Inflammation is usually a story about a swollen ankle. The brain has its own version, quieter and harder to see, and it is one of the most active areas of research in neuroscience and biochemistry. It also sits in the field where I work, so I will be careful to separate what is established from what is still being tested.
What neuroinflammation is
The brain is protected by the blood–brain barrier, but it is not sealed off from the immune system. Resident immune cells called microglia survey the tissue, clear debris and react to injury, infection and other signs of danger. Astrocytes take part as well. When these cells are activated they release cytokines, small signalling proteins, that call for help and change how neurons behave.
The key point from the reviews is that the response depends on context. Its duration, its strength and the type of trigger decide whether it helps or harms.1 A brief response clears an infection or repairs an injury. A persistent one, with no resolution, can wear on healthy tissue.
The pathway in three steps
- A sensor notices danger. Receptors such as Toll-like receptor 4 (TLR4) on microglia detect bacterial fragments and molecules released by damaged cells.
- A switch turns on the genes. The transcription factor NF-κB moves into the nucleus and activates genes for inflammatory proteins, including the inactive precursor of the messenger IL-1β. This is the priming step.
- An alarm assembles. A second signal triggers the NLRP3 inflammasome, which activates the enzyme caspase-1 and releases mature IL-1β. The mechanics are covered in The Inflammasome, Explained.
The sensor, the switch and the alarm are why researchers talk about a "TLR4/NF-κB/NLRP3 axis".2
What the mouse experiments showed
In 2013, Heneka and colleagues studied mice engineered to develop Alzheimer's-like disease. Mice that also lacked NLRP3 or caspase-1 were largely protected from the loss of spatial memory, had lower brain levels of active caspase-1 and IL-1β, and cleared more of the amyloid-β protein that accumulates in the disease.3 This does not show that blocking NLRP3 would treat people. It shows that the pathway is involved, in that model, in a measurable way.
Where diabetes comes in
People with diabetes have a higher risk of cognitive decline and dementia. The mechanisms under study include vascular damage, disturbed insulin signalling and inflammation, and they overlap.4 That overlap is why the diabetic brain is a natural place to look for inflammatory pathways, and it is part of the reason I work on it.
What is still unknown
Neuroinflammation is hard to measure in living people, and the picture changes with the stage of disease. Reviews of the Alzheimer's field describe microglial activation that looks different early and late, and conclude that the idea of "inflammation bad, switch it off" is too simple.5 Be cautious about claims that a food or supplement "fights brain inflammation". The evidence for specific products in people is thin, and the strongest results in the literature are in cells and animals.
What you can do today is dull and well supported in general: protect your sleep, which is the subject of What Sleep Does for Your Brain, and manage blood sugar if you have diabetes.
General information. This article is not medical advice. If you have diabetes or a memory concern, follow your doctor's guidance.
References
- DiSabato DJ, Quan N, Godbout JP. Neuroinflammation: the devil is in the details. J Neurochem. 2016;139(Suppl 2):136–153. Find it ↗
- Heneka MT, Kummer MP, Latz E. Innate immune activation in neurodegenerative disease. Nat Rev Immunol. 2014;14(7):463–477. Find it ↗
- Heneka MT, Kummer MP, Stutz A, et al. NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS1 mice. Nature. 2013;493(7434):674–678. Find it ↗
- Biessels GJ, Despa F. Cognitive decline and dementia in diabetes mellitus: mechanisms and clinical implications. Nat Rev Endocrinol. 2018;14(10):591–604. Find it ↗
- Leng F, Edison P. Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here? Nat Rev Neurol. 2021;17(3):157–172. Find it ↗
Educational content, not medical advice. If you have a health concern, speak to a qualified professional.