Evidence for lymphatic Aβ clearance in Alzheimer's transgenic mice
Open accessAbstract
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 15.5months, 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 6months 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.
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In a murine Alzheimer disease model, amyloid-β is present at high concentrations in cervical and axillary lymph nodes, at levels analogous to brain, and is undetectable or barely detectable in spleen and other peripheral tissues.
“in a murine model of Alzheimer disease, amyloid-b was present in high concentrations in the cervical and axillary lymph nodes, at levels analogous to those in the brain, and yet was either undetectable or barely so in the spleen and other peripheral tissues (47).”
From Glymphatic failure as a final common pathway to dementia (2020) · cites this paper as [47]
A large proportion of brain waste proteins and metabolites might pass through and be cleared by cervical lymphatics.
“Accordingly, a large proportion of brain waste proteins and metabolites might then be expected to pass through, and be cleared, by the cervical lymphatics.”
From Glymphatic failure as a final common pathway to dementia (2020) · cites this paper as [47]
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Self-citation
- Authors
- Pappolla, M., Sambamurti, K., Vidal, R., Pacheco-Quinto, J., Poeggeler, B., & Matsubara, E.
- Affiliations
- The University of Texas Medical Branch at Galveston (US)
- Medical University of South Carolina (US)
- Hirosaki University (JP)
- Corresponding author
- Pappolla, Miguel
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2014-11
- Volume
- 71
- Pages
- 215-219
- ISSN
- 0969-9961 (ISSN-L)
- PMC
- PMC5589075
- OpenAlex
- W2089819885
- Cited by
- 69
- References
- 33
- Citations by year
- 2026: 8 · 2025: 6 · 2024: 9 · 2023: 4 · 2022: 6 · 2021: 8 · 2020: 3 · 2019: 8 · 2018: 4 · 2017: 5 · 2016: 3 · 2015: 5
- FWCI
- 2.88
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- IUScholarWorks (Indiana University) (submittedVersion)
- PMC
- Funders
- NIH (AG046200, AG016783)
- Alzheimer's Association for IIRG (10-173180 and Zenith award to MAP)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- amyloid-beta clearance, lymphatic drainage, Alzheimer's disease, transgenic mice, cervical lymph nodes, axillary lymph nodes, Aβ40, amyloid-beta 42, plasma amyloid-beta, lymphatic system
- MeSH terms
- Alzheimer Disease, Animals, Brain, Humans, Lymph Nodes, Mice, Transgenic, Pyrrolidonecarboxylic Acid, Time Factors, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Mice, Presenilin-1
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