Cervical Lymph Nodes Contain Elevated Neurodegenerative Biomarkers in Humans

Overview

This study demonstrates that neurodegenerative fluid biomarkers, including amyloid-beta and phosphorylated tau, are detectable at significantly higher concentrations in human cervical lymph nodes (CLNs) compared to plasma. The findings suggest that CLNs serve as a distinct compartment reflecting brain protein clearance and lymphatic drainage, with potential applications in aging and dementia research.

Background

Neurodegenerative diseases such as Alzheimer's disease are characterized by accumulation of abnormal proteins like amyloid-beta plaques and hyper-phosphorylated tau tangles in the brain. These biomarkers can be measured in cerebrospinal fluid and blood, aiding diagnosis and monitoring. Animal studies have shown that brain clearance of these proteins involves glymphatic and meningeal lymphatic systems draining into cervical lymph nodes. However, direct biochemical assessment of this drainage in humans has been challenging due to intracranial anatomy. Sampling CLNs via ultrasound-guided fine needle aspiration offers a minimally invasive approach to study this system.

Data Highlights

Key Findings

• All tested neurodegenerative biomarkers were detectable in both plasma and CLN aspirates, except neurofilament light which was less frequently detected in plasma.
• CLN concentrations of amyloid-beta 40/42, phosphorylated tau 181, and glial fibrillary acidic protein were significantly higher than plasma levels.
• Phosphorylated tau 181 showed the most marked enrichment in CLNs, with a 266-fold increase compared to plasma.
• Phosphorylated tau 181 levels in CLNs decreased with increasing age (Spearman r = -0.66, P = 0.001).
• Ultrasound-guided fine needle aspiration of CLNs was well tolerated and feasible in both autoimmune patients and healthy volunteers.
• These findings provide the first evidence that human CLNs contain neurodegenerative fluid biomarkers, supporting their role in brain protein clearance pathways.

Clinical Implications

Sampling cervical lymph nodes via fine needle aspiration offers a minimally invasive method to assess brain clearance of neurodegenerative proteins, potentially complementing cerebrospinal fluid and blood biomarker analyses. This approach may facilitate monitoring of disease progression and therapeutic response in dementia, and provide insights into aging-related changes in brain protein clearance.

Conclusion

Human cervical lymph nodes contain elevated levels of key neurodegenerative biomarkers compared to plasma, reflecting their role in brain protein clearance and lymphatic drainage. This novel sampling approach holds promise for advancing biomarker research and clinical monitoring in neurodegenerative diseases.

References

1. Authors et al. 2024 -- Cervical Lymph Nodes Show Increased Levels of Neurodegenerative Fluid Biomarkers in Humans