Blood GFAP may be biomarker of brain shrinkage in AQP4-NMOSD
Study: Association not seen in patients with MOGAD, a related condition
Higher blood levels of the glial fibrillary acidic protein (GFAP) are significantly associated with shrinkage in certain brain regions of people with neuromyelitis optica spectrum disorder (NMOSD) who have antibodies against the AQP4 protein, a study showed.
This association was not observed in people with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), a related condition, further emphasizing the association between GFAP and brain shrinkage in AQP4-related NMOSD.
The specific associations of [blood GFAP]with brain MRI volumes corroborate [it] as a biomarker for disease activity in [AQP4-related NMOSD],” researchers wrote.
The study, “Investigation of the association of serum GFAP and NfL with brain and upper cervical MRI volumes in AQP4-IgG-positive NMOSD and MOGAD,” was published in Therapeutic Advances in Neurological Disorders.
Six patients experienced NMOSD attack during 1-year follow-up period
NMOSD is an inflammatory disorder that causes damage mainly in the spinal cord and optic nerves, which relay signals between the eyes and the brain. Most cases are associated with the production of self-reactive antibodies that target AQP4, a protein found at the surface of nerve-supporting cells called astrocytes.
Previous studies suggest that blood levels of GFAP, a protein abundant in astrocytes, may be a blood marker of disability and disease activity that could predict relapse risk in NMOSD patients with anti-AQP4 antibodies.
However, “it remains unclear whether structural damage detected by MRI in patients with [AQP4-related NMOSD] may be reflected by [blood GFAP levels],” the researchers wrote.
To learn more, researchers retrospectively analyzed blood and MRI data from 33 adults with AQP4-related NMOSD, 17 adults with MOGAD, and 15 healthy adults. All NMOSD and MOGAD patients were in clinical remission, defined by more than 30 days since the onset of the last attack at the time of the study’s visits.
NMOSD patients’ median age was 50 years, and 90.9% were women. Their median disease duration was 76 months, or about six years. Most (87.9%) were on immunotherapy. Six patients experienced an NMOSD attack during a one-year follow-up period.
The NMOSD group was generally older and more often female than the other two groups, and disability was worse among people with NMOSD than those with MOGAD.
NMOSD patients had higher blood GFAP levels than healthy controls
Participants with NMOSD had significantly higher blood GFAP levels than healthy controls, and a trend toward high levels compared with MOGAD patients.
The team also looked at blood levels of neurofilament light chain (NfL), a marker of nerve injury.
At first assessment, NMOSD patients had significantly lower volumes of the brain, gray matter (mainly consisting of nerve cell bodies), and globus pallidus, a brain region involved in regulating voluntary movements, relative to healthy controls.
Those with NMOSD also had a significantly smaller amygdala, a brain structure involved in processing emotions, than those with MOGAD. The NMOSD group also had a reduced upper cervical spinal cord area and more brain lesions compared with the other two groups.
Statistical analyses adjusted for sex and age showed that in NMOSD participants, higher blood GFAP levels were significantly associated with a lower volume of several brain regions, including the hippocampus and thalamus, and a higher volume of cerebrospinal fluid, the liquid that bathes the brain and spinal cord, in the brain.
The hippocampus is involved in memory, learning, and spatial navigation, while the thalamus is a major relay station for sensory and motor signals.
“Cognitive impairment, which is a frequent symptom in [AQP4-related NMOSD], has previously been linked to gray matter, thalamic, and hippocampal volume loss,” the researchers wrote.
[These findings] “corroborate [GFAP] as a [disease-related] biomarker of [AQP4-related NMOSD] and are compatible with the concept of subclinical disease activity.
The observed links between blood GFAP levels and structural brain measures in NMOSD were either less pronounced or absent in MOGAD patients and healthy controls.
“The selective association of reduced volumes of the thalami and hippocampi, but not other deep gray matter structures, with higher [blood GFAP] in patients with [AQP4-related NMOSD] is likely to represent a disease-specific phenomenon,” the researchers wrote.
Still, the fact that these links were observed in clinically stable patients “implies either (a) that both persistent [astrocyte damage] and volume loss are sequelae of previous disease activity, that is acute attacks, or (b) that they are related to ongoing subclinical disease activity,” they added.
Higher blood NfL levels were significantly associated with low hippocampal volume in the NMOSD group, but not in the other groups. No other significant links were observed.
The team also found that higher GFAP levels were associated with a higher lesion volume in NMOSD participants. No relevant associations were detected in the other groups.
“We conducted the first systematic evaluation of the association of [blood GFAP], [blood NfL], and advanced MRI measures in patients with [AQP4-related NMOSD],” the team wrote. These findings “corroborate [GFAP] as a [disease-related] biomarker of [AQP4-related NMOSD] and are compatible with the concept of subclinical disease activity.”
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