TY  - JOUR
AU  - Siderowf, Andrew
AU  - Concha-Marambio, Luis
AU  - Lafontant, David-Erick
AU  - Farris, Carly M
AU  - Ma, Yihua
AU  - Urenia, Paula A
AU  - Nguyen, Hieu
AU  - Alcalay, Roy N
AU  - Chahine, Lana M
AU  - Foroud, Tatiana
AU  - Galasko, Douglas
AU  - Kieburtz, Karl
AU  - Merchant, Kalpana
AU  - Mollenhauer, Brit
AU  - Poston, Kathleen L
AU  - Seibyl, John
AU  - Simuni, Tanya
AU  - Tanner, Caroline M
AU  - Weintraub, Daniel
AU  - Videnovic, Aleksandar
AU  - Choi, Seung Ho
AU  - Kurth, Ryan
AU  - Caspell-Garcia, Chelsea
AU  - Coffey, Christopher S
AU  - Frasier, Mark
AU  - Oliveira, Luis M A
AU  - Hutten, Samantha J
AU  - Sherer, Todd
AU  - Marek, Kenneth
AU  - Soto, Claudio
TI  - Assessment of heterogeneity among participants in the Parkinson's Progression Markers Initiative cohort using α-synuclein seed amplification: a cross-sectional study.
JO  - The lancet  / Neurology
VL  - 22
IS  - 5
SN  - 1474-4422
CY  - London
PB  - Lancet Publ. Group
M1  - DZNE-2023-00475
SP  - 407 - 417
PY  - 2023
AB  - Emerging evidence shows that α-synuclein seed amplification assays (SAAs) have the potential to differentiate people with Parkinson's disease from healthy controls. We used the well characterised, multicentre Parkinson's Progression Markers Initiative (PPMI) cohort to further assess the diagnostic performance of the α-synuclein SAA and to examine whether the assay identifies heterogeneity among patients and enables the early identification of at-risk groups.This cross-sectional analysis is based on assessments done at enrolment for PPMI participants (including people with sporadic Parkinson's disease from LRRK2 and GBA variants, healthy controls, prodromal individuals with either rapid eye movement sleep behaviour disorder (RBD) or hyposmia, and non-manifesting carriers of LRRK2 and GBA variants) from 33 participating academic neurology outpatient practices worldwide (in Austria, Canada, France, Germany, Greece, Israel, Italy, the Netherlands, Norway, Spain, the UK, and the USA). α-synuclein SAA analysis of CSF was performed using previously described methods. We assessed the sensitivity and specificity of the α-synuclein SAA in participants with Parkinson's disease and healthy controls, including subgroups based on genetic and clinical features. We established the frequency of positive α-synuclein SAA results in prodromal participants (RBD and hyposmia) and non-manifesting carriers of genetic variants associated with Parkinson's disease, and compared α-synuclein SAA to clinical measures and other biomarkers. We used odds ratio estimates with 95
KW  - Humans
KW  - alpha-Synuclein: genetics
KW  - Parkinson Disease: diagnosis
KW  - Parkinson Disease: genetics
KW  - Cross-Sectional Studies
KW  - Anosmia
KW  - REM Sleep Behavior Disorder
KW  - Biomarkers
KW  - alpha-Synuclein (NLM Chemicals)
KW  - Biomarkers (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C2  - pmc:PMC10627170
C6  - pmid:37059509
DO  - DOI:10.1016/S1474-4422(23)00109-6
UR  - https://pub.dzne.de/record/257678
ER  -