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.

Automated summary

Plasma GFAP can detect AD pathology in patients with MCI and predict conversion to AD dementia, showing potential clinical utility.