Increased levels of GFAP and purinergic P2X7 receptor in Alzheimer’s disease brain are associated with Aβ, tau pathologies and synaptic loss

Astrogliosis plays an important role in Alzheimer’s disease(AD). We characterized glial fibrillary acidic protein(GFAP) and purinergic P2X7 receptor(P2X7R) alterations in AD and their associations with amyloid-β levels, tau pathology and synaptic density. Immunostaining(P2X7R, GFAP, amyloid-β, and phospho-tau) and autoradiography using [18F]JNJ-64413739 for P2X7R were performed in postmortem hippocampal and entorhinal cortex tissues from 42 AD patients and 35 nondemented-controls. Compared with nondemented-controls, AD hippocampi and the entorhinal cortex presented reactive astrocytes with increased GFAP and P2X7R levels. GFAP and P2X7R levels were positively correlated with amyloid-β, CERAD score, phospho-tau, and Braak stage and enriched around cored plaques. In conclusion, we found increased levels of GFAP and P2X7R in hippocampal and entorhinal cortex of AD patients compared with controls, associated with amyloid-β, tau, and Braak stage, highlighting the importance of astrogliosis in AD.