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GFAP as a biomarker for neurological disease is it a pile of?

Posted on September 4, 2025 by s3GvGjerAz
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GFAP is glial acidic fibrillary acidic protein and is a marker of astrocytes. Neurofilament is a marker in nerves and in MS these proteins are released. I have associated these with nerve damage and there has been a great move to suggest that the release of GFAP is a marker of astrocyte activation and it is suggested it is a marker of progression…I am not sure I completely buy this as we showed that there is an increase in EAE about thirty years ago and this was associated with inflammatory attack but now this report. It seems the bosses are torturing their staff and making them sift through SH1 to look for GFAP….Looking in spinal fluid to look at brain disease is one thing, looking in the blood is another but in this study they look in the SH1 of people with MS and here they suggest that the GFAP maybe coming from the glial cells in the gut. These cells will be close to vessels and so I have to now ask is the serum level due to brain function or gut function. The correlations to any outcome are not great and now it makes me wonder what it means. When you get a lesion you get astrocyte activation and when you get demyelination you get astrocyte activation.

Schwerdtfeger LA, Montini F, Antonini Cencicchio M, Christenson JR, Glanz BI, Falcone M, Filippi M, Cox LM, Chitnis T, Weiner HL. Stool Glial Fibrillary Acidic Protein Is Elevated in Progressive Multiple Sclerosis. Neurol Neuroimmunol Neuroinflamm. 2025 Nov;12(6):e200466. doi: 10.1212/NXI.0000000000200466. 

Objectives: The gut microbiota and altered intestinal physiology have been implicated in multiple sclerosis (MS). Enteric glial cells regulate enteric nervous and immune function and express glial fibrillary acidic protein (GFAP) and S100β. Serum GFAP and neurofilament light chain can predict disease worsening; however, no clear markers differentiate relapsing from progressive disease.

Methods: To investigate enteric glial function in MS, we measured stool GFAP (st-GFAP) using an enzyme-linked immunosorbent assay in 31 healthy controls (HCs), 77 patients with relapsing remitting MS (RRMS), and 53 patients with progressive MS (ProgMS). Participants underwent clinical follow-up at 2 and 5 years after stool donation.

Results: We found higher st-GFAP levels in patients with ProgMS compared with those with RRMS and HCs. St-GFAP was positively correlated with baseline Expanded Disability Status Scale (EDSS) score, 25-foot walk time, and an increased EDSS score at 2 and 5 years. We found enteric glial hyperplasia in the colonic mucosa of a patient with primary progressive MS, as indicated by GFAP and S100β immunoreactivity, an effect not observed in duodenum tissue in patients with RRMS from our Milan cohort. St-GFAP in patients with ProgMS was negatively associated with Eubacterium hallii.

Discussion: These exploratory data indicate an altered enteric glial phenotype in patients with ProgMS and suggest that st-GFAP may be a prognostic biomarker.

Source: multiple-sclerosis-research.org

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