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Alzheimer’s Disease, the main cause of dementia, is defined by a build-up of particular proteins in the brain which can spread and cause brain shrinkage affecting memory, thinking, and behaviour. Now, a team led by scientists at the Department of Psychiatry at the University of Oxford, supported by the National Institute for Health and Care Research (NIHR) Oxford Health Biomedical Research Centre (BRC), have discovered the presence of these proteins in cervical lymph nodes in the neck.
Significantly, more of the proteins were present in the lymph nodes of younger people than older people, suggesting that they drain away less well from the brain in older adults, potentially explaining the build-up that leads to Alzheimer’s Disease. This drainage mechanism has previously been explored in mouse models, but this is the first direct demonstration of these ‘brain bins’ in humans. The findings were published in the journal Brain.
Lead author Dr Adam Al-Diwani, NIHR Clinical Lecturer at the Department of Psychiatry at Oxford, is now managing a larger study to further test the idea. He said:
We have previously learned a lot about how cervical lymph nodes work as sites of immunity in encephalitis, here we wanted to explore their role in draining brain proteins as we age, the main risk factor for Alzheimer’s disease and dementia.”
The team worked with expert radiology doctors who use ultrasound to see exactly where the neck lymph nodes are. Then, using a very fine needle they safely target an accessible node just under the skin. This is a commonly used clinical procedure usually used for investigation of lumps and bumps. In their expert hands, the risk is no more than a blood test. The team have done qualitative follow-up over several studies over the past eight years which find that participants see lymph node sampling as both tolerable and acceptable for the research question in mind.
Dr Al-Diwani added: “We found high levels of proteins that usually define Alzheimer’s disease in lymph node samples from younger people. This supported the hypothesis that the lymph nodes act as a drainage basin from the brain. We then saw that this reduced in older people, suggesting that this was less effective with age. Together with previous animal studies, we see this as evidence that the cervical lymph nodes are acting as ‘bins for the brain’ – this study provides the first direct biochemical evidence of this in humans.”
This could have real significance for our understanding of the causes of Alzheimer’s disease, showing the potentially critical role of lymph nodes and our wider immune system in diseases of the brain.
“This could have real significance for our understanding of the causes of Alzheimer’s disease, showing the potentially critical role of lymph nodes and our wider immune system in diseases of the brain.
“More research is now needed to understand how and why this happens as we age, which is why we are keen to recruit more people to be part of our new, larger study. This could help understand the contribution of drainage to Alzheimer’s Disease risk, and also monitor the impact of new treatments targeted at improving drainage, and finally we will look at whether these drained proteins are driving immune responses which can protect the brain – this could potentially be harnessed to develop new treatments.”
Professor Paul Harrison, Associate Head of the Department of Psychiatry for Research and Lead of the Molecular Target theme at the Oxford Health BRC, said:
This is an exciting new way to explore how the brain is affected by diseases such as Alzheimer’s disease. It promises to provide new insights that may help us develop new treatments and monitor their effects.”
The new study, called Neuroimmune mechanisms in brain health – ‘ANIMATE’ – based in the NIHR Oxford Health BRC, needs around 60 participants, both healthy, younger people and older adults and those with emerging memory problems. The study involves undergoing the same lymph node sampling to test the significance of the findings in a larger group including those who are at higher and lower risk of Alzheimer’s disease. The team will seek to recruit participants from the Oxford brain health centre memory clinic and in collaboration with the Dementias Platform UK Great Minds research registry.
Email for more information about participating in the study.
A DPhil in Biomedical and Clinical Sciences (Oxford-GSK), funded by GSK (GlaxoSmithKline), is open for applications to work on this study. Apply. The deadline is Friday, March 14th at midday.