0524$$aSoto, Claudio$$b0
000276802 245__ $$aToward a biological definition of neuronal and glial synucleinopathies.
000276802 260__ $$a[New York, NY]$$bSpringer Nature$$c2025
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000276802 520__ $$aCerebral 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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000276802 650_7 $$2NLM Chemicals$$aalpha-Synuclein
000276802 650_2 $$2MeSH$$aHumans
000276802 650_2 $$2MeSH$$aNeuroglia: pathology
000276802 650_2 $$2MeSH$$aNeuroglia: metabolism
000276802 650_2 $$2MeSH$$aalpha-Synuclein: metabolism
000276802 650_2 $$2MeSH$$aalpha-Synuclein: genetics
000276802 650_2 $$2MeSH$$aSynucleinopathies: pathology
000276802 650_2 $$2MeSH$$aSynucleinopathies: metabolism
000276802 650_2 $$2MeSH$$aNeurons: pathology
000276802 650_2 $$2MeSH$$aNeurons: metabolism
000276802 650_2 $$2MeSH$$aParkinson Disease: pathology
000276802 650_2 $$2MeSH$$aParkinson Disease: genetics
000276802 650_2 $$2MeSH$$aParkinson Disease: metabolism
000276802 650_2 $$2MeSH$$aBrain: pathology
000276802 650_2 $$2MeSH$$aBrain: metabolism
000276802 650_2 $$2MeSH$$aMultiple System Atrophy: pathology
000276802 650_2 $$2MeSH$$aMultiple System Atrophy: metabolism
000276802 650_2 $$2MeSH$$aMultiple System Atrophy: genetics
000276802 650_2 $$2MeSH$$aLewy Body Disease: pathology
000276802 650_2 $$2MeSH$$aLewy Body Disease: metabolism
000276802 650_2 $$2MeSH$$aLewy Body Disease: genetics
000276802 7001_ $$0P:(DE-2719)9001340$$aMollenhauer, Brit$$b1$$udzne
000276802 7001_ $$00000-0001-8467-7286$$aHansson, Oskar$$b2
000276802 7001_ $$00000-0002-5970-6839$$aKang, Un Jung$$b3
000276802 7001_ $$00000-0002-5717-4875$$aAlcalay, Roy N$$b4
000276802 7001_ $$00000-0003-2921-8348$$aStandaert, David$$b5
000276802 7001_ $$00000-0001-6407-1199$$aTrenkwalder, Claudia$$b6
000276802 7001_ $$aMarek, Kenneth$$b7
000276802 7001_ $$aGalasko, Douglas$$b8
000276802 7001_ $$00000-0003-3424-7143$$aPoston, Kathleen$$b9
000276802 773__ $$0PERI:(DE-600)1484517-9$$a10.1038/s41591-024-03469-7$$gVol. 31, no. 2, p. 396 - 408$$n2$$p396 - 408$$tNature medicine$$v31$$x1078-8956$$y2025
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