GFAP and S100B: What These Brain Support Cell Markers Mean

Written by Dr. Ryan Kneessi, ND

Quick answer: GFAP and S100B are proteins made mainly by the brain's support cells, called glial cells, and small amounts can be measured in the blood. Higher levels are generally read as a sign that these cells are activated or under strain, which research has linked with head injury, several neurological conditions and early brain changes with age. Neither marker points to a single cause, so results are read in context.

What can a blood test tell us about the brain’s support cells? Many of the cells in the brain are not neurons at all. Astrocytes and other glial cells hold the network together, help maintain the blood-brain barrier and respond when the brain is under strain. GFAP, short for glial fibrillary acidic protein, is a structural protein found in astrocytes, and S100B is a calcium-binding protein concentrated in glial cells. When these cells are activated or injured, small amounts of both proteins can show up in the blood, which is why researchers have studied them as windows into brain health.

This article is educational. It explains what the marker reflects and how researchers connect it to the deeper mechanisms of aging, so you can have a more informed conversation with your own provider.

What does a higher GFAP or S100B level mean?

A 2022 systematic review by Heimfarth and colleagues explained that when astrocytes break down, GFAP is released from brain tissue into the bloodstream. The review identified 48 studies covering 16 different neurological conditions, ranging from multiple sclerosis and Parkinson’s disease to seizures and depression, in which blood GFAP levels were associated with the condition being studied. That breadth is useful, but it also means a higher GFAP level points to strain on the brain’s support cells rather than to one specific cause.

S100B tells a similar story. In a 2012 review in the Journal of Neurochemistry, Michetti and colleagues described S100B as a protein concentrated in glial cells that is also found in some cell types outside the nervous system. Higher levels in body fluids have been linked with acute brain injury, perinatal brain distress, neurodegenerative and psychiatric conditions, yet levels also rise during stressful physical and mental activity. The clearest practical use so far comes from head injury research. In the ALERT-TBI study published in Lancet Neurology in 2018, Bazarian and colleagues tested 1,959 adults with suspected head injury and found that a blood test combining GFAP with a second protein, UCH-L1, had a sensitivity of 97.6 percent and a negative predictive value of 99.6 percent for injuries visible on a CT scan.

How are GFAP and S100B connected to aging and root causes?

Astrocyte activation is one way that chronic low-grade inflammation shows up inside the brain, and it is also a form of intercellular signaling, since astrocytes constantly talk with neurons and blood vessels. GFAP is now one of the most studied blood markers of brain aging. In the Swedish BioFINDER-2 study, published in Brain in 2021, Pereira and colleagues found that plasma GFAP was higher in every group of people with amyloid buildup in the brain, including people with normal thinking. GFAP tracked with amyloid even among cognitively normal people whose amyloid scans were still in the normal range, but not with tau once amyloid was taken into account, and higher GFAP was associated with cognitive decline over time. Because amyloid is a misfolded protein that clumps together, this connects GFAP to proteostasis, the way cells keep their proteins in good working order.

A 2021 study in Translational Psychiatry by Chatterjee and colleagues found that plasma GFAP was significantly higher in cognitively normal adults aged 65 to 90 who had a high brain amyloid load. On a much larger scale, Wang and colleagues analyzed 48,542 UK Biobank participants followed for about 13 years and found that GFAP and a related marker, neurofilament light, began rising up to 15 years before dementia was recognized, and that a faster yearly rise in GFAP was associated with faster cognitive decline. Genetic risk mattered too, since the number of APOE e4 gene copies correlated strongly with GFAP levels.

It is important to be honest that this research describes associations in groups of people. Links between these markers and other aging mechanisms, such as mitochondrial function or cellular senescence, are still early, and GFAP and S100B cannot predict what will happen to one person. From a root-cause perspective, the questions I find most useful are about what keeps the brain’s support cells on alert. Functional medicine looks at blood vessel and blood sugar health, sleep quality, physical activity, past head impacts, inflammation elsewhere in the body, gut health, nutrient status and everyday exposures, alongside genetics. These markers make the most sense when they are read together with that wider picture.

Can exercise or stress raise S100B?

Yes, and this is one of the main reasons a single result needs context. A 2014 review in Sports Medicine by Koh and Lee pulled together 23 studies that measured S100B after exercise. Fifteen of them, about 65 percent, reported a rise, although the increases were usually small. Exercise intensity and duration and any head impacts were the factors most likely to affect the result, while muscle breakdown, training level and oxidative stress were possible influences with weaker evidence. A recent hard workout, a contact sport or an unusually stressful period can therefore nudge S100B upward, so the circumstances around the blood draw matter.

What does the research show about GFAP and S100B?

The ALERT-TBI study enrolled 1,959 adults seen in emergency departments after a head injury who had a CT scan and a blood test within 12 hours. A combined GFAP and UCH-L1 blood test correctly flagged 97.6% of people with bleeding or injury on CT, and a negative test ruled out injury 99.6% of the time. Two-thirds of people tested positive, so the test was much better at ruling injury out than in. (Bazarian et al., 2018)

In the UK Biobank, blood GFAP was measured in 48,542 adults who were followed for about 13 years, during which 1,312 developed dementia. GFAP began rising up to 15 years before dementia was recognized, and higher GFAP was linked with roughly 2.3 to 3.2 times the risk. This was an observational study using a research assay, and the results do not yet translate to a clinical cutoff. (Wang et al., 2024)

Research on S100B in everyday settings is less consistent. Both markers are most established after head injury, and their use for brain aging is still being studied.

Related reading

If you would like to explore related topics, my articles on brain fog and memory, olive oil and brain aging and IL-6 and inflammation go deeper. You can also see the specialty tests I commonly recommend on my functional labs page.

Common questions about GFAP and S100B

Is a GFAP result a test for dementia?

No single GFAP result can say whether a person will develop dementia. Large studies link higher GFAP with brain amyloid buildup and later dementia across groups of people, but levels also rise with head injury and many other neurological conditions.

Why might S100B rise after a workout?

A review of 23 exercise studies found that about two thirds reported a rise in S100B after exercise, usually a small one, with intensity, duration and head impacts among the most likely factors.

What is the difference between GFAP and S100B?

GFAP is a structural protein found in astrocytes, while S100B is a calcium-binding protein concentrated in glial cells that is also found in some cell types outside the nervous system.

Sources

This article is for educational purposes only and is not medical advice. It does not replace an individual evaluation. Talk with your healthcare provider before making changes to your diet, exercise, supplements, or medications, especially if you are pregnant, nursing, or managing a health condition.