Association of plasma GFAP with elevated brain amyloid is dependent on severity of white matter lesions in an Asian cognitively impaired cohort

Abstract INTRODUCTION While elevated blood glial fibrillary acidic protein (GFAP) has been associated with brain amyloid pathology, whether this association occurs in populations with high cerebral small vessel disease (CSVD) concomitance remains unclear. METHODS Using a Singapore‐based cohort of cognitively impaired subjects, we assessed associations between plasma GFAP and neuroimaging measures of brain amyloid and CSVD, including white matter hyperintensities (WMH). We also examined the diagnostic performance of plasma GFAP in detecting brain amyloid beta positivity (Aβ+). RESULTS When stratified by WMH status, elevated brain amyloid was associated with higher plasma GFAP only in the WMH– group (β = 0.383; P < 0.001). The diagnostic performance of plasma GFAP in identifying Aβ+ was significantly higher in the WMH– group (area under the curve [AUC] = 0.896) than in the WMH+ group (AUC = 0.712, P = 0.008). DISCUSSION The biomarker utility of plasma GFAP in detecting brain amyloid pathology is dependent on the severity of concomitant WMH. Highlight Glial fibrillary acidic protein (GFAP)’s association with brain amyloid is unclear in populations with high cerebral small vessel disease (CSVD). Plasma GFAP was measured in a cohort with CSVD and brain amyloid. Plasma GFAP was better in detecting amyloid in patients with low CSVD versus high CSVD. Biomarker utility of GFAP in detecting brain amyloid depends on the severity of CSVD.