Glial Fibrillary Acidic Protein (GFAP), Plasma

Glial Fibrillary Acidic Protein (GFAP), Plasma

This test is used to assess the inflammatory response and damage in the central nervous system.

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Glial Fibrillary Acidic Protein (GFAP), Plasma

Test Summary

 

Glial Fibrillary Acidic Protein (GFAP), Plasma

Test code: 14319

 

Clinical use

  • Assess response to injury in neurological disorders
  • Assess Alzheimer's disease (AD) staging and progression and monitor anti-amyloid therapy treatment response

Clinical background

Glial fibrillary acidic protein (GFAP) is an intermediate filament protein predominantly expressed in the astrocytes in the central nervous system (CNS). In response to CNS damage, quiescent astrocytes undergo changes in morphology and function (astrogliosis) and upregulate GFAP expression to repair damage, which causes glial scars. Drainage of GFAP into the bloodstream enables less invasive measurement of astrocytic response to many neurological conditions.1

GFAP has been studied as a blood-based biomarker for a range of neurological conditions (Table).2–13 The dynamics of blood GFAP levels depend on the nature of the associated neurological conditions. In acute conditions, such as traumatic brain injury (TBI) or intracerebral hemorrhage, blood GFAP levels peak and decline promptly.14 In contrast, in neurodegenerative and neuroinflammatory diseases, elevated blood GFAP levels persist and reflect ongoing or accumulating astrogliosis.2 For example, GFAP is considered one of the markers of nonspecific processes involved in AD pathophysiology.15

Table. Potential Clinical Use of Blood GFAP Level in Neurological Conditions

Neurological condition

Clinical findings and associated GFAP blood level responsesa

Potential clinical use

Neurodegenerative

AD
  • Elevated in asymptomatic and symptomatic stages of AD3 
  • Higher levels associated with more advanced disease stages4 
  • Decreased in patients with anti-amyloid therapies5 
  • Predict cognitive decline and clinical progression to AD dementia3 
  • Assess disease state4 
  • Monitor anti-amyloid treatment5 

FTD
  • Higher in symptomatic patients with GRN mutations than symptomatic patients with other mutations associated with FTD6 
  • Elevations associated with symptom appearance in GRN mutation carriers6
  • Predict symptom onset in patients with GRN mutation6 

Inflammatory

MS
  • Higher in progressive MS than in non-inflammatory neurological diseases or relapsing-remitting MS7 
  • Elevations correlate with the severity of disability2 
  • Assess disease stage and progression7 

NMOSD
  • High baseline levels associated with risk of relapse8 
  • Higher in NMOSD than in MS2 
  • Identify patients with high relapse risk8 

 

Acute CNS injury

TBI
  • Elevations correlate with the severity of intracranial pathology9 
  • Screen patients with mild TBI for intracranial abnormalities10 

TSCI
  • Elevations associated with the presence and severity of the injury2 
  • Determine severity and predict outcome2 

CVAs
  • Higher in intracerebral hemorrhage than in acute ischemic stroke11 
  • Higher in large lobar hemorrhage than in deep intracerebral hemorrhage11 
  • Differentiate intracerebral hemorrhage from acute ischemic stroke with similar symptoms12 

Brain tumors

GBM
  • Higher in GBM than in other nonglial primary tumors or brain metastasis2 
  • Levels correlate with preoperative tumor volume and necrotic volume2 
  • Identify GBM tumor type in patients with newly diagnosed brain tumor13 
AD, Alzheimer's disease; CNS, central nervous system; CVAs, cerebrovascular accidents; FTD, frontotemporal dementia; GBM, glioblastoma multiforme; GFAP; glial fibrillary acidic protein; MS, multiple sclerosis; NMOSD, neuromyelitis optica spectrum disorder; TBI, traumatic brain injury; TSCI, traumatic spinal cord injury.
a Blood GFAP levels vary among different methods and platforms; results obtained in different studies may not be comparable.2

 

Quest Diagnostics offers the Glial Fibrillary Acidic Protein (GFAP), Plasma (test code 14319) test to determine blood GFAP concentration as a less invasive tool (compared to cerebrospinal fluid analysis) to inform clinical decisions on neurological conditions.

Individuals suitable for testing

  • Individuals with conditions that involve CNS damage or neuroinflammation

Method

  • Electrochemiluminescence immunoassay (ECLIA)
  • Analytical sensitivity: 10.0 pg/mL
  • Analytical measurement range: 10.0-25,000.0 pg/mL

Interpretive information

Elevated levels of plasma GFAP indicate active astrogliosis in the CNS.2 

Normal levels of plasma GFAP indicate that the suspected condition does not involve active astrogliosis.2 

Levels are compared with age-specific reference ranges for healthy populations because expression of GFAP increases with age in healthy individuals.16 

In older individuals with neurodegenerative diseases, mixed brain pathologies often coexist. The involvement of GFAP in a range of neurological and systemic conditions can complicate interpretation of results.2 

In addition to GFAP being expressed by astrocytes in the CNS, small amounts of GFAP are expressed in the periphery in neural or non-neural cells, such as Schwann cells, chondrocytes, and hepatic stella cells.1 

References

  1. Middeldorp J, Hol EM. GFAP in health and disease. Prog Neurobiol. 2011;93(3):421-443. doi:10.1016/j.pneurobio.2011.01.005
  2. Abdelhak A, Foschi M, Abu-Rumeileh S, et al. Blood GFAP as an emerging biomarker in brain and spinal cord disorders. Nat Rev Neurol. 2022;18(3):158-172. doi:10.1038/s41582-021-00616-3
  3. Heneka MT, Gauthier S, Chandekar SA, et al. Neuroinflammatory fluid biomarkers in patients with Alzheimer’s disease: a systematic literature review. Mol Psychiatry. Published online March 6, 2025. doi:10.1038/s41380-025-02939-9
  4. Holper S, Loveland P, Churilov L, et al. Blood astrocyte biomarkers in Alzheimer disease. Neurology. 2024;103(3):e209537. doi:10.1212/wnl.0000000000209537
  5. Hu Y, Cho M, Sachdev P, et al. Fluid biomarkers in the context of amyloid-targeting disease-modifying treatments in Alzheimer’s disease. Med. 2024;5(10):1206-1226. doi:10.1016/j.medj.2024.08.004
  6. Heller C, Foiani MS, Moore K, et al. Plasma glial fibrillary acidic protein is raised in progranulin-associated frontotemporal dementia. J Neurol, Neurosurg Psychiatry. 2020;91(3):263-270. doi:10.1136/jnnp-2019-321954
  7. Abdelhak A, Huss A, Kassubek J, et al. Serum GFAP as a biomarker for disease severity in multiple sclerosis. Sci Rep. 2018;8(1):14798. doi:10.1038/s41598-018-33158-8
  8. Aktas O, Smith MA, Rees WA, et al. Serum glial fibrillary acidic protein: a neuromyelitis optica spectrum disorder biomarker. Ann Neurol. 2021;89(5):895-910. doi:10.1002/ana.26067
  9. Czeiter E, Amrein K, Gravesteijn BY, et al. Blood biomarkers on admission in acute traumatic brain injury: Relations to severity, CT findings and care path in the CENTER-TBI study. EBioMedicine. 2020;56:102785. doi:10.1016/j.ebiom.2020.102785
  10. Karamian A, Farzaneh H, Khoshnoodi M, et al. Accuracy of GFAP and UCH-L1 in predicting brain abnormalities on CT scans after mild traumatic brain injury: a systematic review and meta-analysis. Eur J Trauma Emerg Surg. 2025;51(1):68. doi:10.1007/s00068-024-02697-3
  11. Luger S, Witsch J, Dietz A, et al. Glial fibrillary acidic protein serum levels distinguish between intracerebral hemorrhage and cerebral ischemia in the early phase of stroke. Clin Chem. 2017;63(1):377-385. doi:10.1373/clinchem.2016.263335
  12. Perry LA, Lucarelli T, Penny-Dimri JC, et al. Glial fibrillary acidic protein for the early diagnosis of intracerebral hemorrhage: systematic review and meta-analysis of diagnostic test accuracy. Int J Stroke. 2018;14(4):390-399. doi:10.1177/1747493018806167
  13. Tichy J, Spechtmeyer S, Mittelbronn M, et al. Prospective evaluation of serum glial fibrillary acidic protein (GFAP) as a diagnostic marker for glioblastoma. J Neuro-Oncol. 2016;126(2):361-369. doi:10.1007/s11060-015-1978-8
  14. Papa L, Brophy GM, Welch RD, et al. Time course and diagnostic accuracy of glial and neuronal blood biomarkers GFAP and UCH-L1 in a large cohort of trauma patients with and without mild traumatic brain injury. JAMA Neurol. 2016;73(5):551. doi:10.1001/jamaneurol.2016.0039
  15. Jack CR, Andrews JS, Beach TG, et al. Revised criteria for diagnosis and staging of Alzheimer’s disease: Alzheimer’s Association Workgroup. Alzheimers Dement. 2024;20(8):5143-5169. doi:10.1002/alz.13859
  16. Nichols NR, Day JR, Laping NJ, et al. GFAP mRNA increases with age in rat and human brain. Neurobiol Aging. 1993;14(5):421-429. doi:10.1016/0197-4580(93)90100-p
     

Content reviewed 04/2025

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This test is used to assess the inflammatory response and damage in the central nervous system.

Test Guide List

Glial Fibrillary Acidic Protein (GFAP), Plasma

Test Summary

 

Glial Fibrillary Acidic Protein (GFAP), Plasma

Test code: 14319

 

Clinical use

  • Assess response to injury in neurological disorders
  • Assess Alzheimer's disease (AD) staging and progression and monitor anti-amyloid therapy treatment response

Clinical background

Glial fibrillary acidic protein (GFAP) is an intermediate filament protein predominantly expressed in the astrocytes in the central nervous system (CNS). In response to CNS damage, quiescent astrocytes undergo changes in morphology and function (astrogliosis) and upregulate GFAP expression to repair damage, which causes glial scars. Drainage of GFAP into the bloodstream enables less invasive measurement of astrocytic response to many neurological conditions.1

GFAP has been studied as a blood-based biomarker for a range of neurological conditions (Table).2–13 The dynamics of blood GFAP levels depend on the nature of the associated neurological conditions. In acute conditions, such as traumatic brain injury (TBI) or intracerebral hemorrhage, blood GFAP levels peak and decline promptly.14 In contrast, in neurodegenerative and neuroinflammatory diseases, elevated blood GFAP levels persist and reflect ongoing or accumulating astrogliosis.2 For example, GFAP is considered one of the markers of nonspecific processes involved in AD pathophysiology.15

Table. Potential Clinical Use of Blood GFAP Level in Neurological Conditions

Neurological condition

Clinical findings and associated GFAP blood level responsesa

Potential clinical use

Neurodegenerative

AD
  • Elevated in asymptomatic and symptomatic stages of AD3 
  • Higher levels associated with more advanced disease stages4 
  • Decreased in patients with anti-amyloid therapies5 
  • Predict cognitive decline and clinical progression to AD dementia3 
  • Assess disease state4 
  • Monitor anti-amyloid treatment5 

FTD
  • Higher in symptomatic patients with GRN mutations than symptomatic patients with other mutations associated with FTD6 
  • Elevations associated with symptom appearance in GRN mutation carriers6
  • Predict symptom onset in patients with GRN mutation6 

Inflammatory

MS
  • Higher in progressive MS than in non-inflammatory neurological diseases or relapsing-remitting MS7 
  • Elevations correlate with the severity of disability2 
  • Assess disease stage and progression7 

NMOSD
  • High baseline levels associated with risk of relapse8 
  • Higher in NMOSD than in MS2 
  • Identify patients with high relapse risk8 

 

Acute CNS injury

TBI
  • Elevations correlate with the severity of intracranial pathology9 
  • Screen patients with mild TBI for intracranial abnormalities10 

TSCI
  • Elevations associated with the presence and severity of the injury2 
  • Determine severity and predict outcome2 

CVAs
  • Higher in intracerebral hemorrhage than in acute ischemic stroke11 
  • Higher in large lobar hemorrhage than in deep intracerebral hemorrhage11 
  • Differentiate intracerebral hemorrhage from acute ischemic stroke with similar symptoms12 

Brain tumors

GBM
  • Higher in GBM than in other nonglial primary tumors or brain metastasis2 
  • Levels correlate with preoperative tumor volume and necrotic volume2 
  • Identify GBM tumor type in patients with newly diagnosed brain tumor13 
AD, Alzheimer's disease; CNS, central nervous system; CVAs, cerebrovascular accidents; FTD, frontotemporal dementia; GBM, glioblastoma multiforme; GFAP; glial fibrillary acidic protein; MS, multiple sclerosis; NMOSD, neuromyelitis optica spectrum disorder; TBI, traumatic brain injury; TSCI, traumatic spinal cord injury.
a Blood GFAP levels vary among different methods and platforms; results obtained in different studies may not be comparable.2

 

Quest Diagnostics offers the Glial Fibrillary Acidic Protein (GFAP), Plasma (test code 14319) test to determine blood GFAP concentration as a less invasive tool (compared to cerebrospinal fluid analysis) to inform clinical decisions on neurological conditions.

Individuals suitable for testing

  • Individuals with conditions that involve CNS damage or neuroinflammation

Method

  • Electrochemiluminescence immunoassay (ECLIA)
  • Analytical sensitivity: 10.0 pg/mL
  • Analytical measurement range: 10.0-25,000.0 pg/mL

Interpretive information

Elevated levels of plasma GFAP indicate active astrogliosis in the CNS.2 

Normal levels of plasma GFAP indicate that the suspected condition does not involve active astrogliosis.2 

Levels are compared with age-specific reference ranges for healthy populations because expression of GFAP increases with age in healthy individuals.16 

In older individuals with neurodegenerative diseases, mixed brain pathologies often coexist. The involvement of GFAP in a range of neurological and systemic conditions can complicate interpretation of results.2 

In addition to GFAP being expressed by astrocytes in the CNS, small amounts of GFAP are expressed in the periphery in neural or non-neural cells, such as Schwann cells, chondrocytes, and hepatic stella cells.1 

References

  1. Middeldorp J, Hol EM. GFAP in health and disease. Prog Neurobiol. 2011;93(3):421-443. doi:10.1016/j.pneurobio.2011.01.005
  2. Abdelhak A, Foschi M, Abu-Rumeileh S, et al. Blood GFAP as an emerging biomarker in brain and spinal cord disorders. Nat Rev Neurol. 2022;18(3):158-172. doi:10.1038/s41582-021-00616-3
  3. Heneka MT, Gauthier S, Chandekar SA, et al. Neuroinflammatory fluid biomarkers in patients with Alzheimer’s disease: a systematic literature review. Mol Psychiatry. Published online March 6, 2025. doi:10.1038/s41380-025-02939-9
  4. Holper S, Loveland P, Churilov L, et al. Blood astrocyte biomarkers in Alzheimer disease. Neurology. 2024;103(3):e209537. doi:10.1212/wnl.0000000000209537
  5. Hu Y, Cho M, Sachdev P, et al. Fluid biomarkers in the context of amyloid-targeting disease-modifying treatments in Alzheimer’s disease. Med. 2024;5(10):1206-1226. doi:10.1016/j.medj.2024.08.004
  6. Heller C, Foiani MS, Moore K, et al. Plasma glial fibrillary acidic protein is raised in progranulin-associated frontotemporal dementia. J Neurol, Neurosurg Psychiatry. 2020;91(3):263-270. doi:10.1136/jnnp-2019-321954
  7. Abdelhak A, Huss A, Kassubek J, et al. Serum GFAP as a biomarker for disease severity in multiple sclerosis. Sci Rep. 2018;8(1):14798. doi:10.1038/s41598-018-33158-8
  8. Aktas O, Smith MA, Rees WA, et al. Serum glial fibrillary acidic protein: a neuromyelitis optica spectrum disorder biomarker. Ann Neurol. 2021;89(5):895-910. doi:10.1002/ana.26067
  9. Czeiter E, Amrein K, Gravesteijn BY, et al. Blood biomarkers on admission in acute traumatic brain injury: Relations to severity, CT findings and care path in the CENTER-TBI study. EBioMedicine. 2020;56:102785. doi:10.1016/j.ebiom.2020.102785
  10. Karamian A, Farzaneh H, Khoshnoodi M, et al. Accuracy of GFAP and UCH-L1 in predicting brain abnormalities on CT scans after mild traumatic brain injury: a systematic review and meta-analysis. Eur J Trauma Emerg Surg. 2025;51(1):68. doi:10.1007/s00068-024-02697-3
  11. Luger S, Witsch J, Dietz A, et al. Glial fibrillary acidic protein serum levels distinguish between intracerebral hemorrhage and cerebral ischemia in the early phase of stroke. Clin Chem. 2017;63(1):377-385. doi:10.1373/clinchem.2016.263335
  12. Perry LA, Lucarelli T, Penny-Dimri JC, et al. Glial fibrillary acidic protein for the early diagnosis of intracerebral hemorrhage: systematic review and meta-analysis of diagnostic test accuracy. Int J Stroke. 2018;14(4):390-399. doi:10.1177/1747493018806167
  13. Tichy J, Spechtmeyer S, Mittelbronn M, et al. Prospective evaluation of serum glial fibrillary acidic protein (GFAP) as a diagnostic marker for glioblastoma. J Neuro-Oncol. 2016;126(2):361-369. doi:10.1007/s11060-015-1978-8
  14. Papa L, Brophy GM, Welch RD, et al. Time course and diagnostic accuracy of glial and neuronal blood biomarkers GFAP and UCH-L1 in a large cohort of trauma patients with and without mild traumatic brain injury. JAMA Neurol. 2016;73(5):551. doi:10.1001/jamaneurol.2016.0039
  15. Jack CR, Andrews JS, Beach TG, et al. Revised criteria for diagnosis and staging of Alzheimer’s disease: Alzheimer’s Association Workgroup. Alzheimers Dement. 2024;20(8):5143-5169. doi:10.1002/alz.13859
  16. Nichols NR, Day JR, Laping NJ, et al. GFAP mRNA increases with age in rat and human brain. Neurobiol Aging. 1993;14(5):421-429. doi:10.1016/0197-4580(93)90100-p
     

Content reviewed 04/2025

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Reference ranges are provided as general guidance only. To interpret test results use the reference range in the laboratory report.

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