Recent studies reported increased plasma glial acidic fibrillary
protein (GFAP) levels in
amyotrophic lateral sclerosis (ALS) patients compared to controls. We expanded these findings in a larger cohort, including 156 ALS patients and 48 controls, and investigated the associations of plasma GFAP with clinical variables and other biofluid
biomarkers. Plasma GFAP and
Alzheimer's disease (AD) cerebrospinal fluid (CSF)
biomarkers were assessed by the single molecule array and the Lumipulse platforms, respectively. In ALS patients, plasma GFAP was higher than in controls (p < 0.001) and associated with measures of
cognitive decline. Twenty ALS patients (12.8%) showed a positive
amyloid status (A+), of which nine also exhibited tau pathology (A+T+, namely ALS-AD). ALS-AD patients showed higher plasma GFAP than A- ALS participants (p < 0.001) and controls (p < 0.001), whereas the comparison between A- ALS and controls missed statistical significance (p = 0.07). Plasma GFAP distinguished ALS-AD subjects more accurately (area under the curve (AUC) 0.932 ± 0.027) than plasma p-tau181 (AUC 0.692 ± 0.058, p < 0.0001) and plasma neurofilament light chain
protein (AUC, 0.548 ± 0.088, p < 0.0001). Cognitive measures differed between ALS-AD and other ALS patients. AD co-pathology deeply affects plasma GFAP values in ALS patients. Plasma GFAP is an accurate
biomarker for identifying AD co-pathology in ALS, which can influence the cognitive phenotype.