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Performance of αSyn...
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Hall, SaraLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital
(författare)
Performance of αSynuclein RT-QuIC in relation to neuropathological staging of Lewy body disease
- Artikel/kapitelEngelska2022
Förlag, utgivningsår, omfång ...
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2022-06-22
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Springer Science and Business Media LLC,2022
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LIBRIS-ID:oai:lup.lub.lu.se:2d746097-c7cb-44ba-aadb-021c6dcc3c6c
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https://lup.lub.lu.se/record/2d746097-c7cb-44ba-aadb-021c6dcc3c6cURI
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https://doi.org/10.1186/s40478-022-01388-7DOI
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Språk:engelska
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Sammanfattning på:engelska
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Currently, there is a need for diagnostic markers in Lewy body disorders (LBD). α-synuclein (αSyn) RT-QuIC has emerged as a promising assay to detect misfolded αSyn in clinically or neuropathologically established patients with various synucleinopathies. In this study, αSyn RT-QuIC was used to analyze lumbar CSF in a clinical cohort from the Swedish BioFINDER study and postmortem ventricular CSF in a neuropathological cohort from the Arizona Study of Aging and Neurodegenerative Disorders/Brain and Body Donation Program (AZSAND/BBDP). The BioFINDER cohort included 64 PD/PDD, 15 MSA, 15 PSP, 47 controls and two controls who later converted to PD/DLB. The neuropathological cohort included 101 cases with different brain disorders, including LBD and controls. In the BioFINDER cohort αSyn RT-QuIC identified LBD (i.e. PD, PDD and converters) vs. controls with a sensitivity of 95% and a specificity of 83%. The two controls that converted to LBD were αSyn RT-QuIC positive. Within the AZSAND/BBDP cohort, αSyn RT-QuIC identified neuropathologically verified "standard LBD" (i.e. PD, PD with AD and DLB; n = 25) vs. no LB pathology (n = 53) with high sensitivity (100%) and specificity (94%). Only 57% were αSyn RT-QuIC positive in the subgroup with "non-standard" LBD (i.e., AD with Lewy Bodies not meeting criteria for DLB or PD, and incidental LBD, n = 23). Furthermore, αSyn RT-QuIC reliably identified cases with LB pathology in the cortex (97% sensitivity) vs. cases with no LBs or LBs present only in the olfactory bulb (93% specificity). However, the sensitivity was low, only 50%, for cases with LB pathology restricted to the brainstem or amygdala, not affecting the allocortex or neocortex. In conclusion, αSyn RT-QuIC of CSF samples is highly sensitive and specific for identifying cases with clinicopathologically-defined Lewy body disorders and shows a lower sensitivity for non-standard LBD or asymptomatic LBD or in cases with modest LB pathology not affecting the cortex.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Orrù, Christina D.NIAID Rocky Mountain Laboratories
(författare)
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Serrano, Geidy E.Banner Sun Health Research Institute
(författare)
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Galasko, DouglasVA San Diego Healthcare System
(författare)
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Hughson, Andrew G.NIAID Rocky Mountain Laboratories
(författare)
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Groveman, Bradley R.NIAID Rocky Mountain Laboratories
(författare)
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Adler, Charles H.Mayo Clinic Scottsdale-Phoenix, Arizona
(författare)
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Beach, Thomas G.Banner Sun Health Research Institute
(författare)
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Caughey, ByronNIAID Rocky Mountain Laboratories
(författare)
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Hansson, OskarLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital(Swepub:lu)mphy-ohn
(författare)
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Klinisk minnesforskningForskargrupper vid Lunds universitet
(creator_code:org_t)
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Ingår i:Acta Neuropathologica Communications: Springer Science and Business Media LLC102051-5960
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Hall, Sara
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Galasko, Douglas
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Adler, Charles H ...
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Beach, Thomas G.
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Caughey, Byron
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Hansson, Oskar
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