Serum Neurofilament Light, Glial Fibrillary Acidic Protein and Tau Are Possible Serum Biomarkers for Activity of Brain Metastases and Gliomas

Abstract

BackgroundPrimary central nervous system (CNS) tumors and brain metastases (BMs) are major causes of morbidity and mortality, accompanied by low survival rates. Efforts to early discovery of CNS malignancies are critical. However, to date, there are no biomarkers approved for detection of cancer activity in the brain. Blood levels of neurofilament light (NfL) and tau, as well as glial fibrillary acidic protein (GFAp), show promise as biomarkers for brain injury in previous studies. Therefore, we performed a cross-sectional study to investigate correlations of those biomarkers with CNS activity of gliomas and BMs.MethodsSerum samples of 36 participants of a single centered institution were tested for NfL, GFAp and tau with Simoa immunoassay, and correlated with clinical and radiological data.ResultsNfL and GFAp levels were significantly associated with the state of intracranial disease (analysis of variance (ANOVA), PsNfL = 0.03; ANOVA, PGFAp = 0.03). Although statistically significant (P = 0.04), differences in concentrations were not clinically meaningful for tau levels. Serum NfL (sNfL) and GFAp concentrations were higher in the group of patients with CNS tumors with disease in progression versus CNS with stable disease (P = 0.03 and P = 0.01, respectively). In addition, sNfL were higher in patients with metastatic solid tumors with known BMs than in those with metastatic tumors with no BM (P = 0.0004).ConclusionsNfL and GFAp both apparently vary closely with presence and activity of gliomas and BMs. Further studies in larger populations are needed to expand these findings.

Neurofilament Light Chain as A Biomarker for Brain Metastases

“…Hence, a release of NfL would be expected as a consequence of the neuronal damage caused by the infiltration of the brain metastasis in the brain parenchyma [ 18 ] and/or brain compression caused by the metastasis. In line with this, a recent study found elevated NfL levels in seven cancer patients with brain metastasis compared with healthy controls [ 19 ], which supports our findings.…”

Evaluation of plasma tau and neurofilament light chain biomarkers in a 12-year clinical cohort of human prion diseases

“…If an experimental therapeutic agent affected these other processes, it may change biomarker levels independently of any effect on neurodegeneration. Plasma tau and NfL have some appealing and complementary properties as therapeutic markers, and notably different half-lives in blood 30 , but their suitability should be evaluated directly in patients receiving putative treatments. It would also be useful to study them in animal models in which successful treatment of prion disease can be achieved 11 .…”

Evaluation of Serum Neurofilament Light Chain and Glial Fibrillary Acidic Protein as Screening and Monitoring Biomarkers for Brain Metastases

“…The upregulation of GFAP following reactive astrogliosis and destruction of astrocyte structural integrity combined with blood–brain barrier disruption may lead to increased sGFAP levels in patients with BMs [ 26 , 27 ]. Although an increasing number of studies reported the roles of sNFL and sGFAP in various neurological disorders, data are scarce for patients with BMs [ 28 , 29 ]. Hepner et al showed higher concentrations of sNfL and sGFAP in 22 patients with gliomas or BMs compared to those in nine patients without BMs [ 28 ].…”

“…Although an increasing number of studies reported the roles of sNFL and sGFAP in various neurological disorders, data are scarce for patients with BMs [ 28 , 29 ]. Hepner et al showed higher concentrations of sNfL and sGFAP in 22 patients with gliomas or BMs compared to those in nine patients without BMs [ 28 ]. Another recent study showed higher sNfL levels in 43 patients with BMs compared to those observed in 25 without BMs, although there was no age-matching in the comparison [ 29 ].…”