{"doi":"10.1093/brain/awae329","title":"Neurodegenerative fluid biomarkers are enriched in human cervical lymph nodes","abstract":"In animal models, brain neurodegeneration biomarkers drain into cervical lymph nodes (CLNs), and this drainage function is reduced with ageing. If this occurred in humans, CLNs may provide a readily accessible measure of this aspect of protein clearance. We tested this hypothesis in people using ultrasound-guided fine needle aspiration. We measured amyloid-beta 40 and 42, phosphorylated tau 181 (pTau181), glial fibrillary acidic protein and neurofilament light using single molecule array in CLN aspirates and plasma from: (i) a discovery cohort of 25 autoimmune patients; and (ii) plasma, CLNs and capillary blood in four healthy volunteers, an optimization cohort. Ultrasound-guided fine needle aspiration was well-tolerated by all participants. In both cohorts, all biomarkers were detected in all plasma and CLN samples, other than neurofilament light (8/17 of discovery cohort). CLN biomarker concentrations were significantly greater than plasma concentrations for all except neurofilament light, most markedly for pTau181 (266-fold; P < 0.02), whose CLN concentrations decreased with age (Spearman r = -0.66, P = 0.001). This study presents the first evidence that neurodegenerative biomarkers are detectable in human CLNs. Raised CLN:plasma biomarker ratios suggest their concentration in CLNs may offer a distinct compartment for minimally-invasive measurement of brain clearance and lymphatic drainage, with potential applicability to study of ageing and future clinical trials.","journal":"Brain","year":2024,"id":423115,"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":25,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9572,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":628809,"name":"Nicholas M. Provine","orcid":"0000-0002-9694-2216","position":1,"is_corresponding":false},{"id":1218138,"name":"Andrew G. Murchison","orcid":"0000-0001-8886-9891","position":2,"is_corresponding":false},{"id":1010583,"name":"Rhiannon Laban","orcid":"0000-0002-5926-8357","position":3,"is_corresponding":false},{"id":1218139,"name":"Owen Swann","orcid":"0000-0002-1464-0274","position":4,"is_corresponding":false},{"id":395841,"name":"Ivan Koychev","orcid":"0000-0001-6813-8493","position":5,"is_corresponding":false},{"id":1218140,"name":"Fintan Sheerin","orcid":"0000-0002-9891-7612","position":6,"is_corresponding":false},{"id":617547,"name":"Sandro Dá Mesquita","orcid":"0000-0002-0786-5010","position":7,"is_corresponding":false},{"id":379266,"name":"Amanda Heslegrave","orcid":"0000-0002-7290-6405","position":8,"is_corresponding":false},{"id":27601,"name":"Henrik Zetterberg","orcid":"0000-0003-3930-4354","position":9,"is_corresponding":false},{"id":106117,"name":"Paul Klenerman","orcid":"0000-0003-4307-9161","position":10,"is_corresponding":false},{"id":236508,"name":"Sarosh R. Irani","orcid":"0000-0002-7667-9748","position":11,"is_corresponding":false},{"id":1218137,"name":"Adam Al‐Diwani","orcid":"0000-0001-6596-7579","position":0,"is_corresponding":true}],"reference_count":30,"raw_metadata":null,"created_at":"2026-07-19T01:57:56.814994Z","pmid":"39432679","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":[]}