Claudia Cicognola, Sweden
Lund University Clinical Memory Research UnitPresenter of 2 Presentations
PLASMA GLIAL FIBRILLARY ACIDIC PROTEIN PREDICTS AMYLOID STATUS AND FUTURE CONVERSION TO ALZHEIMER’S DISEASE IN A MILD COGNITIVE IMPAIRMENT LONGITUDINAL COHORT
Abstract
Aims
Astrogliosis in response to amyloid-beta (Aβ) plaques is an early feature of Alzheimer's disease (AD). Glial fibrillary acidic protein (GFAP) is expressed in astrocytes and is increased in CSF in AD. Studies on plasma GFAP as AD biomarker are few and not longitudinal. Our aim was to evaluate plasma GFAP as potential biomarker for Aβ status and for future development of AD dementia.
Methods
161 subjects with a baseline clinical diagnosis of mild cognitive impairment (MCI) were included, genotyped for APOE, followed for 4.7 years (average) and assessed for conversion to AD at follow-up. Plasma was collected at baseline and follow-up. GFAP was measured with Simoa GFAP Discovery kit for SR-X (Quanterix). Aß positivity (Aß+) was defined as CSF Aβ42/40 <0.07 (cut-off calculated with Youden index within the cohort).
Results
Baseline GFAP was increased in Aβ+ MCI patients (p<0.0001). Plasma GFAP could predict Aβ+ status (p<0.0001, AIC=184.3, AUC=0.787, sensitivity=73%, specificity=75%). Accuracy was increased by combining plasma GFAP and APOE genotype (p<0.0001, AIC 154.7, AUC=0.859). Plasma GFAP could also predict subsequent development of AD dementia (p<0.0001, AIC=154.4, AUC=0.836, sensitivity=72%, specificity=85%). Predictive accuracy of future AD dementia was improved by combining plasma GFAP with APOE genotype and age (p<0.0001, AIC=140, AUC=0.864). Longitudinal slopes showed a significant increase of plasma GFAP over time in Aβ+ MCI compared to Aβ- (p<0.0001) and in subjects later diagnosed with AD compared to those that remained clinically stable (stable Aβ-:p<0.0001; stable Aβ+:p=0.049).
Conclusions
Plasma GFAP is strongly associated to Aβ status and is a good predictor of clinical evolution to AD.