Cortical laminar tau deposits and activated astrocytes in Alzheimer's disease visualised by 3H-THK5117 and 3H-deprenyl autoradiography

Hyperphosphorylated tau protein deposits and, inflammatory processes are characteristic components of Alzheimer disease (AD) pathology. We here aimed to visualize in vitro the distribution of tau deposits and activated astrocytes across the cortical layers in autopsy AD brain tissue using the radiotracers H-3-THK5117 and H-3-deprenyl. H-3-THK5117 and H-3-deprenyl autoradiographies were carried out on frozen brain sections from three AD patients and one healthy control. H-3-THK5117 showed a distinct laminar cortical binding similar to H-3-deprenyl autoradiography, with an extensive binding in the superficial and deep layers of the temporal neocortices, whereas the middle frontal gyrus showed an even binding throughout the layers. Globally, eventhough some differences could be observed, AT8 (tau) and GFAP (astrocyte) immunostaining showed a laminar pattern comparable to their corresponding radiotracers within each AD case. Some variability was observed between the AD cases reflecting differences in disease phenotype. The similar laminar cortical brain distribution of tau deposits and activated astrocytes supports the hypothesis of a close pathological interconnection. The difference in regional binding patterns of H-3-THK5117 and AT8 antibody staining suggest additional tau binding sites detectable by H-3-THK5117.