The Potential Connection Between the Brain and Neck: Exploring the Meningeal-Cervical Lymphatic Pathway in Primate Models.

Abstract

There is burgeoning interest in the role of lymphatic drainage in Alzheimer's Disease. The brain was historically regarded as an immune-privileged organ devoid of lymphatic drainage. Recent discoveries of the glymphatic and meningeal lymphatic systems have challenged this view, suggesting that cerebrospinal fluid (CSF) and interstitial waste may drain into the deep cervical lymph nodes (dcLN). However, this pathway has not been conclusively demonstrated in non-human primates. Two Non-Human Primates (NHPs) (Macaca fascicularis species) underwent craniotomy with catheter insertion into the subarachnoid space. Indocyanine green (ICG) was injected intracranially and tracked using near-infrared (NIR) imaging. In both NHPs, ICG was detected in the peri-jugular dcLN within an average of 613.5 seconds post-injection. This study provides the first in vivo primate evidence of a potential meningeal lymphatic drainage pathway to the dcLN, supporting its anatomical and functional relevance. Our findings suggest that dcLNs may facilitate clearance of neuropathological proteins. The use of a clinically ubiquitous imaging agent like ICG underscores its translational potential in future human studies.