Plasma NfL and GFAP as biomarkers of spinal cord degeneration in adrenoleukodystrophy

Abstract

Objective: To explore the potential of neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) as biomarkers of spinal cord degeneration in adrenoleukodystrophy, as objective treatment-outcome parameters are needed. Methods: Plasma NfL and GFAP levels were measured in 45 male and 47 female ALD patients and compared to a reference cohort of 73 healthy controls. For male patients, cerebrospinal fluid (CSF) samples (n = 33) and 1-year (n = 39) and 2-year (n = 18) follow-up data were also collected. Severity of myelopathy was assessed with clinical parameters: Expanded Disability Status Scale (EDSS), Severity Scoring system for Progressive Myelopathy (SSPROM), and timed up-and-go. Results: NfL and GFAP levels were higher in male (P < 0.001, effect size (partial ƞ 2) NfL = 0.49, GFAP = 0.13) and female (P < 0.001, effect size NfL = 0.19, GFAP = 0.23) patients compared to controls; levels were higher in both symptomatic and asymptomatic patients. In male patients, NfL levels were associated with all three clinical parameters of severity of myelopathy (EDSS, SSPROM, and timed up-and go), while GFAP in male and NfL and GFAP in female patients were not. Changes in clinical parameters during follow-up did not correlate with (changes in) NfL or GFAP levels. Plasma and CSF NfL were strongly correlated (r = 0.60, P < 0.001), but plasma and CSF GFAP were not (r = 0.005, P = 0.98). Interpretation: Our study illustrates the potential of plasma NfL as biomarker of spinal cord degeneration in adrenoleukodystrophy, which was superior to plasma GFAP in our cohort.

Neurofilament light chain as a potential biomarker for monitoring neurodegeneration in X-linked adrenoleukodystrophy

“…However, the shortcomings of the EDSS rating must be pointed out 37 with future studies involving possibly more sensitive outcome measures like diffusion-weighted MRI of the cervical spinal cord and the corticospinal tracts in the brain 38 having the potential to further clarify this issue. During the revision of this manuscript, van Ballegoij and colleagues reported increased levels of NfL in both male and female AMN patients and found that in male patients, blood NfL was associated with clinical parameters of myelopathy as scored by EDSS, Severity Scoring system for Progressive Myelopathy (SSPROM) and timed up-and-go 39 . Accordingly, these investigations further support our observation that NfL may be of value also in the context of AMN.…”

Plasma glial fibrillary acidic protein detects Alzheimer pathology and predicts future conversion to Alzheimer dementia in patients with mild cognitive impairment

“…Glial fibrillary acidic protein (GFAP) is expressed in the cytoskeleton of astrocytes and has been found significantly increased in CSF in AD and other neurodegenerative diseases compared to healthy controls [12][13][14][15]. GFAP has also been recently measured in plasma and serum, where it was found increased in different neurological conditions, including AD [16][17][18][19][20][21][22][23][24]. Different studies have shown that higher concentrations of plasma GFAP were associated to amyloid-PET positivity and worse outcomes in global cognition [22,[24][25][26][27].…”

Plasma Glial Fibrillary Acidic Protein Detects Alzheimer Pathology and Predicts Future Conversion to Alzheimer Dementia in Patients With Mild Cognitive Impairment

“…Glial brillary acidic protein (GFAP) is expressed in the cytoskeleton of astrocytes and has been found signi cantly increased in CSF in AD and other neurodegenerative diseases compared to healthy controls (12)(13)(14)(15). GFAP has also been recently measured in plasma and serum, where it was found increased in different neurological conditions, including AD (16)(17)(18)(19)(20)(21)(22)(23)(24). Increase of plasma GFAP in AD patients was associated to amyloid-PET positivity and worse outcomes in global cognition (22,24,25).…”