{"doi":"10.1101/2022.05.05.22274567","title":"PERFORMANCE OF αSYNUCLEIN RT-QUIC IN RELATION TO NEUROPATHOLOGICAL STAGING OF LEWY BODY DISEASE","abstract":"Abstract Currently, there is a need for diagnostic markers in Lewy body disorders (LBD). αSyn RT-QuIC has emerged as a promising assay to detect misfolded α-synuclein 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.","journal":"medRxiv","year":2022,"id":299227,"datarank":0.34055743562898955,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.09914174876387445,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.09914174876387445,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":3,"citers_with_citation_signal":3,"citers_with_endowment":3,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9509,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":227553,"name":"Christina D. Orrú","orcid":"0000-0001-7253-2944","position":1,"is_corresponding":false},{"id":256002,"name":"Geidy E. Serrano","orcid":"0000-0002-9527-2011","position":2,"is_corresponding":false},{"id":108599,"name":"Douglas Galasko","orcid":"0000-0001-6195-3241","position":3,"is_corresponding":false},{"id":227556,"name":"Andrew G. Hughson","orcid":"0000-0002-0725-4017","position":4,"is_corresponding":false},{"id":328503,"name":"Bradley R. Groveman","orcid":"0000-0002-5059-7672","position":5,"is_corresponding":false},{"id":250779,"name":"Charles H. Adler","orcid":"0000-0002-1045-2743","position":6,"is_corresponding":false},{"id":107088,"name":"Thomas G. Beach","orcid":"0000-0003-3296-6128","position":7,"is_corresponding":false},{"id":227561,"name":"Byron Caughey","orcid":"0000-0002-3928-6101","position":8,"is_corresponding":false},{"id":65584,"name":"Oskar Hansson","orcid":"0000-0001-8467-7286","position":9,"is_corresponding":false},{"id":847659,"name":"Sara Hall","orcid":"0000-0001-6585-9105","position":0,"is_corresponding":true}],"reference_count":62,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:31:44.904250Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}