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

Introduction Plasma glial fibrillary acidic protein (GFAP) is a marker of astroglial activation and astrocytosis. We assessed the ability of plasma GFAP to detect Alzheimer's disease (AD) pathology in the form of AD-related amyloid-beta (A beta) pathology and conversion to AD dementia in a mild cognitive impairment (MCI) cohort. Method One hundred sixty MCI patients were followed for 4.7 years (average). AD pathology was defined using cerebrospinal fluid (CSF) A beta 42/40 and A beta 42/total tau (T-tau). Plasma GFAP was measured at baseline and follow-up using Simoa technology. Results Baseline plasma GFAP could detect abnormal CSF A beta 42/40 and CSF A beta 42/T-tau with an AUC of 0.79 (95% CI 0.72-0.86) and 0.80 (95% CI 0.72-0.86), respectively. When also including APOE epsilon 4 status as a predictor, the accuracy of the model to detect abnormal CSF A beta 42/40 status improved (AUC = 0.86, p = 0.02). Plasma GFAP predicted subsequent conversion to AD dementia with an AUC of 0.84 (95% CI 0.77-0.91), which was not significantly improved when adding APOE epsilon 4 or age as predictors to the model. Longitudinal GFAP slopes for A beta-positive and MCI who progressed to dementia (AD or other) were significantly steeper than those for A beta-negative (p = 0.007) and stable MCI (p < 0.0001), respectively. Conclusion Plasma GFAP can detect AD pathology in patients with MCI and predict conversion to AD dementia.