Plasma neurofilament light chain and glial fibrillary acidic protein predict stroke in CADASIL

Abstract

Background: Stroke remains the most cumbersome disease burden in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). This study aimed to investigate whether plasma biomarkers can reflect disease severity and predict stroke recurrence in CADASIL patients. Methods: Sixty-three CADASIL patients (mean age 58.9 ± 9.3 years old, male 63%) from a multicenter registry and 17 controls were recruited. Plasma biomarkers, namely neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), tau, and ubiquitin carboxy-terminal hydrolase L1 (UCHL1), were measured using an ultra-sensitive single molecule array at baseline. Neuroimaging markers assessed included the Fazekas scale of white matter hyperintensity, numbers of lacunes, and cerebral microbleeds (CMBs). Cox proportional hazards regression models were applied to calculate the hazard ratio (HR) of plasma biomarkers at baseline for predicting incident stroke during follow-up. Results: Plasma NfL, GFAP, and UCHL1 levels were significantly elevated in the CADASIL patients than in the controls. Among the CADASIL patients, both plasma NfL and GFAP levels positively correlated with the numbers of CMBs (r = 0.32 and r = 0.37, respectively; both p < 0.05). Higher plasma levels of NfL and GFAP were associated with any stroke (odds ratio 2.02, 95% confidence interval [CI] 1.06-3.87) and ICH (odds ratio 2.06, 95% CI 1.26-3.35) at baseline, respectively. Within a mean follow-up period of 3.1 ± 2.1 years, 10 patients (16%) had incident stroke and 6 of them were ICH. Higher baseline NfL (HR 1.93, 95% CI 1.19-3.13) predicted any incident stroke, whereas higher GFAP (HR 2.80, 95% CI 1.21-6.53) predicted incident ICH. Conclusions: In CADASIL patients, plasma NfL can be a promising biomarker for monitoring incident stroke, whereas GFAP may have a role in cerebral hemorrhage.

Plasma neurofilament light chain level predicts outcomes in stroke patients receiving endovascular thrombectomy

“…Second, even in a prospective registration setting, some factors for which adjustments were necessary in the multivariable analysis may not have been adjusted. Third, we did not determine a clear cutoff value for the biomarkers for predicting outcomes, unlike several relevant studies [ 10 , 13 , 17 ]. However, variations among stroke centers in terms of patient profiles, acute treatment strategies, and standard care protocols may complicate the acquisition of a universally applicable set of values for predicting outcomes.…”

“…For example, a panel of single-molecule arrays focused on the CNS can simultaneously measure the levels of several biomarkers, including neurofilament light chain (NfL), glial fibrillary astrocytic protein (GFAP), tau, and ubiquitin C-terminal hydrolase L1 (UCHL1) [ 9 , 10 ]. NfL is a neuronal scaffolding protein, and its levels in cerebrospinal fluid and plasma are elevated in individuals with neurological disorders, including acute stroke [ 11 ].…”

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).…”