{"doi":"10.1002/mds.29524","title":"Plasma Neurofilament Light Chain Is Elevated in Adaptor Protein Complex <scp>4‐Related</scp> Hereditary Spastic Paraplegia","abstract":"BACKGROUND: Adaptor protein complex 4-associated hereditary spastic paraplegia (AP-4-HSP) is caused by pathogenic biallelic variants in AP4B1, AP4M1, AP4E1, and AP4S1. OBJECTIVE: The aim was to explore blood markers of neuroaxonal damage in AP-4-HSP. METHODS: Plasma neurofilament light chain (pNfL) and glial fibrillary acidic protein (GFAP) levels were measured in samples from patients and age- and sex-matched controls (NfL: n = 46 vs. n = 46; GFAP: n = 14 vs. n = 21) using single-molecule array assays. Patients' phenotypes were systematically assessed using the AP-4-HSP natural history study questionnaires, the Spastic Paraplegia Rating Scale, and the SPATAX disability score. RESULTS: pNfL levels increased in AP-4-HSP patients, allowing differentiation from controls (Mann-Whitney U test: P = 3.0e-10; area under the curve = 0.87 with a 95% confidence interval of 0.80-0.94). Phenotypic cluster analyses revealed a subgroup of individuals with severe generalized-onset seizures and developmental stagnation, who showed differentially higher pNfL levels (Mann-Whitney U test between two identified clusters: P = 2.5e-6). Plasma GFAP levels were unchanged in patients with AP-4-HSP. CONCLUSIONS: pNfL is a potential disease marker in AP-4-HSP and can help differentiate between phenotypic subgroups. © 2023 International Parkinson and Movement Disorder Society.","journal":"Movement Disorders","year":2023,"id":358612,"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":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9406,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":879690,"name":"Afshin Saffari","orcid":"0000-0003-4119-7519","position":1,"is_corresponding":false},{"id":771407,"name":"M. L. ZIEGLER","orcid":"0000-0002-0504-7815","position":2,"is_corresponding":false},{"id":767001,"name":"Catherine Jordan","orcid":"0000-0003-0099-1142","position":3,"is_corresponding":false},{"id":304201,"name":"Amy Tam","orcid":"0000-0003-2072-3436","position":4,"is_corresponding":false},{"id":1109007,"name":"So Young Kim","orcid":"0000-0002-5651-3046","position":5,"is_corresponding":false},{"id":419882,"name":"Edward Leung","orcid":"0000-0003-3154-2403","position":6,"is_corresponding":false},{"id":323133,"name":"Krzysztof Szczałuba","orcid":"0000-0001-8803-646X","position":7,"is_corresponding":false},{"id":924518,"name":"Hanna Mierzewska","orcid":"0000-0002-3255-6754","position":8,"is_corresponding":false},{"id":886565,"name":"Staci D. King","orcid":null,"position":9,"is_corresponding":false},{"id":301282,"name":"Filippo M. Santorelli","orcid":"0000-0002-1359-9062","position":10,"is_corresponding":false},{"id":360995,"name":"Grace Yoon","orcid":"0000-0002-3450-3293","position":11,"is_corresponding":false},{"id":310919,"name":"Bianca A. Trombetta","orcid":"0000-0001-7501-0666","position":12,"is_corresponding":false},{"id":366456,"name":"Pia Kivisäkk","orcid":"0000-0001-9708-7509","position":13,"is_corresponding":false},{"id":447518,"name":"Bo Zhang","orcid":"0000-0003-1574-198X","position":14,"is_corresponding":false},{"id":40872,"name":"Mustafa Sahin","orcid":"0000-0001-7044-2953","position":15,"is_corresponding":false},{"id":584752,"name":"Darius Ebrahimi‐Fakhari","orcid":"0000-0002-0026-4714","position":16,"is_corresponding":false},{"id":767002,"name":"Julian E. Alecu","orcid":"0000-0002-1420-9775","position":0,"is_corresponding":true}],"reference_count":37,"raw_metadata":null,"created_at":"2026-07-19T01:13:48.379546Z","pmid":"37482941","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":[]}