Evidence for lymphatic Aβ clearance in Alzheimer's transgenic mice

• This is the first demonstration of Aβ in lymph nodes of an AD transgenic mouse model.
• There was a time dependent increase in Aβ levels in lymph nodes, mirroring the increase of Aβ in the brain.
• Higher levels of Aβ were detected in lymph nodes than plasma.
• Lymphatic clearance is an overlooked pathway for removal of Aβ and may play a role in AD pathogenesis.

Evidence has shown that lymphatic drainage contributes to removal of debris from the brain but its role in the accumulation of amyloid β peptides (Aβ) has not been demonstrated. We examined the levels of various forms of Aβ in the brain, plasma and lymph nodes in a transgenic model of Alzheimer's disease (AD) at different ages. Herein, we report on the novel finding that Aβ is present in the cervical and axillary lymph nodes of AD transgenic mice and that Aβ levels in lymph nodes increase over time, mirroring the increase of Aβ levels observed in the brain. Aβ levels in lymph nodes were significantly higher than in plasma. At age 15.5 months, there was a significant increase of monomeric soluble Aβ40 (p = 0.003) and Aβ42 (p = 0.05) in the lymph nodes over the baseline values measured at 6 months of age. In contrast, plasma levels of Aβ40 showed no significant changes (p = 0.68) and plasma levels Aβ42 significantly dropped (p = 0.02) at the same age. Aβ concentration was low to undetectable in splenic lymphoid tissue and several other control tissues including heart, lung, liver, kidneys and intestine of the same animals, strongly suggesting that Aβ peptides in lymph nodes are derived from the brain.