Tauopathy after long-term cervical lymphadenectomy.

Area of Science:

• Neurology
• Oncology
• Immunology

Background:

• Cervical lymphadenectomy (cLE) is a critical procedure for head and neck cancers.
• Millions undergo cLE annually, with potential long-term health implications.
• The neurological effects of cLE remain largely unexplored.

Purpose of the Study:

• To investigate the long-term effects of cLE on cognitive function and Alzheimer's disease (AD)-like tauopathy.
• To explore the underlying molecular mechanisms, including pathway activation and brain waste clearance.

Main Methods:

• Male C57BL/6 mice underwent long-term cLE.
• Sleep, brain pathways, and pathologies were assessed.
• RNA sequencing, proteomics, western blotting, and immunofluorescence were employed.

Main Results:

• cLE induced sleep and psychiatric disorders, associated with ERK pathway activation.
• ERK activation interfered with autophagy and promoted phosphorylated tau (p-tau) accumulation.
• Reduced clearance of brain waste (amyloid beta, p-tau) in peripheral blood post-cLE was observed, indicating impaired lymphatic drainage.

Conclusions:

• Long-term cLE is linked to cognitive impairment, anxiety-depressive disorders, and accelerated p-tau deposition in mice.
• Impaired lymphatic drainage and ERK pathway activation contribute to these neurological changes.
• Findings suggest a need for further evaluation of neurologic effects of cLE, impacting surgical considerations.