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SERUM GFAP DIFFERENTIATES ALZHEIMER´S DISEASE FROM FRONTOTEMPORAL DEMENTIA AND PREDICTS MCI TO DEMENTIA CONVERSION
Abstract
Aims
Reactive astrogliosis is a hallmark of Alzheimer´s disease (AD) and frontotemporal dementia (FTD) but differences between the diseases and time course are unclear. In this multicenter study including 610 individuals, we investigated whether serum levels of the astroglial marker GFAP are different in patients with AD dementia, MCI-AD and behavioural variant FTD (bvFTD).
Methods
The study included serum samples from patients diagnosed with AD dementia (n=230), mild cognitive impairment due to AD (MCI-AD, n=111), bvFTD (n=140) and controls (n= 129). A sub-group of MCI-AD (n=32) patients was longitudinally followed-up for 3.9±2.6 years after sample collection. Serum levels of GFAP, pTau181 and NfL were measured by Simoa (Quanterix) and Ella (ProteinSimple).
Results
In total, samples from 610 individuals from four clinical centers where investigated in this study. Serum GFAP levels in AD dementia were increased (median 375pg/mL, IQR 276-505pg/mL) compared with controls (167pg/mL, IQR 108-234pg/mL) and bvFTD (190pg/mL, IQR 134-298pg/mL, p<0.001). GFAP was already increased in the early disease phase (MCI-AD, 300pg/mL, IQR 232-433pg/mL, p<0.001) and was higher in MCI-AD patients who developed dementia during follow-up (360pg/mL, IQR 253-414pg/mL vs. 215pg/mL, IQR 111-266pg/mL, p<0.01, AUC=0.77). Diagnostic performance of serum GFAP for AD (AUC=0.84, sensitivity 98%, specificity 60%) was comparable to serum pTau181 (AUC=0.89, sensitivity 80%, specificity 87%) but superior to serum NfL (AUC=0.71, sensitivity 92%, specificity 49%).
Conclusions
Our data indicate a different type of reactive astrogliosis in AD and bvFTD and support serum GFAP as biomarker for differential diagnosis and prediction of MCI-to-dementia conversion.