{"doi":"10.1101/2025.04.29.651203","title":"Targeted plasma proteomics uncover novel proteins associated with <i>KIF5A</i> -linked SPG10 and ALS spectrum disorders","abstract":"Abstract KIF5A (Kinesin family member 5A) is a motor protein that functions as a key component of the axonal transport machinery. Variants in KIF5A are linked to several neurodegenerative diseases, mainly spastic paraplegia type 10 (SPG10), Charcot-Marie-Tooth disease type 2 (CMT2), and amyotrophic lateral sclerosis (ALS). These diseases share motor neuron involvement but vary significantly in clinical presentation, severity, and progression. KIF5A variants are mainly categorized into N-terminal variants associated with SPG10/CMT2 and C-terminal variants linked to ALS. This study utilized a novel multiplex NULISA targeted platform to analyze plasma proteome from KIF5A -linked SPG10, ALS patients and compared to healthy controls. Our results revealed distinct proteomic signatures, with significant alterations in proteins related to synaptic function, and inflammation. Notably, neurofilament light polypeptide, a biomarker for neurodegenerative diseases, was elevated in KIF5A ALS but not in SPG10 patients. Moreover, these findings can now be taken forward to gain mechanistic understanding of axonopathies linking to N- vs C-terminal KIF5A variants affecting both central and peripheral nervous systems.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":565217,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9627,"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":244964,"name":"Arun K. Boddapati","orcid":"0000-0002-7661-8443","position":1,"is_corresponding":false},{"id":241687,"name":"Barbara Risi","orcid":"0009-0008-2303-1180","position":2,"is_corresponding":false},{"id":1243299,"name":"Pablo Iruzubieta","orcid":"0000-0003-0331-6222","position":3,"is_corresponding":false},{"id":1468712,"name":"Antonio Orlacchio","orcid":"0000-0002-2602-3281","position":4,"is_corresponding":false},{"id":1468713,"name":"Roberto Fernández‐Torrón","orcid":"0000-0002-2202-8165","position":5,"is_corresponding":false},{"id":840120,"name":"Tamara Castillo‐Triviño","orcid":"0000-0002-9249-3185","position":6,"is_corresponding":false},{"id":847083,"name":"Adolfo López de Munain","orcid":null,"position":7,"is_corresponding":false},{"id":1468714,"name":"Steve Vucic","orcid":"0000-0002-0956-4633","position":8,"is_corresponding":false},{"id":522390,"name":"Laura Donker Kaat","orcid":"0009-0007-2436-0931","position":9,"is_corresponding":false},{"id":56960,"name":"Tahsin Stefan Barakat","orcid":"0000-0003-1231-1562","position":10,"is_corresponding":false},{"id":228616,"name":"Leonard Petrucelli","orcid":"0000-0003-2959-129X","position":11,"is_corresponding":false},{"id":238155,"name":"Mercedes Prudencio","orcid":"0000-0002-4894-4858","position":12,"is_corresponding":false},{"id":291677,"name":"John E. Landers","orcid":"0000-0001-8084-5043","position":13,"is_corresponding":false},{"id":486806,"name":"Jochen H. Weishaupt","orcid":"0000-0002-3399-9784","position":14,"is_corresponding":false},{"id":668313,"name":"Andreas Prokop","orcid":"0000-0001-8482-3298","position":15,"is_corresponding":false},{"id":241678,"name":"Massimiliano Filosto","orcid":"0000-0002-2852-7512","position":16,"is_corresponding":false},{"id":17548,"name":"Zbigniew K. Wszołek","orcid":"0000-0001-5487-1053","position":17,"is_corresponding":false},{"id":487009,"name":"Devesh C. Pant","orcid":"0000-0003-4046-4195","position":18,"is_corresponding":false},{"id":733633,"name":"Jarosław Dulski","orcid":"0000-0002-5517-9875","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:56:28.709936Z","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":[]}