{"doi":"10.1101/2025.10.01.25337085","title":"Clinical and imaging characteristics of Parkinson’s disease with negative alpha-synuclein seed amplification assay","abstract":"Abstract Background The CSF alpha-synuclein seed amplification assay (CSFasynSAA) detects alpha-synuclein aggregation in over 90% of individuals with sporadic PD (sPD). However, the clinical characteristics of sPD with negative CSFasynSAA remain undefined. Objectives Describe clinical and neuroimaging characteristics of CSFasynSAA negative sPD individuals in the Parkinson’s Progression Markers Initiative (PPMI). Methods We identified sPD PPMI participants with a negative CSFasynSAA (SAA negative, n=80) or positive CSFasynSAA (SAA positive, n=856) result at baseline. For comparative analysis between groups we used a reduced dataset (n=79 SAA negative and n=237 SAA positive) propensity-score matched on age, sex, and time since clinical diagnosis. Clinical parameters, DAT-SPECT, and MRI brain volumetrics were analyzed. Results The SAA negative and matched SAA positive groups had similar motor performance on the MDS-UPDRS-part III and similar cognitive performance on the MoCA at baseline. The proportion with severe hyposmia was 12% for SAA negative versus 73% for SAA positive ( p < 0.001). Per PPMI enrollment criteria all participants were classified as having an abnormal DAT-SPECT. There were no significant differences in median quantitative DAT-SPECT measures between groups. The SAA negative group showed a higher degree of atrophy in subcortical brain regions including substantia nigra. Longitudinally, 14.3% of SAA negative participants had a change in diagnosis, versus 0.9% of SAA positive participants. Conclusions At baseline, SAA negative sPD PPMI participants have a substantially lower rate of hyposmia, but otherwise cannot be readily distinguished from SAA positive participants based on clinical characteristics. However, SAA negative participants have a greater degree of subcortical brain atrophy, and approximately 1 out of 6 SAA negative participants received a change in diagnosis.","journal":"medRxiv","year":2025,"id":559210,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9569,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1460429,"name":"Jacopo Pasquini","orcid":"0000-0003-1856-2995","position":1,"is_corresponding":false},{"id":597433,"name":"Seung Ho Choi","orcid":"0000-0002-9834-9926","position":2,"is_corresponding":false},{"id":906274,"name":"David-Erick Lafontant","orcid":"0000-0003-2157-7151","position":3,"is_corresponding":false},{"id":48826,"name":"Seyed‐Mohammad Fereshtehnejad","orcid":"0000-0001-9255-9351","position":4,"is_corresponding":false},{"id":445140,"name":"Yashar Zeighami","orcid":"0000-0002-0583-5811","position":5,"is_corresponding":false},{"id":1230442,"name":"Piergiorgio Grillo","orcid":"0000-0001-8196-3914","position":6,"is_corresponding":false},{"id":661645,"name":"Giulietta Riboldi","orcid":"0000-0003-0322-5718","position":7,"is_corresponding":false},{"id":1460430,"name":"Houman Azizi","orcid":"0009-0001-3593-5231","position":8,"is_corresponding":false},{"id":1176911,"name":"Roqaie Moqadam","orcid":"0000-0003-0361-3083","position":9,"is_corresponding":false},{"id":255912,"name":"Un Jung Kang","orcid":"0000-0002-5970-6839","position":10,"is_corresponding":false},{"id":1461007,"name":"Kelly N.H. 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