{"doi":"10.1002/mds.28667","title":"<scp>α‐Synuclein</scp> Deposition in Sympathetic Nerve Fibers in Genetic Forms of Parkinson's Disease","abstract":"BACKGROUND: Cytoplasmic inclusions of α-synuclein (α-syn) in brainstem neurons are characteristic of idiopathic Parkinson's disease (PD). PD also entails α-syn buildup in sympathetic nerves. Among genetic forms of PD, the relative extents of sympathetic intraneuronal accumulation of α-syn have not been reported. OBJECTIVE: This cross-sectional observational study compared magnitudes of intraneuronal deposition of α-syn in common and rare genetic forms of PD. METHODS: α-Syn deposition was quantified by the α-syn-tyrosine hydroxylase colocalization index in C2 cervical skin biopsies from 65 subjects. These included 30 subjects with pathogenic mutations in SNCA (n = 3), PRKN [biallelic (n = 7) and monoallelic (n = 3)], LRRK2 (n = 7), GBA (n = 7), or PARK7/DJ1 [biallelic (n = 1) and monoallelic (n = 2)]. Twenty-five of the mutation carriers had PD and five did not. Data were also analyzed from 19 patients with idiopathic PD and 16 control participants. RESULTS: α-Syn deposition varied as a function of genotype (F = 16.7, P < 0.0001). It was above the control range in 100% of subjects with SNCA mutations, 100% with LRRK2 mutations, 95% with idiopathic PD, 83% with GBA mutations, and 0% with biallelic PRKN mutations. α-Syn deposition in the biallelic PRKN group was significantly higher than in the control group. In addition, patients with biallelic PRKN mutations had higher α-syn deposition than their unaffected siblings. CONCLUSIONS: Individuals with SNCA, DJ-1, LRRK2, or GBA mutations have substantial intraneuronal α-syn deposition in sympathetic noradrenergic nerves in skin biopsies, whereas those with biallelic PRKN mutations do not. Biallelic PRKN patients may have mildly increased α-syn deposition compared with control subjects. © 2021 International Parkinson and Movement Disorder Society.","journal":"Movement Disorders","year":2021,"id":170892,"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":27,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9707,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":258200,"name":"David S. Goldstein","orcid":"0000-0002-5709-9940","position":1,"is_corresponding":false},{"id":650247,"name":"William Zhu","orcid":"0000-0001-5121-1025","position":2,"is_corresponding":false},{"id":348811,"name":"Esther Yoon","orcid":"0000-0001-9378-3988","position":3,"is_corresponding":false},{"id":271546,"name":"Debra Ehrlich","orcid":"0000-0002-2663-6766","position":4,"is_corresponding":false},{"id":472282,"name":"Alice B. Schindler","orcid":null,"position":5,"is_corresponding":false},{"id":545972,"name":"Angela Kokkinis","orcid":"0009-0001-5683-1415","position":6,"is_corresponding":false},{"id":295304,"name":"Marya S. Sabir","orcid":"0000-0001-6333-4049","position":7,"is_corresponding":false},{"id":271284,"name":"Sonja W. Scholz","orcid":"0000-0002-6623-0429","position":8,"is_corresponding":false},{"id":230757,"name":"Sara Bandrés‐Ciga","orcid":"0000-0003-0056-1361","position":9,"is_corresponding":false},{"id":252390,"name":"Cornelis Blauwendraat","orcid":"0000-0001-9358-8111","position":10,"is_corresponding":false},{"id":49082,"name":"Pedro Gonzalez‐Alegre","orcid":"0000-0002-9887-2995","position":11,"is_corresponding":false},{"id":305684,"name":"Grisel Lopez","orcid":"0000-0001-7785-2197","position":12,"is_corresponding":false},{"id":305686,"name":"Ellen Sidransky","orcid":"0000-0002-3019-8500","position":13,"is_corresponding":false},{"id":299707,"name":"Derek P. Narendra","orcid":"0000-0002-8696-9108","position":14,"is_corresponding":false},{"id":704538,"name":"Risa Isonaka","orcid":"0000-0002-7289-8257","position":0,"is_corresponding":true}],"reference_count":40,"raw_metadata":null,"created_at":"2026-07-18T23:46:28.747384Z","pmid":"34076298","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":[]}