Tracking reactive astrocytes in autosomal dominant Alzheimer disease with plasma GFAP and multi‐modal PET imaging

Background We have proposed astrogliosis as a “first wave” of response to AD pathology with diverging longitudinal changes reactive astrocytes and amyloid-β positron emission tomography (PET) retention in pre-symptomatic autosomal dominant (ADAD). It has been suggested that plasma glial fibrillary acidic protein (GFAP) could be marker neuroinflammation brain, although this hypothesis remains unproven. therefore compared GFAP levels 11C-deprenyl (DED) multi-modal PET design ADAD mutation carriers (MC) non-carriers (NC). Method Twenty-three individuals from families known mutations were included (MC = 9; NC 14). All underwent imaging 11C-DED, 11C-PIB 18F-FDG, for assessing monoamine oxidase B astrocytes, amyloid-beta deposition, glucose metabolism, respectively. Plasma sampling was performed after median 3 (interquartile range 1.5-5.5) months. measured using single molecule array technology. Eleven had follow-up investigations 2.7 2.5-2.9) years. Result binding increased significantly symptomatic stage while 11C-DED 18F-FDG uptake decreased towards estimated onset clinical symptoms MC. Cross-sectionally, showed negative correlations [18F]FDG widespread cortical areas, contrast no or binding. positive correlation uptake. Across the interval, four-fold greater intraindividual variation relative (longitudinal Δ variance 1.67 vs 0.39 z-scores, respectively). When averaging values tracer across consecutive time points same individual, strong found between uptake, but significant Conclusion Divergent brain may reflect different associated underlying processes, including types astrocytes. However, show large over assessment based solely on cross-sectional poses great challenges warrants further investigations.