A recent paper published in Neuron, from Weill Cornell Medicine and collaborating institutions, highlights that surgical removal of cervical lymph nodes may disrupt the brain's waste clearance, with consequences for cognitive health.

Khan, Clement et al. analyzed records from head and neck cancer patients who underwent neck lymphadenectomy without chemo-radiation. Up to 18% of patients under 65 developed mild-to-severe cognitive impairment within two years, three to four times the expected rate, and 25% did in those 65 and older. MRI showed faster temporal horn widening after bilateral surgery (17% per year) than unilateral surgery (4.2% per year).

To investigate the mechanism, the team modelled abrupt lymphatic disruption in mice and rats. Cerebrospinal fluid showed a signature of metabolic stress and mild inflammation, including activation of NAD⁺ and glutathione synthesis pathways. In the hippocampus, redox stress drove oxidative post-translational modifications and the formation of protein microaggregates. These were enriched in presynaptic and mitochondrial proteins, suggesting that synaptic regions are especially vulnerable to waste-induced stress.

PEAKS Studio and PEAKS Online were used for database searching and TMT-based quantification (PEAKS Q) of the CSF proteome, and for label-free quantitation of the 880 proteins identified in the isolated microaggregate fraction. PEAKS' PTM search capabilities were used to identify oxidative and glycation-related modifications and ubiquitination sites on the aggregated proteins, linking redox imbalance to protein damage at the site level. PEAKS Online was also used to analyse hippocampal DIA-PASEF data, enabling deep, label-free profiling of hippocampal tissue from ligated and sham mice, revealing 72 differentially expressed proteins

The aggregates differed in composition and modification profile from those seen in Alzheimer's disease and were absent when lymphatic drainage was reduced gradually. These findings link cognitive impairment after acute neck lymphadenectomy to impaired metabolic waste clearance. BSI is proud to see PEAKS support research that connects clinical observations to molecular mechanisms.

Read the full article here: Khan, Z.N., Clement, C.C., Roßmüller, P., …, Benveniste, H., Kipnis, J., Santambrogio, L. (2027) Cervical lymphadenectomy impairs brain lymphatic clearance and synaptic proteostasis. Neuron 115. doi:10.1016/j.neuron.2026.09.005