Neurodegenerative fluid biomarkers are enriched in human cervical lymph nodes
Neurodegenerative fluid biomarkers are enriched in human cervical lymph nodes
Abstract In animal models, brain neurodegeneration biomarkers drain into cervical lymph nodes (CLNs). If this occurred in humans, CLNs may provide a readily accessible source of these biomarkers, draining the site of primary pathology. We tested this hypothesis in discovery and validation cohorts using ultrasound-guided fine needle aspiration (FNA). We measured amyloid-beta 40 and 42, phospho-Tau-181, 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 from ii) plasma, CLNs and capillary blood in four healthy volunteers, an optimisation-validation cohort. FNA was well-tolerated by all participants. In both cohorts, all biomarkers were detected in all plasmas and CLNs, 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 phospho-Tau-181 (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, which may offer a sensitive compartment for minimally-invasive sampling in clinical trials. Further, age-associated phospho-Tau-181 reduction with age suggests FNA of CLNs may measure the integrity of brain lymphatic drainage in vivo.
Klenerman Paul、Laban Rhiannon、Swann Owen J、Koychev Ivan、Da Mesquita Sandro、Irani Sarosh R、Zetterberg Henrik、Provine Nicholas M、Al-Diwani Adam、Heslegrave Amanda、Murchison Andrew、Sheerin Fintan
Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford||Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford||Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of OxfordUK Dementia Research Institute, Fluid Biomarker LaboratoryUK Dementia Research Institute, Fluid Biomarker LaboratoryDepartment of Psychiatry, University of OxfordDepartment of Neuroscience, Mayo ClinicDepartment of Neuroscience, Mayo Clinic||Oxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford||Department of Neurology, Mayo ClinicUK Dementia Research Institute, Fluid Biomarker Laboratory||Department of Neurodegenerative Disease, UCL Institute of Neurology||Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg||Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital||Hong Kong Center for Neurodegenerative Diseases||Wisconsin Alzheimer?ˉs Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-MadisonPandemic Sciences Institute, Nuffield Department of Medicine, University of OxfordDepartment of Psychiatry, University of OxfordUK Dementia Research Institute, Fluid Biomarker Laboratory||Department of Neurodegenerative Disease, UCL Institute of NeurologyDepartment of Radiology, Oxford University HospitalsDepartment of Radiology, Oxford University Hospitals
神经病学、精神病学基础医学医学研究方法
Klenerman Paul,Laban Rhiannon,Swann Owen J,Koychev Ivan,Da Mesquita Sandro,Irani Sarosh R,Zetterberg Henrik,Provine Nicholas M,Al-Diwani Adam,Heslegrave Amanda,Murchison Andrew,Sheerin Fintan.Neurodegenerative fluid biomarkers are enriched in human cervical lymph nodes[EB/OL].(2025-03-28)[2025-04-28].https://www.biorxiv.org/content/10.1101/2024.04.26.591238.点此复制
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